l r^ 1A if 11 ■ s. (jr A Reference Handbook OF THE MEDICAL SCIENCES EMBRACING THE ENTIRE RANGE OF SCIENTIFIC AND PRACTICAL MEDICINE AND ALLIED SCIENCE BY VARIOUS WRITERS FIRST AND SECOND EDITIONS EDITED BY ALBERT H. BUCK, M. D. THIRD EDITION COMPLETELY REVISED AND REWRITTEN Edited by THOMAS LATHROP STEDMAN, A. M., M. D. COMPLETE IN EIGHT VOLUMES VOLUME ONE ILLUSTRATED BY NUMEROUS CHROMOLITHOGRAPHS AND SIX HUNDRED AND ELEVEN FINE HALF-TONE AND WOOD ENGRAVINGS NEW YORK WILLIAM WOOD AND COMPANY MDCCCCXIII 5 Copyright, 1913 Bt WILLIAM WOOD AND COMPANY TIIE.MAIM.B. PRESS* YORK. PA PREFACE. A generation since a wise and far-seeing medical publisher, the late Mr. William H. S. Wood, and an accomplished medical editor, Dr. Albert II. Buck, conceived the happy idea of the Reference Handbook. There were at that time several "systems" covering special subjects in internal medicine and surgery, but none which satisfied the needs of the profession as a whole. It was to meet the want of a work of general information on all subjects relating to medicine in all its branches that this encyclopedia was designed, and how well it did so was evidenced by the cordial reception it received from the medical men of the country. The first volume, published in 1884, was followed at regular intervals by others until, in 1887, the eighth and final volume was delivered to the subscribers. In 1893 a supplementary volume covering the progress made in the preceding six years was published. During the years 1900-1904 a second edition of the work appeared, still under the management of Dr. Buck, and met with an equally favorable reception from the medical public. An Appendix, treating of Anaphylaxis, Opsonin Therapy, and other new subjects, was pub- lished, under the supervision of the present editor, in 1908. For a third edition of a work with this history of successful endeavcr behind it, no apology is called for, though a few words in the way of explanation may net be amiss. Dr. Buck, to whose rare editorial skill, aided by the loyal cooperation of over five hundred contributors, the success of the former editions was due, was reluctant to undertake the labor of seeing a third edition through the press, and the present editor, whose privilege it was to have assisted in the preparation of the first edition, was invited to assume the task. The general plan of the original work is followed in the present edition, but the editor has profited by the fact that the old plates have been destroyed to introduce some new features. The system of cross references has been largely extended and here and there these references have been amplified to full defini- tions or miniature treatises, in many cases thus affording all the information desired by the consulter without the necessity of searching through the main article. Considerable space has been given to the history of medicine, and in line with this, brief biographies of the leaders in medical thought and progress have been introduced. Most of these, signed A. H. B., have been contributed by Dr. Buck, who in this and many other ways has manifested his continued interest in the work. The series of amplified cross references on zoological subjects, signed A. S. P., have been written by Professor Arthur S. Pearse of the University of Wisconsin. The articles on the mineral springs of the United States in the second edition of the work were written by the late Dr. James K. Crook. These have been so thoroughly revised, in many cases entirely rewritten, by Dr. Emma E. Walker, that her name alone is signed to the articles. The thanks of the editor are due to the many contributors to the former editions of this work who have revised their articles, preserving the framework but rewriting them with the ripened experience of thirteen years of added work in their special lines. To those also who have contributed for the first time to this edition or have added to the number of their former contributions, the editor desires to express his gratitude for their prized assistance. And finally he wishes to record his obligation to the many friends who have aided him by suggestions of articles and of writers, and especially to Dr. Buck for encourage- ment and advice on many points. The Publishers, by their ready acceptance of his suggestions, sometimes involving greatly increased expense, have lightened his labors in no small measure. T. L. S. iii Authority to use for comment the Pharmacopeia of the United States of America, eighth decennial revision, in this volume, has been granted by the Board of Trustees of the United States Pharmacopeial Convention, which Board of Trustees is in no way responsible for the accuracy of any translations of the official weights and measures, or for any statement as to the strength of official preparations. LIST OF CONTRIBUTORS TO VOLUME I. LEONARD W. BACON, M.D., New Haven, Conn. Instructor in Operative Surgery, Medical Depart- ment, Yale University. JAMES B. BAIRD, M.D Atlanta, Ga. Formerly Professor of Clinical Medicine, Southern Medical College; Attending Physician, Grady Hospital. FRANK BAKER, M.D., Ph.D., Washington, D. C. Professor of Anatomy, Georgetown University School of Medicine, Washington, D. C; Supt., National Zoological Park, Smithsonian Institu- tion. EDWARD R. BALDWIN, M.D.. .Saranac Lake, N. Y. Assistant, Saranac Laboratory; Examiner, Adiron- dack Cottage Sanitarium; Director, Reception Hospital. WALTER A. BASTEDO, M.D.. .New York, N. Y. Associate in Pharmacology and Therapeutics, Columbia University; Assistant Attending Phy- sician, St. Luke's Hospital, New York; Consulting Physician, St. Vincent's Hospital, Staten Island; Fifth Vice President, National Convention for the Revision of the Pharmacopoeia. A. L. BENEDICT, A.M., M.D.. .. Buffalo, N. Y. Editor of The Buffalo Medical Journal; Consultant in Digestive Diseases, City and Columbus Hos- pitals; Attendant, Mercy Hospital; Author of "Golden Rules of Dietetics"; Charter Member of the American Gastroenterological Association. ROBERT PAYNE BIGELOW, Ph.D Boston. Assistant Professor of Zoology and Parasitology, Massachusetts Institute of Technology. ALBERT N. BLODGETT, M.D.. .. Boston, Mass. PERCIVAL R. BOLTON, M.D... New York, N. Y. Formerly Instructor in Surgery, Cornell University Medical College in New York City. JOHN T. BOWEN, M.D Boston, Mass. Edward Wigglesworth Professor of Dermatology, Emeritus, Harvard University; Chief of Service, Department, of Dermatology, Massachusetts General Hospital; Consulting Physician, Chil- dren's and Infants' Hospitals, Boston. ALBERT H. BUCK, M.D New York, N. Y. C. N. B. CAMAC, M.D New York, N. Y. Assistant Professor of Clinical Medicine, College of Physicians and Surgeons, Columbia University; Physician to New York City Hospital; Formerly Professor of Clinical Medicine, Cornell University Medical College in New York City. W. B. CANNON, A.M., M.D Boston, Mass. George Higginson Professor of Physiology, Harvard University. RAYMOND C. COBURN, M.A., M.D New York, N. Y. Anesthetist, City Hospital; Consulting Anesthetist, Beth Israel Hospital, New York City. BENSON AMBROSE COIIOE, B.A., M. B. (Tor.), Pittsburgh, Pa. Late Professor of Anatomy, LTniversity of Pitts- burgh; Associate Professor of Therapeutics, University of Pittsburgh; Attending Physician, St. Francis Hospital, Pittsburgh. THOMAS D. COLEMAN, A.M., M.D Augusta, ( i \. Professor of Principles and Practice of Medicine, Medical Department of the University of Georgia; Attending Physician, Augusta City and Lamar Hospitals. W. J. CONKLIN, M.D Dayton, O. Formerly Professor of Diseases of Children, Star- ling Medical College; Consulting Physician to St. Elizabeth's and Miami Valley Hospitals. LUZERNE COVILLE, M.D Ithaca, N. Y. Formerly Lecturer and Demonstrator in Anatomy, Cornell University at Ithaca. MONTGOMERY A. CROCKETT, M.D. . . Bedford City, Va. Formerly Adjunct Professor of Obstetrics and Gynecology, University of Buffalo Medical School. EDWARD CURTIS, M.D New York, N. Y. Late Emeritus Professor of Materia Medica and Therapeutics, College of Physicians and Surgeons, Columbia University. CHARLES TOWNSHEND DADE, M.D New York, N. Y. Consulting Dermatologist, Roosevelt Hospital, Englewood Hospital, N. J., and Vassar Brothers Hospital, Poughkeepsie, N. Y.; Dermatologist, St. Luke's Hospital Clinic. CHARLES L. DANA, M.D New York, N. Y. Professor of Diseases of the Nervous System, Cornell University Medical College in New York City; Physician to Bellevue Hospital; Neurologist to the Montefiore Homo; Ex-president N. Y. Academy of Medicine; President New York Psychiatrical Society. ROBERT H. S. DAWBARN, M.D. . .New York. Senior Attending Surgeon, City Hospital; Professor of Surgery, Fordham University Medical School; Emeritus Professor of Surgery, New York Polyclinic Medical School; Consulting Surgeon, New York Polyclinic Hospital. UEORGE V. N. DEARBORN, A.M., M.D., Ph.D., Boston, Mass. Professor of Physiology, Tufts Medical and Dental Schools, Boston; Professor of the Philosophy of Physical Education, Sargent Normal School, Cambridge; Author of "The Emotion of Joy," "A Textbook of Human Physiology," "Moto- sensory Development," etc. D. BRYSON DELAVAN, M.D. . .New York, N. Y. Professor of Laryngology, New York Polyclinic Medical School: Consulting Laryngologist, Gen- eral Memorial Hospital, Hospital for Ruptured and Crippled and Vassar Brothers Hospital, Poughkeepsie; Surgeon, New York Polyclinic; Consulting Physician, Stony Wold Sanatorium. LIST OF CONTRIBUTORS TO VOLUME I. FRANCIS X. DERCUM, M.D. .Philadelphia, Pa. Professor of Nervous and Mental Diseases, Jefferson Medical College; Consulting Neurologist to the Philadelphia General Hospital; Foreign Corre- sponding Member of the Neurological Society of Paris, and Corresponding Member of the Psychia- tric and Neurological Society of Vienna. WILLIAM A. NEWMAN DORLAND, M. D. . . .Chi- cago, III. Professor of Obstetrics, Medical Department, Loyoia University; Visiting Obstetrician, Cook County Hospital; Visiting Obstetrician and Gyne- cologist, Jefferson Park Hospital; First Lieu- tenant Medical Reserve Corps, U. S. A.; Member Committee on Nomenclature and Classification of Diseases of the American Medical Association. HENRY DUFFY, ESQ Baltimore, Md. Lately State's Attorney. ISADORE DYER, Ph.B., M.D. .New Orleans, La. Dean and Professor of Diseases of the Skin, Medical Department, Tulane University of Louisiana; Editor New Orleans Medical and Surgical Jour- nal, etc. R. G. ECCLES, M.D., Ph.D Brooklyn, N. Y. Ex-Dean Brooklyn College of Pharmacy; ex- Chairman Section of Active Principles of Com- mittee of Revision U. S. Pharmacopoeia. MAX EINHORN, M.D New York, N. Y. Professor of Medicine, New York Post-Graduate Medical School; Visiting Physician, German Hospital; Consulting Physician, White Plains and Hackensack Hospitals. GEORGE THOMSON ELLIOT, M.D..New York. Clinical Professor of Dermatology, Cornell Univer- sity Medical College in New York City; Consulting Dermatologist, St. Luke's, Columbus, and New York Lying-in Hospitals, and New York Eye and Ear Infirmary. LEONARD W. ELY, M.D Denver, Colo. Orthopedic Surgeon to the County, Children's, and St. Joseph's Hospitals. L. W. FAMULENER, M.D New York, N. Y. Assistant Director, Research Laboratory, Depart- ment of Health, New York City. FREDERICK G. FINLEY, M.D Montreal, Canada. Professor of Medicine, McGill University; Physician to the Montreal General Hospital. JOHN ADDISON FORDYCE, A.M., M.D New York, N. Y. Professor of Dermatology and Syphilology, The University and Bellevue Hospital Medical Col- lege; Visiting Dermatologist, City Hospital. WILLIAM WHITWORTH GANNETT, M.D.. Bos- ton, Mass. Formerly Instructor in Clinical Medicine, Harvard University Medical School. JOHN H. GIBBON, M.D Philadelphia, Pa. Professor of Surgery, Jefferson Medical College; Surgeon to the Pennsylvania and Bryn Mawr Hospitals; Consulting Surgeon to the Woman's Hospital. CHARLES L. GIBSON, M. D.. . .New York, N. Y. Adjunct Professor of Surgery, Cornell University; Surgeon to St. Luke's Hospital; Consulting Sur- geon to the City Hospital. A. II. CORDON, M.D Montreal, Canada. Demonstrator of Clinical Medicine, McGill Univer- sity; Out-patient Physician, Montreal General 11" ipital. JOHN GREEN, M.D St. Louis, Mo. Emeritus Professor of Ophthalmology, Medical Department of Washington University, St. Louis. ARTHUR R. GUERARD, M.A., B.S., M.D... Flat Rock, N. C. Formerly Instructor in Therapeutics, The Univer- sity and Bellevue Hospital Medical College, and Assistant Bacteriologist, New York City Health Department. LEWIS WENDELL HACKETT, M.D.... Boston. Assistant, Department of Preventive Medicine and Hygiene, Harvard Medical School. ALLAN McLANE HAMILTON, M.D., LL.D., F.R.S (Edin.), New York, N. Y. Consulting Neurologist to the Manhattan State Hospital for the Insane; Formerly Professor of Clinical Psychiatry at Cornell University Medical College and Consulting Neurologist to the Hos- pital for Ruptured and Crippled; Author of "A System of Legal Medicine." H. F. HANSELL, A.M., M.D.. .Philadelphia, Pa. Professor of Ophthalmology, Jefferson Medical College; Emeritus Professor Diseases of the Eye, Philadelphia Polyclinic; Attending Ophthal- mologist, Philadelphia General Hospital. WILLIAM A. HARDAWAY, M.D.. . St. Louis, Mo. Honorary Member of the American Dermatological Association. LUDVIG HEKTOEN, M.D Chicago, III. Director of the Memorial Institute for Infectious Diseases; Professor of Pathology, University of Chicago and Rush Medical College. FREDERICK P. HENRY, A.M., M.D Phila- delphia, Pa. Professor of the Principles and Practice of Medicine in the Women's Medical College of Pennsylvania; Attending Physician, Philadelphia Hospital; Consulting Physician, Woman's Hospital of Philadelphia. CHARLES ADAMS HOLDER, M.D Phila- delphia, Pa. Formerly Assistant in Therapeutics, Jefferson Medical College. JOHN HOWLAND, M.D Baltimore, Md. Professor of Pediatrics, Johns Hopkins University. JOHN B. HUBER, A.M., M.D..New York, N. Y. Professor of Pulmonary Diseases, Fordham Uni- versity Medical School; Visiting Physician, St. Joseph's Hospital for Consumptives. GEORGE THOMAS JACKSON, M.D New York, N. Y. Professor of Dermatology, College of Physicians and Surgeons, Columbia University; Consulting Dermatologist, Presbyterian Hospital and the New York Infirmary for Women and Children. SMITH ELY JELLIFFE, A.M., M.D., Ph.D. . .New York, N. Y. Professor Clinical Psychiatry, Fordham University; Adjunct Professor Diseases of the Nervous Sys- tem, Post-Graduate Medical School; Visiting Neu- rologist, City Hospital; Physician, Neurological Hospital, New York. JEFFERSON R. KEAN, M.D United States Army. Lieutenant-Colonel, Medical Corps, U. S. Army; Assistant to the Surgeon-General. OTTO KILIANI, M.D New York, N. Y. Professor of Clinical Surgery, Columbia University; Surgeon to the German Hospital. LIST OF CONTRIBUTORS TO VOLUME I. CHARLES LESTER LEONARD, M.D. .. .Phila- delphia, Pa. Professor of Roentgenology, Philadelphia Poly- clinic; Ex-President, American Roentgen Ray Society. J. F. LEYS, M.I) United States N wy. Formerly Superintendent Colon Hospital, Isthmian Canal Commission, and President Medical Asso- ciation of the Canal Zone. GEORGE BURGESS MAGRATH, M.D.. Boston. Formerly Assistant in Pathology, Harvard Uni- versity Medical School. MATTHEW D. MANN, M.D Buffalo, N. Y. Emeritus Professor of Obstetrics and Gynecology, Medical Department, University of Buffalo; Consulting Gynecologist, Buffalo General and Erie County Hospitals. CHARLES F. MARTIN, M.D. Montreal, Canada. Professor of Medicine and Clinical Medicine, McGill University; Physician Royal Victoria Hospital. PHILIP MARVEL. M.D Atlantic City, X. J. WILLY MEYER, M.D New Yobk, X. Y. Professor of Surgery, N. Y. Post-Graduate Medica School; Surgeon to the German and Post-Gradu- ate Hospitals; Consulting Surgeon, X. Y. Infir- mary for Women and Children, Skin and Cancer Hospital, Har Moriah Hospital, and Hospital for Deformities and Joint Diseases. BENJAMIN MICHAILOVSKY, B.S., M.D... New York, N. Y r . Deputy Physician, New York Hospital, O.P.D. T. WESLEY MILLS, M.A., M.D., L.R.C.P. (Lond.), London, England. Emeritus Professor of Physiology, McGill Univer- sity, Montreal, Canada. WILLIAM OLIVER MOORE, M.D., LL.B...New York, N. Y. Professor Emeritus of Diseases of the Eye and Ear, New York Post-Graduate Medical School; Oph- thalmic Surgeon to the Protestant Orphans' Home and Asylum; Consulting Ophthalmic Surgeon, Flushing Hospital. . Montreal, WILLIAM S. MORROW, M.D. Canada. EDWARD L. MUNSON, M.D United States Army. Major, Medical Corps, U. S. Army; Director, Field Service School for Medical < (fficers, Army Service Schools, Fort Leavenworth, Kansas. RICHARD COLE NEWTON, M.D Montclaih, N. J. Consulting Physician, Mountainside Hospital, Montclair; Member New Jersey State Board of Health. JOHN BENJAMIN NICHOLS, M.D Wash- ington, D. C. Lecturer on Dietetics, George Washington Uni- versity; Pathologist, Episcopal Hospital; At- tending Physician, Freedmen's Hospital. FREDERICK G. NOVY, Sc.D., M.D. Ann Arbor, Mich. Professor of Bacteriology and Director of the Hygienic Laboratory, University of Michigan. THOMAS A. OLNEY, M.D South Bend, Indiana. Surgeon to St. Joseph Hospital. I W.I VER T. OSBORNE, M.A., M.D New Haven, Conn. Professor of Therapeutics, Medical Department, Yale University; Member of the Revision Com- mittee of the United states Pharmacopoeia; Member of t he ( 'oiineil on Pharmacy and ( Ihemis- try of the American Medical Association. EDWARD 0. OTIS. M. D Boston, Mass, Professor of Pulmonary Diseases and Climatology, Tufts College Medical School; Late Visiting and Consulting Physician to the Massachusetts State Sanatorium; Ex-President, of the American Climatological Association; Physician to the Department of Tuberculosis of the Lungs, Boston Dispensary. WILLIAM H. PARK, M.D New York, N. Y. Professor of Bacteriology and Hygiene, The Uni- versity and Bellevue Hospital Medical College; Director of the Research Laboratories of the Department of Health of the City of New York. RICHARD MILLS PEARCE, M.D .. Philadelphia. Professor of Research Medicine, University of Pennsylvania. ARTHUR S. PEARSE, Ph.D Madison, Wis. Assistant Professor of Zoology, University of Wis- consin; Instructor in Zoology, Marine Biological Laboratory, Woods Hole, Mass. JULIUS POHLMAN, M.D Buffalo, N. Y. Late Professor of Physiology, Medical Department, University of Buffalo. SIOMUND POLLITZER, M.D..New York, N. Y. Professor of Dermatology, New York Post-Graduate Medical School; Physician to the German Dis- pensary, Class of Skin Diseases. EDWARD PREBLE, M.D New Y'ork, N. Y. ROBERT B. PREBLE, M.D Chicago, III. Professor of Medicine, Northwestern L T niversity Medical School; Attending Physician, Cook County and German Hospitals, Chicago. JOSEPH RANSOHOFF, M.D., F.R.C.S. (Eng.), Cincinnati, O. Professor of Surgery, University of Cincinnati. ANDREW ROSE ROBINSON, M.D.New York. Professor of Dermatology, New York Polyclinic; Attending Physician, New York Polyclinic Hospital; Consulting Dermatologist, Perth Amboy Hospital. HENRY H. RUSBY, M.D Newark, N. J. Dean and Professor of Botany, Physiology, and Materia Medica, New York College of Pharmacy; Pharmacognosist at the Port of New York for the U. S. Department of Agriculture; Chairman Scientific Directors, N. Y. Botanical Garden. T. E. SATTERTHWAITE, A.B., M.D., LL.D., Sc.D., New York, N. Y. Consulting Physician, Post-Graduate, Manhattan State, Orthopaedic, Babies', and Champlain Val- ley Hospitals; First Lieutenant, U. S. A. (Medical Reserve Corps). OTTO SCHULTZE, M.D New York, N. Y. Professor of Medicolegal Pathology and Assistant Professor of Pathological Anatomy, Cornell Uni- versity Medical College in New York City; Coro- ner's Physician in the Borough of Manhattan, New York City. R. J. E. SCOTT, M.D New York, N. Y. Formerly Gynecologist, Demilt Dispensary; and \i lending' Physician, Out-Patient Department, Bellevue Hospital, New York. vn LIST OF CONTRIBUTORS TO VOLUME I. FRANCIS J. SHEPHERD, M.D., LL.D., F.R.C.S. (Ed.), Montreal, Canada. Professor of Anatomy, Medical Department, McGill University; Senior Surgeon, The Montreal General Hospital; Consulting Surgeon to the Royal Victoria Hospital. J. G. SHERRILL, M.D Louisville, Ky. Professor of Surgery, University of Louisville; Visiting Surgeon, Louisville City Hospital. CHAXXING C. SIMMONS, M.D. .. Boston, Mass. Surgeon to Out-Patients, .Massachusetts General Hospital; Assistant in Surgery, Harvard Medical School. H. BEAUMONT SMALL, M.D . . Ottawa, Canada. Attending Physician, St. Luke's Hospital, Ottawa; Late Examiner in Materia Mediea, College of Physicians and Surgeons, Ontario. EDMOND SOUCHON, M.D... New Orleans, La. Formerly Professor of Anatomy and Clinical Sur- gery, Medical Department, Tulane University of Louisiana; Curator Souchon Museum of Anatomy. ALEXANDER SPINGARN, A.M., M.D.. Brook-. lyn, N. Y. Assistant Editor, Medical Record; Attending Pedi- atrist to the Bushwick and East Brooklyn and Jewish Hospital Dispensaries. HEIXRICH STERX, M.D New York, N. Y. Visiting Physician, St. Mark's Hospital and the .Methodist Deaconess' Home; Consulting Physi- cian, Methodist Episcopal (Seney) Hospital, Central Islip State Hospital, Portchester Hos- pital, and Glens Falls Hospital; Editor, Archives of Diagnosis. RALPH G. STILLMAN, M.D... New York, N. Y. Clinical Pathologist, Attending Physician for Con- tagious Diseases, First Deputy Attending Physi- cian to the Out-Patient Department, New York Hospital; Attending Physician, Seton Hospital; Instructor in Clinical Medicine, Cornell Univer- sity Medical College in New York City. LEWIS A. STIMSON, M.D., LL.D... New York. Professor of Surgery, Cornell University Medical College in New York City; Consulting Surgeon, New York and Bellevue Hospitals. E. W. TAYLOR, A.M., M.D Boston, Mass. Assistant Professor of Neurology, Harvard Medical School; Chief-of-Service, Neurological Depart- ment, Massachusetts General Hospital; Visiting Neurologist, Long Island Hospital, Boston. WILLIAM H. THOMSON, M.D New York. Visiting Physician, Roosevelt Hospital. PAUL THORNDYKE, M.D Boston, Mass. Surgeon-in-Chief, Boston City Hospital; Assistant Professor of Genito-Urinary Surgery Harvard Medical School. FRANK P. UNDERHILL, Ph.D., New Haven, Conn. Assistant Professor of Physiological Chemistry, Sheffield Scientific School of Yale University; Professor of Pathological Chemistry, Department of Medicine, Yale University; Chemist to the New Haven Hospital. CARL VON RUCK, M.D Asheville, N. C. Consulting Physician to the Winyah Sanatorium; Director of the von Ruck Research Laboratory for Tuberculosis. EMMA ELIZABETH WALKER, M.D New York, N. Y. Assistant Surgeon, Hospital for the Relief of the Ruptured and Crippled. HENRY BALDWIN WARD, Ph.D., Urbana, III. Professor of Zoology and Chief of the Research Laboratory of Parasitology, University of Illinois; Formerly Dean of the College of Medicine and Professor of Zoology, University of Nebraska, and Zoologist to the State Board" of Agriculture. JOHN COLLINS WARREN, M.D., LL.D., Hon. F.R.C.S., Boston, Mass. Professor of Surgery Emeritus, Harvard University Medical School; Consulting Surgeon, Massa- chusetts General Hospital. ALDRED SCOTT WARTHIN, Ph.D., M.D Ann Arbor, Mich. Professor of Pathology and Director of the Patho- logical Laboratories, University of Michigan. II. GIDEON WELLS, M.D Chicago, III. Associate Professor of Pathology, University of Chicago. WILLIAM A. WHITE, M.D., Washington, D. C. Superintendent, Government Hospital for the In- sane; Professor of Nervous and Mental Diseases, George Washington University Medical College and Georgetown University Medical College; Lecturer on Insanity, U. S. Army and U. S. Navy Medical Schools. H. AUGUSTUS WILSON, M.D... Philadelphia, Pa. Professor of Orthopedic Surgery, Jefferson Medical College; Orthopedic Surgeon to St. Agnes Hospital and to the Philadelphia General Hos- pital; Consulting Orthopedic Surgeon, Kensing- ton Hospital for Women and the Philadelphia Lying-in Charity. CHARLES F. WITHINGTON, M.D Boston. Visiting Physician, Boston City Hospital; Formerly Instructor in Clinical Medicine, Harvard Medical School. C. G. L. WOLF, B.A., M.D., CM., New York, N. Y. Formerly Instructor in Physiological Chemistry, Cornell University Medical College. JAMES HOMER WRIGHT, A.M., M.D., S.D., Bos- ton, Mass. Director of the Pathological Laboratory, Massa- chusetts General Hospital; Assistant Professorof Pathology, Harvard University Medical School. A REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aachen Abdomen Aachen. — See Aix-la-Chapelle. Abdomen, Surgical Anatomy of the. — Theabdomenis the region of the body lying between the thorax and the pelvis. It includes theabdominal wall, theabdominal cav- ity, and its contents, the latter comprising almost the whole of the digestive apparatus andapart of theurinary. Above, theabdominal \vallisseparated from the thorax by the costal arch. Below, it is continued into the pelvis and thighs, the line of separation on either side being the iliac crest (crista iliaca) laterally and Poupart's ligament (ligamentum inguinale) mesially. These superficial boundaries of the wall are not coextensive with those of the cavity, for it extends above into the vault of the diaphragm, corresponding superficially to the fourth intercostal space on the right side and the fifth on the left. Below, it passes into the pelvic cavity, the line of sep- aration between abdomen and pelvis being the linea iliopectinea. Here the lower limit is the upper surface of the levator ani and coccygeus muscles. The form and external appearance of the abdomen van- with sex. age, and the condition of the abdominal wall and underlying organs. In infancy, as the pelvis is undeveloped and the organs in the upper part of the cavity are relatively large, the abdomen is cone-shaped, the apex of the cone being directed downward. In adult males the region is cylindrical and slightly flattened from before backward. In females it is again cone-shaped, but the apex of the cone is above, as the diameter of the lower circumference of the thorax is always less than that of the pelvis. The abdominal wall presents anterolateral and posterior aspects. It differs from the walls of other cavities in being, for the most part, devoid of skeleton, which, with the elastic character of the tissues com- posing it, allows the cavity to vary in capacity accord- ing to the size of the contained viscera. At "all times it exerts upon them a gentle pressure, supporting them, and causing the more solid to impress the softer. This pressure may be appreciated in any laparotomy wound, when the omentum and more movable intes- tines are retained with difficulty. The anterolateral wall is composed of the following layers of tissue, which must be considered in detail: Skin, Superficial fascia {^^^ External oblique muscle, Internal oblique muscle, Transversalis muscle, Rectus muscle, Transversalis fascia, Preperitoneal tissue, Parietal peritoneum. In addition to this general description, certain regions which are commonly the seat of hernia must receive especial study. These are: The inguinal region, The inguinofemoral region. Vol. I.— 1 The Skin of the abdominal wall is thin and movable except in the region of the navel, where it is attached to the underlying tissue. Corresponding to the linea alba is a furrow which indicates the space between the recti muscles. Two transverse flexion folds are usually present, one at the level of the umbilicus, a second, one inch above the pubis. This latter marks the summit of the moderately distended bladder. In pregnancy, or during the growth of large intraabdominal tumors, the stretching of the skin may give rise to a series of longitudinal lines, called stria? gravidarum. Superficial Fascia. — Of this there are two layers. The superficial layer varies in thickness according to the amount of fat deposited in it. Both above and below- it is continuous with the corresponding layer of tissue in adjacent regions. In the pubic region it passes into the scrotum, losing the fat, and, joining the deep layer, it assists in the formation of the dartos. At the posterior border of the scrotum it becomes con- tinuous with the same layer of the perineum. The amount of fat deposited in this layer, together with that in the omentum and mesenteries, is the principal factor in determining the external appearance of the abdomen. Accordingly, all gradations occur, from the thin concave abdomen of the emaciated to the thick pendulous one of the obese. These variations become of importance in examinations of abdominal organs or in operations upon them. The thick wall renders the task more difficult. The deep layer is thin and more fibrous in structure. It can be separated distinctly only in the lower half of the wall; above, it is lost in the superficial layer. Below, externally, it is connected with the iliac crests: anteriorly, it passes over Poupart's ligaments, to be attached to the fascia lata half an inch below them. In the pubic region, together with the superficial layer it passes into the scrotum to form the dartos. At the posterior border of the scrotum the layers again separate, the deeper one forming the corresponding fascia of the perineum. This latter fascia is attached on each side to the rami of the pubis and ischium, and turning around the posterior border of the transverse perineal muscles, it becomes continuous with the deep perineal fascia. It is beneath this layer of tissue that urine or an infection is guided from the perineum through the scrotum upon the abdomen. The attach- ment of the fascia to the bony margin of the pelvis prevents the spread into the thighs on their inner sides, while the attachment to the fascia lata prevents a similar spread from in front. The deep superficial fascia is separated from the aponeurosis of the external oblique by loose areolar tissue except along the linea alba, where the attachment is more intimate. External Oblique Muscle (musculus obliquus externus abdominis) (Figs. 1 and 2). — This, the strongest and most superficial of the abdominal muscles, arises by fleshy digitations from the eight lower ribs, interdigi- tating in the upper half with the serratus magnus, in the lower with the latissimus dorsi. The fibers are Abdomen, Surscical Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ir: m I \ k Fig. 1. — On the Left Side, the External Oblique and the Anterior Layer of the Rectus Sheath are Removed; on the Right Side, the External and Internal Oblique and the Lower Half of the Rectus. The deep epigastric artery is shown through the wall. (Joessel.) a. Rectus abdominis; b, inseriptio tendinea; c, external oblique; d, linea alba; c, internal oblique; /, fascia transversalis; (7, internal abdominal ring; h, Poupart's ligament; £, anterior crural nerve; 3, femoral artery; k, femoral vein; I, spermatic cord;;m, fossa ovalis; n, deep epigastric artery, shown through abdominal wall; o, trans- versalis muscle; p, linea semilunaris; q, semilunar fold of Douglas. directed downward, forward, and inward, those from the last two ribs almost verti- cally downward to their insertion in the anterior two-thirds of the external lip of the iliac crest. The remaining fibers, more oblique in direction, terminate in a broad aponeurosis, which at the mid-line joins with the aponeurosis of the remaining muscles in the linea alba. The following structures in the aponeurosis of the external oblique re- quire especial mention: Poupart's Ligament (ligamentum in- guinale), formed by the thickened lower border of the aponeurosis, stretched be- tween the anterior superior iliac spine and the pubic spine. Attached to it below is the fascia lata, which gives to the ligament an outline, convex downward. The flexor mus- cles of the thigh, the femoral vessels, and the anterior crural nerve pass behind the ligament in their course downward. (iimli, ■nml's Ligament (ligamentum lacu- nare) (Fig. 5). — Reflected from the pubic end nf Poupart's ligament to the linea iliopec- tinea for about three-quarters of an inch, is a triangular layer of fibrous tissue termed Gimbernat's ligament. It has upper and lower free surfaces, and a concave external border, bounding the femoral ring internally. External Abdominal or Inguinal Ring (an- nulus inguinalis subcutaneus) (Fig. 2). — Situated in the lower and inner part of the aponeurosis is an oval opening, formed by the separation of the fibers composing this part of the aponeurosis from the fibers of m-t Poupart's ligament. The long axis of the ring corre- sponds in direction to that of the fibers of the aponeu- rosis. Its base is formed by the pubic crest, its sides by the diverging fibers, which are called the pillars of the ring. The superior or internal pillar, thin and flat, is attached to the anterior surface of the symphysis pubis, while the inferior or external, thick and pris- matic, essentially the inner end of Poupart's ligament, curves inward to terminate at the pubic spine. Further facts concerning the external ring will be mentioned in the special description of the inguinal region. Inter columnar Fascia (fibras intererurales). — Binding together the fibers of the aponeurosis above the inguinal opening is a set of fibers which arch trans- versely inward from the outer half of Poupart's liga- ment, thus closing the angular interval left between the diverging pillars. At the margins of the opening these fibers are continued over the spermatic cord and testicle as a fine fascia, the intercolumnar or spermatic fascia. Internal Oblique Muscle (musculus obliquus interims abdominis) (Fig. 1). — The general direction of the fibers composing this muscle is the opposite of that of the external oblique. It arises below from the outer half or two-thirds of Poupart's ligament, from the anterior two-thirds of the middle lip of the crest of the ilium, and from the lumbar fascia in the angle between the crest of the ilium and the outer border of the erector spinoe muscle. From this origin the fibers ascend over the side of the abdomen to be disposed of as follows: the most posterior fibers pass upward to be inserted into the outer surfaces of the three lower ribs; those from the crest anteriorly, the spine, and Poupart's ligament end in a broad aponeurosis which extends from the thorax to the pubis, and at the outer border of the rectus divides into two layers, to enclose this muscle, uniting again at the linea alba. The anterior layer is inseparably united with the aponeurosis of the external oblique, the posterior with that of the trans- versalis, and above with the seventh and eighth costal cartilages and the ensiform process. This arrangement obtains only in the upper two-thirds of the aponeurosis. Fig. 2. — On theLeftSide, the Aponeurosis of the External Oblique and the Course of the Deep Epigastric Artery on the Rear Surface of the Abdominal Wall are Shown; on the Right, the External Oblique is Removed, Opening the Inguinal Canal. (Joessel.) a, Poupart's ligament; 6, spermatic cord; c, anterior crural nerve; d, free edge of iliac portion of fascia lata; e, femoral artery;/, femoral vein; g, saphenous vein; Ji. fossa ovalis; i, reflected portion nf Gimbernat's ligament; /, fascia transversalis; /,-, lymph gland in femoral canal; I, fascia lata; m, pubic portion of fascia lata; n, cremaster muscle; o, internal oblique; p, external oblique; q, deep epigastric vessels; r, superior pillar of tin- external ring; s, inferior pillar of the external ring; t, inter- columar fascia. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES MmIoiikm, Surgical Anatomy In (he lower third there is no division into layers, l»>ih internal oblique and transversalis passing in front of the rectus wiih the external oblique. The deficiency resulting in the; sheath of the rectus is marked above by a semilunar edge, known as the semilunar fold of Douglas (linea semicircularis). The lowest fibers which arise from I'oupart's ligament arch downward and inward, and, joining similar libers from the transversalis, form the conjoined tendon of these two muscles, by which they are inserted into the anterior surface of the pubis and the inner part of the ilio- peetineal line, behind (iimbernat's ligament. The Transversalis Muscle (musculus transversus abdominis) (Fig. 1), situated beneath the internal oblique, arises from the inner surfaces of the six lower ribs, from the transverse processes of the lumbar vertebnE by an aponeurosis, and from the anterior two-thirds of the inner lip of the crest of the ilium. Passing horizontally inward, the fibers terminate in an aponeurosis about an inch external to the border of the rectus, except at the upper extremity, where the fibers pass behind the rectus al- most to the middle line. The arrange- ment of the aponeuro- sis was described with that of the internal oblique. Rectus Abdominis Muscle (musculus rec- tus abdominis) (Fig. 1). — This muscle con- sists of vertical fibers lying within the sheath formed by the internal oblique as described above. Situated on either side of the mid- line of the abdomen, it arises from the an- terior surface and crest of the pubis. Expand- ing and becoming thin- ner as it ascends, it is inserted into the carti- lages of the fifth, sixth, and seventh ribs, as well as the bone of the fifth. The fibers of the muscle are interrupted by three or more ten- dinous intersections (inscriptiones tendi- nece) placed, the first at the umbilicus, the second at the lower end of the ensiform process, the third midway between them. They are confined chiefly to its anterior fibers and are firmly united to the anterior wall of the muscle sheath. When additional transverse lines occur, they are usually incomplete and are placed below the umbilicus. The Linea Alba, formed by the union of the aponeu- roses of the two oblique and transverse muscles, extends in the mid-line from the ensiform process to the pubis. A little below the middle it is widened into a circular space, in the center of which is the umbilicus. Above the umbilicus the recti muscles diverge and the linea alba broadens. Below the umbilicus the recti muscles converge and the linea becomes narrower and passes in front of the conjoined inner heads of the recti muscles to the pubis. Passing from the linea, behind the conjoined heads, is a small band of longitudinal fibers, the adminiculum linea? alb*, which spreads out below into a triangular expansion attached to the upper border of the pubis behind the external head of the rectus. During pregnancy, or when the abdomen Fig. 3 — (Jurssi'l ) d, middle ff, bladder inguinal fossa; h, wis deferens; h t anterior crural nerve; l t iliac muscle; hypogastrica; o, plica urachi ; p, peritoneum. is distended by disease, the linea alba is much increased in breadth. The Linea Semilunaris, situated along the outer border of the rectus muscle, is a curved linear depre ton Corresponding to the narrow portion of the aponeurosis of the internal oblique, between the termination of the muscular liber- and tie- division of the aponeurosis to form the rectus sheath. Fascia Transversalis. — This thin layer of fascia lines the posterior surface of the transversalis muscle and is continued on to the under surface of the dia- phragm. Above the umbilical line it is exceedingly thin, but below, especially in the inguinal region, it is more strongly developed and is attached to I'oupart's ligament. Laterally, it is attached to the inner lip of the crest of the ilium and is continuous with the iliac fascia. An opening in the transversalis, the internal abdominal ring, will be described below. Preperitoneal Tissue and Parietal Peritoneum. — The properitoneal tissue is a variable layer which is situated between the transver- salis fascia and the peritoneum, and is more highly developed in the inguinal regions. Farther up on the ab- dominal wall it is fre- quently absent. In this layer are situated the most important blood-vessels of the abdominal wall. The parietal peritoneum will be more especially noted below. For the most part it is sepa- rated from the fascia transversalis by the properitoneal tissue, but along the linea alba and the umbilical region the two are united. Blood-vessels of the Anterior Abdominal Wall. — The Arteries of the abdominal wall are in two sets, superficial and deep. The super- ficial vessels are situ- ated in the superficial fascia. They are the superficial epigastric and the superficial circumflex iliac, de- rived from the femoral. The deep set comprises the six lower intercostals, the lumbar, the deep circumflex iliac, the superior epigas- tric, and the deep epigastric artery (arteria epigastrica inferior). Of these, the latter requires especial description. Arising from the distal end of the external iliac, the deep epigastric artery passes upward and inward across the rear wall of the inguinal canal to the posterior sur- face of the rectus; entering the sheath of the rectus it continues its course upward to anastomose with the superior epigastric, a branch of the internal mammary. It lies between the fascia transversalis and the parietal peritoneum in the properitoneal tissue. In the begin- ning of its course it encircles the lower and internal boundaries of the internal inguinal ring. Two small branches arise from the deep epigastric artery: the cremasteric, which accompanies the sper- matic cord, and the pubic branch, which ramifies on the superior surface of Gimbernat's ligament and the posterior surface of the pubic bone. On the surface of the abdomen the course of the artery may be indicated by a line drawn from the junction of the inner third Rear View of the Anterior Abdominal Wall in the Inguinal Region. a, Poupart's ligament; b, external inguinal fossa; c, femoral fossa; internal inguinal fossa; /, umbilical artery ; i, external iliac vein; ;, external iliac artery; plica epigastrica; plica Abdomen, Sureical Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES with the outer two-thirds of Poupart's ligament, obliquely upward to the umbilicus. The veins are likewise divisible into a superficial and a deep set. The superficial include the superficial epigastric, the superficial circumflex iliac, and the vena tegumentosa. The latter connects the axillary with either the superficial epigastric or the femoral veins. The deep veins accompany the corresponding arteries and are double. They anastomose with one another, and also with the superficial veins on one side and with the portal system on the other, through the para- umbilical veins which run in the falciform ligament of the liver. In pathological states which interfere with the circulation in either the vena cava inferior or the porta] system, the superficial veins may be much more prominent than is usual. In the former ease, the blood current is upward, toward the umbilicus, the veins assisting in the formation of a collateral circulation. In the latter case the current is downward, away from the umbil- icus, and the dilata- tion is due to direct stasis. Above the umbilicus the superficial lymph- atics empty into the axillary glands; below it, into the inguinal glands. The deep lymphatic vessels empty into the sternal glands above and into the iliac glands below. Nerves. — The ab- dominal muscles are supplied by the six lower intercostal nerves; the skin of the abdomen, by cutane- ous branches of the same together with the ilio-hypogastric and the ilio-inguinal from the first lumbar. The nerves are situated be- tween the transver- salis and the internal oblique, and pursue a, course corresponding to the intercostal space, from which they emerge as far as the sheath of the rec- tus, which they pierce to become cutaneous. Laterally, between the origins of the external oblique, the latissimus dorsi, and the serratus magnus, arises a series of lateral cutaneous branches which supply the skin of the lateral aspect of the abdomen. In this connection it is interesting to note the rela- tionship existing between the nerve supply of the abdominal wall on the one hand, and that of the abdom- inal viscera and peritoneum on the other. The viscera derive their principal nerve supply from the three splanchnics, which are formed by the union of the rami communicantcs of the six lower intercostals. Therefore the abdominal viscera and the abdominal walls are all connected with the same segments of the central nervous system. In disease these nerve connections may serve to explain many of the symptoms and signs, such as reflected pains and rigid abdominal muscles in acute inflammatory stairs. The surgeon is frequently called upon to open the Fig. 4. — Rear View of Anterior Abdominal Wall, the Peritoneum having been Removed. (Joessel.) a, Anterior crural nerve; b, external iliac artery; c, external iliac vein; d, obturator artery; e, obturator nerve; /, umbilical artery; q, ureter; h, seminal vesicle; 7, bladder; j, adminiculura linear alb®; k, vas deferens; I, spermatic vessels; m, transversalis fascia; n, iliacus; o, Poupart's ligament; p, semilunar fold of Douglas; q, obliterated umbilical arterv: r, urachus; s, suspensory ligament of liver; t, rectus muscle; u, deep epigastric vessels; v, internal abdominal ring. abdominal cavity through the anterolateral wall. The incisions should be carefully planned, first, to give ample room for the necessary intraabdominal manipu- lations; second, to do the least possible injury to the abdominal wall, thus reducing to a minimum the liability of a subsequent ventral hernia. The most common line of incision is through the linea alba, this route being chosen in most pelvic operations, in those upon the intestines in general, and in many of those upon the stomach. The line is easily followed above the umbilicus, where the linea alba is broad, but below, where it is narrow, the line is followed with difficulty. In incisions above the umbilicus the position of the falciform ligament of the liver should be remembered. Many surgeons prefer an incision slightly to one side of the linea — one which opens the sheath "of the rectus muscle and separates its fibers. They believe that such a wound heals more solidly than one s that divides the linea alba, formed as it is by the interlacement of numerous aponeu- rotic layers. Certainly the linea has but one possible advantage, that is, nonvascu- lar! ty. The rectus should be separated only in its inner half, because of the position of the nerve trunks in its outer half. For this reason a trans- verse incision will do less damage than a longitudinal one in the outer half of the rec- tus. In lateral incisions three points must be borne in mind: (l)The direction of muscular or aponeurotic fibers; (2) the course of nerves; (3) the course of blood-vessels. All longitudinal or oblique incisions will divide one or more layers of muscular fibers which, in many instances, it is impos- sible to avoid. How- ever, when possible the plan of McBurney should be followed — ■ namely, that of sepa- rating each aponeurotic layer in the direction of its fibers. When the fibers of all the layers cannot be separated in this manner, it is advisable to separate those of the external oblique and divide the remaining layers. The separation of the fibers possesses many advantages — it is almost bloodless, no large nerves are injured, and the edges of the wound, instead of tending to separate, tend to approximate. It has the dis- advantage of requiring a larger number of assistants and of not giving as free an opening as direct incision. When it becomes necessary to incise the entire thick- ness of the abdominal wall, the incision should be planned with due regard to the nerves, remembering that they are continued forward from the intercostal spaces between the transversalis and the internal oblique. For this reason, lateral longitudinal incisions along the rectus are objectionable, division of the nerves being followed by more or less paralysis, which is an REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdomen, Surgical Anatomy important predisposing factor in the development of a hernia. Transverse incisions in the lower abdominal region must avoid the deep epigastric artery the course of which is indicated above. In the upper half they must avoid the superior epigastric artery, which, however, i~ of less importance than the deep vessel. The inguinal region is bounded below by Pouparl 's ligament, internally by the median line indicated by the lineaalba, and above by a horizontal line extending from the anterior superior iliac spine to the median line. The tissue layers composing the wall are the same as those of the abdominal wall in general. Piercing the region in an oblique direction from behind forward, downward, and inward is the sper- matic cord (funiculus spermaticus) in the male and the round ligament (ligamentum teres uteri) in the female. The track which the spermatic cord pursues in the abdominal wall is known as the inguinal canal, but it must be understood that a true canal exists only in a pathological state. The canal presents for description an ex- ternal opening, an in- ternal opening, and four walls. As men- tioned, the external opening (annulus in- guinalis subcutaneus) is formed by the sepa- ration of the lower and the inner fibers of the aponeurosis of the ex- ternal oblique. The ring is closed by the intercolumnar fascia (libra' intercrurales) which is continued over the cord and testicle and must be teased from the cord before the ring is plainly visible. At the upper angle, it binds the columns to- gether, thus strength- ening the ring above. The externa! ring varies in size, depend- ing upon the develop- ment of the intercol- umnar fibers. Nor- mally, the opening will admit the end of the finger, but this is modified by the posi- tion of the body. ~ Fk:. 5. — On the Right Side arc Shown the Location and Relations of an External Inguinal Hernia; on the Left Side, those of a Femoral Hernia. The obturator artery is shown arising from the deep epigastric. Us course along the free edge of Gimbemat's ligament is diagrammatically shown on the left side. (Joessel.) a. Deep circumflex iliac artery; o, external iliac artery and vein; c, lymphatic glands; ) infundibuliform fascia; (4) the preperitoneal tissue and peritoneum composing the hernial sac. In Fig. 6. — Rear View of Internal Inguinal Hernia. (Joessel.) a, Rectus; 6, sac of internal inguinal hernia: c, bladder; d, vas deferens; e, seminal vesicle; f, obturator foramen; g, Poupart'g ligament; h, external iliac artery and vein; i, obliterated umbilical artery; ;', spermatic vessels; /.■, crural nerve; I, iliac muscle; m, deep circumflex iliac vessels; n, transversalis fascia; o, internal abdominal ring; p, deep epigastric vessels. congenital hernia this is the processus vaginalis perito- nei, and may be distinguished from the acquired peri- toneal coat by its relation to the testicle, the testicle being within the sac, and its firm adherence to the fascia propria. The acquired sac is easily separated from the fascia propria, while the congenital is separated with difficulty. The aci [uired hernial sac, like the congenital, lies directly in front of and in contact with the vessels of the spermatic cord, but does not pass below the testicle. Two additional forms of acquired external inguinal hernia are described, and though both are associated with incomplete obliteration of the processus vaginalis peritonei, they are not provided with a congenital sac. The first is the infantile variety, in which the processus vaginalis peritonei is obliterated only at the internal ring, leaving a large tunica vaginalis testis, behind which the newly formed hernial sac descends. In the second form, that of encysted hernia, the con- dition of the processus vaginalis peritonei is the same; but the septum which is undergoing obliteration yields, and, passing down into the tunica vaginalis testis, invests the new sac. In a dissection of the first, three layers of peritoneum must be divided; in a dissection of the latter only two, before the hernial contents are exposed. Internal inguinal hernia is of much less frequent occurrence and differs from the oblique variety, (1) in passing through the abdominal wall in the floor of the 6 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdomen, Surgical Anatomy middle or internal inguinal fossa, and consequently always lying on the inner side of the deep epigastric artery; ('-') in not passing along the entire canal; (3) in external appearance, being smaller and more globular in form; (4) in being situated over the os pubis and not in the course of the inguinal canal. The most valuable differential point is the position of the dee]) epigastric artery. The floor of the middle inguinal fossa is The rear wall of the inguinal canal. It is divisible into two parts: An inner part, the conjoined tendon of the inter- nal oblique and transversalis; an outer part, the trans- versalis fascia. The conjoined tendon (falx inguinalis) varies greatly in its development. In many cases it is slight and scarcely discernible, while in others it is strongly developed, especially in its deeper portion which is derived from the transversalis muscle, and which may bound the canal as far outward as the internal ring. There are two forms of internal hernia which pass out through the middle fossa. The first and most common form protrudes in the inner part of the fossa, either separating or pushing before it the conjoined tendon. It traverses only the lower end of the canal, to emerge at the external ring. The coverings of this variety, from within outward, are the peritoneum and subperi- toneal tissue, the fascia transversalis, and the conjoined tendon, except in those cases in which the sac passes between the fibers of the tendon, the intercolumnar fascia, the superficial fascia, and the skin. The sper- matic cord, placed behind and on the outer side, is not in contact with the sac, the cremasteric and the infun- dibuliform fascia being interposed. The second form of internal hernia passes into the inguinal canal through the outer portion of the rear _ wall, and lies between the conjoined tendon internally and the deep epigastric artery externally. It passes for a considerable distance along the canal, which gives it a certain degree of obliquity. The coverings of this hernia are the same as those of the first variety, with the exception of the conjoined tendon, which is replaced by a layer derived from the cremasteric fascia. The Inguinofemoral Region. — Upon removing the skin of the inguinofemoral region the superficial fascia of the thigh is exposed, ascending as a continuous layer upon the abdomen, descending upon the thighs, and internally passing into the dartos of the scrotum and the superficial fascia of the perineum. A deep layer of superficial fascia, thin and membranous, can also be distinguished. It is this layer which is attached to the margins of the saphenous opening, closing it and receiving in this locality the special name of cribriform fascia. Between the two layers are the superficial blood-vessels and the lymphatics of the thigh. The deep fascia of the thigh, the fascia lata, strong and aponeurotic, concerns us only in its anterior and upper regions, where it is described as consisting of two portions, the iliac and the pubic. The iliac portion, attached throughout to Poupart's ligament, lies in front of the femoral sheath, and, at the inner end of Poupart's ligament, terminates in a free edge, which, passing downward and outward and then inward, in the angle between the internal saphenous and femoral veins, becomes continuous with the pubic portion. The pubic portion, continued upward behind the femoral sheath to which it is attached, ends at the linea iliopectinea. Thus is formed the saphenous opening through which the internal saphenous vein passes to join the femoral vein. Its upper extremity lies about an inch external to the pubic spine. Its vertical diameter is about an inch and a half or two inches. Only the outer side of the opening is well marked, where the free edge of the iliac portion of the fascia forms a distinct falciform border, ending above and below in superior and inferior cornua. On the inner side, the pubic portion does not form a well-marked edge, but, after covering the pectineus muscle, passes upward behind the femoral sheath to which it is connected, to the linea iliopectiiH-a where ii is ci nit ii ii with the iliac fascia. The deep layer of the superficial fascia is attached to the margin of the opening which it closes, and, becau e it is perforated by the internal saphenous vein and numerous small arteries and veins, is known as the cribriform fascia. Poupart's Ligament (ligamentum inguinale). — The defect in the anterior wall of the pelvis between the anterior superior spine of the ilium and the spine of the pubis is bridged over by Poupart's ligament. The space between the ligament and the pelvic bones serves for the passage of certain structures from the abdomen into the thigh, and is divided into three compartments by the fascia 1 investing them. The first or iliac compartment, situated externally, is formed anteriorly by Poupart's ligament and the iliac fascia, posteriorly by the ilium, and internally is sepa- rated from the second or pectineal compartment by an intermuscular septum. This compartment transmits the iliopsoas muscle and anterior crural nerve. Fig. 7. — Rear View of Femoral Hernia, Showing Normal Obturator Artery. (Joessel.) a, Rectus muscle; b, transversalis fascia; c, deep circumflex iliac artery; d, deep epigastric artery; ft, cre- masteric artery; /, Poupart's ligament; g, pubic branch of deep epigastric; h, hernial sac; i, Gimbernat's ligament ; ;', pubic branch of obturator artery; k, abnormal obturator artery; I, obturator nerve; m, external iliac vein; n, external iliac artery: o, psoas muscle; p, anterior crural nerve; q, iliac muscle; r, iliac fascia. The second or pectineal compartment, lodging the upper end of the pectineus muscle, does not communi- cate with the abdomen, but corresponds to the space between the pubic portion of the fascia lata and the pectineal surface of the os pubis. The third or vascular compartment is the most important. It is situated in front of the other two, being bounded anteriorly by Poupart's ligament, and posteriorly by the continuous iliac and pectineal fascia?. It transmits into the thigh the external iliac vessels and the crural branch of the genitocrural nerve. Femoral Sheath. — As the external iliac vessels become the femoral, they are enclosed within the femoral or crural sheath, which accompanies them into the thigh. The anterior wall of the sheath is derived from the transversalis fascia, the posterior wall from the iliac fascia. On the outer side of the artery the two layers are continuous and closely embrace it; but on the inner side, while they are continuous, a space is left between them and the vein. Furthermore, both the anterior and posterior walls are attached to the iliac and pubic portions of the fascia lata, respectively. Within the sheath the artery lies external to the vein, and is separated from it by a thin septum stretched Abdomen, Surgical Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES from the anterior to the posterior wall. A second septum completes, on the inner side, the compartment for the vein, and cuts off a third space, about one-half inch in length, between the vein and the inner wall of the sheath. This is the funnel-shaped crural canal, through which a femoral hernia descends. Thus each vessel has its separate compartment, and there remains a small internal compartment containing only areolar and lymphatic tissue. The Femoral or Crural Canal (canalis femoralis). — The size of the femoral canal varies in different persons, being larger in the female than in the male. Like the external abdominal ring, the size of the femoral canal and the degree of tension of its orifices are markedly influenced by the position of the thigh. Extension, abduction, and external rotation contract the opening, while flexion, adduction, and internal rotation relax the femoral canal and its orifice; consequently this latter position should be used in the application of taxis to a femoral hernia. The four walls of this canal will be understood from the above description. Below, it terminates beneath the saphenous opening (fossa ovalis), while above, it opens on the anterior abdominal wall by an aperture known as the femoral or crural ring (annulus femoralis). This aperture is oval, and is larger in the female; its long diameter, directed transversely, is about one-half inch. The ring, covered by the parietal peritoneum, shows a slight depression, which, if not visible, can easily be felt. Beneath the peritoneum is a thin layer of con- densed properitoneal tissue, the septum crurale, which closes the ring. The ring is bounded anteriorly by Poupart's ligament and the deep crural arch; posteri- orly, by the os pubis, covered by the pectineus muscle and the pubic portion of the fascia lata; externally, by the external iliac vein. Internally to the ring are the sharp margins of Gimbernat's ligament, the con- joined tendon, and the deep femoral arch. With the exception of the external, the boundaries of the ring arc formed by very unyielding structures. Relations. — The position of the external iliac vein has been noted. The deep epigastric vessels cross the supe- rior and external angle. A small communicating branch between the deep epigastric and obturator arteries is usually found on the superior aspect of Gimbernat's ligament. Obturator Artery. — In two out of every five subjects, the obturator arises from the deep epigastric on one or both sides. It then turns backward into the pelvis to reach the thyroid foramen. In doing so it may pursue one of two courses: First, it may turn backward close to the external iliac vein, and will then be on the outer side of the femoral ring; second, it may first run inward, then arch backward along the free edga of Gimbernat's ligament, and will then be on the inner side of the ring. This inner position is more frequent in males than in females, though the epigastric origin on the whole is somewhat more common in females than in males. These anomalies can be detected in a given case only by palpation of the artery through the femoral canal. " Femoral hernia is rare as compared with the inguinal variety. It occurs more frequently in females, and is always acquired. Entering through the femoral ring, it passes vertically downward along the femoral canal as far as the end, carrying before it a sac of peritoneum and the septum crurale. Having reached this point, the hernia turns forward through the saphenous open- ins, where it derives a covering from the cribriform fascia, and then ascends beneath the superficial fascia of the groin as far as, or above, Poupart's ligament. The fascia propria is composed of the septum crurale and the femora] sheath, but at times, instead of dis- tending the sheath, it passes through an opening in it. Within the canal the hernia is small, as it is sur- rounded by unyielding structures; but having passed the saphenous opening, it rapidly enlarges. The direction of a femoral hernia and the position of the body should be borne in mind during attempts at reduction by taxis. Thus the lower limb should be flexed, adducted, and rotated inward. The pressure should be first downward, then backward, and finally upward. A femoral hernia may be strangulated at any part of the canal or at the saphenous opening, the most frequent point being the femoral ring. In all cases the stricture may be safely divided in an upward direction. At the femoral ring, the least damage will be done by dividing Gimbernat's ligament, except in cases of anomalous obturator artery. The coverings of a femoral hernia, from without inward, are the skin, the superficial fascia, the cribri- form fascia, the fascia propria, consisting of the femoral sheath and the septum crurale, and the peritoneum. The Posterior Abdominal Wall. — The posterior abdominal wall is of simpler construction and of less extent than the anterolateral. In its center is the portion of the spinal column composed of the five lum- bar vertebra with their connecting ligaments and carti- lages. On each side are arranged the muscles — ilio- psoas, quadratus lumborum, and erector spina 1 — enclosed within sheaths of fascia, that of the ilio- psoas muscle being of especial importance. This fascia is attached to the spinal column about the origin of the muscle; to the ligamentum arcuatum internum and to the anterior layer of the lumbar aponeurosis along the outer border of the muscle. Below, it firmly binds the iliac portion of the muscle into the false pelvis, being attached about its entire circum- ference, with the exception of the space where it passes beneath Poupart's ligament to form the posterior wall of the femoral sheath. It follows the tendon of the iliopsoas to its insertion, and ends by blending with the fascia lata. Beneath this fascia collections of pus resulting from caries of the spine or of the ilium may be guided into the thigh, to appear just below the groin on the outer side of the femoral vessels. These collections of purulent fluid should be distinguished from those situated beneath the transversalis fascia or in the subperitoneal tissue. In the first instance, the pus can spread no farther backward than the outer edge of the psoas, and no farther downward than the iliac crest and Poupart's ligament; internally, it is arrested at the mid-line. In the second instance, an abscess is in close contact with the cecum or sigmoid flexure, and may open into one of them; or it may follow the iliac blood-vessels into the thigh. In any case the typical picture may be lost should an abscess penetrate the layer of fascia beneath which it originally developed. The incisions through the posterior abdominal wall are made to expose the kidney and colon. They are noted in the article on Abdominal Organs. Thomas A. Olnet. Abdominal Injuries. — The abdominal viscera, un- like those of the cranium and thorax, are contained within a cavity whose walls are composed chiefly of soft tissues and to a relatively slight extent of bony and cartilaginous structures. The viscera of the upper abdomen are protected in some degree by the lower ribs and their cartilages, and those of the lower abdomen by the pelvic bones, while posteriorly there is the lumbar spine. The muscular wall of the abdomen, too, varies in thickness, and hence in its protecting properties, in different regions, being heavy and solid in the loins, and relatively thin at the sides and front. These defences are more apparent than real, for while viscera may be shielded by them from the effects of violence acting in certain directions, practically all the abdominal contents are exposed to violence acting from in front. The dangers of abdominal injuries depend also in no small measure upon the character of some of the viscera themselves. 8 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Injuries The gastrointestinal canal, although its mobility within the abdomen unquestionably enables it in many instances to escape the effects of violence, yet contains matter in a high degree infect ions, which, finding its way into the peritoneum, regularly excites a dangerous and usually fatal peritonitis. Distention of the hollow viscera also favors injury of them, for not only is there thus a larger mark for violence to act upon, but the increased tension of their walls facilitates the rupturing effect of violence. Others of the viscera, as the liver, spleen, kidney. and great vessels, are practically fixed and immovable, and therefore are subject to injury from a degree of violence sometimes comparatively slight. The abdominal walls are lined by, and the viscera wholly or partially covered by, the peritoneum. This membrane, by rendering the movements of the abdom- inal organs upon one another and beneath the abdom- inal walls easy, no doubt often facilitates their escape from the results of violence which would otherwise inevitably produce injury of them, and thus it be- comes a conservative agent. On the other hand, peritonitis, however produced, is the most dangerous and oftenest fatal of the 'con- sequences of abdominal injuries. Peritonitis developing as the consequence of inju- ries assumes one or other of three types. First, it results in the formation of adhesions between con- tiguous peritoneal surfaces, without pockets contain- ing fluid of any kind; or, second, the adhesions form pockets shutting in collections of pus of greater or less size. In both of these types the peritonitis is confined to some particular region of the abdomen and involves only a part of the peritoneum, the rest of it remaining uninflamed. Such types are distinctly conservative. In contrast to them there is a third type in which the inflammation, instead of being circumscribed, spreads quickly and soon involves the whole peritoneum. Such a type of peritonitis is usually fatal, while the first two are by no means necessarily so. Peritonitis is invariably the result of infection by pus-producing bacteria either from without, through lesions of the abdominal walls, or from within, through lesions of the viscera, particularly of the gastrointesti- nal canal. Why, in different instances, different forms of peritonitis are produced, does not as yet seem evident. We have not the means for determining what is the role of the peritoneal cells and other defensive factors in combating infection. Several facts are apparent, however. Numerous experiments and observations have shown that the development of peritonitis is greatly promoted by the presence of blood in the peritoneal cavity; it is known also that infection by the contents of the intestine high up is milder than when escape of the contents of the colon occurs; and, finally, it is known that small fecal extravasations may be encapsulated, while large ones are usually followed by a general peritonitis. Bile in moderate quantities may cause only an adhesive peritonitis; less frequently a general periton- itis follows. The same is true of perfectly normal urine; but decomposing urine, or urine containing inflammatory products or contaminated by unclean instruments — all of which are conditions implying the presence of bacteria — quickly excites a septic peritonitis. Abdominal Wall. — It is convenient to classify in- juries of the abdomen into two groups: (1) The sub- cutaneous, including contusions; (2) the open wound-. Subcutaneous injuries may be confined to the ab- dominal wall, or there may be lesions of the viscera also. The open injuries may be confined to the abdominal wall without penetrating it, or they may simply penetrate the abdomen without injuring any of the viscera, or there may be a prolapse or a wound of the viscera. Subcutaneous injuries of the abdominal wall result from the infliction of direct violence by blows, kicks, falls against, obstructions, spent balls, pas-age across the abdomen of wheels, crushing by machinery, etc. In this group, too, are included those cases of over- exertion in which muscles are ruptured. This acci- dent is api to occur in the recti, the diaphragm, or the elector spina', particularly in the presence of degenera- tive changes in these muscle Blood is extra vy ated bet ween the retracted ends of the muscle torn by overact ion or crushed by direct force; and after its absorption, repair occurs by cicatricial tissue, which may occasionally yield to intraabdominal pressure and become the site of hernia. Ecchymosis also occurs over wide areas beneath the skin or in the subserous connective tissue. Wounds of the abdominal wall which do not pene- trate are not in themselves peculiar injuries. With proper treatment they heal readily; but care must be exercised in the accurate approximation of the cut muscles to prevent the subsequent development of hernia. Another condition and one totally different pre- sents itself the moment the peritoneum is penetrated; then the wound becomes a grave injury, with the possibility of peritoneal infection and septic perito- nitis; but the dangers of such wounds depend upon their size, upon the implement by which they are inflicted, and upon the presence or absence of foreign bodies. Small wounds inflicted by narrow, sharp blades are relatively innocuous and are usually recovered from; the visceral peritoneum, especially the omentum, becomes adherent to the abdominal wall in the region of the wound, the general cavity is shut off, and heal- ing occurs without incident. In the case of larger wounds in which there is more or less gaping, or in those inflicted by dirty implements or complicated by the presence of foreign bodies, so great a surface of peritoneum is infected that no adequate adhesion occurs and a septic peritonitis follows. This may be prevented, however, in a certain proportion of cases at any rate, by proper wound treatment. Through wounds of the abdominal wall, even if of small or moderate size, and almost certainly through those of any considerable dimensions, prolapse of one or other viscus, or of parts of viscera, is apt to occur. The omentum is most apt to escape; next the small intestine; and, when separated from their attachments, parts of the liver and the whole or portions of the spleen and kidney have been known to undergo a prolapse. The viscus, especially if prolapsed through a small wound, soon becomes congested and edematous, and adherent at the margins of the wound; it may then remain fixed there, or become wholly or partly necrotic. Occasionally, as in the case of the omentum, the wound is plugged and permanently sealed; or a peritonitis spreads from the wound and destroys the patient's life. The dangers which prolapse of viscera thus adds to those inherent in the penetrating wound of the abdo- men, are the increased risk of peritonitis, unavoidable from the necessity of returning a prolapsed area of peritoneum almost certainly infected, and the likeli- hood of injury or of strangulation of the prolapsed viscera. The Liver and Its Ducts. — While the liver is protected within certain limits by its position beneath the ribs and their cartilages, its relative fixity renders traumatic lesions fairly frequent. Subcutaneous injuries are oftenest the result of crushing violence or of blows inflicted directly over the liver, and are not infrequently associated with fractures of the ribs, under which circumstances the bony fragments may be the agents by which the liver lesion is produced. Abdominal Injuries REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The lesion varies from slight subperitoneal lacera- tion to fissures of some depth and extent, or even pulpification of the affected region or separation of masses of liver tissue. The lesion occurs oftener in the right lobe than elsewhere. Open injuries of the liver are usually the result of bullet or stab wounds, and the lesion itself varies from a small puncture to a large incision or hole. In all these lesions, except those which are subperi- toneal, bleeding is free and often profuse, and consti- tutes the main danger to life. Healing of the injured liver tissue occurs readily; but it may be interfered with by infection conveyed by the blood current or introduced from without. The prognosis is modified in great measure by the presence or absence of associated injuries of other viscera. The mortality is reckoned by Edler at So. 7 per cent, for contusions, 55 per cent, for gunshot wounds, 04. S per cent, for stab wounds — average, 66.S per cent.; for uncomplicated injuries, 5-1.6 per cent. With or without injury of the liver itself the gall bladder or the ducts may be injured, and this may be followed by the escape of bile into the peritoneum in quantities more or less great. Peritonitis regularly follows, but there are on record a considerable number of cases which are exceptions. In them, in subcutaneous injuries, the extravasated bile has been encapsulated, and the patient has been saved by repeated aspirations; or the bile has escaped externally through fistuke formed in the tract of wounds, the flow gradually diminishing as these closed. Treatment of injuries of the liver is directed chiefly to the control of the bleeding from them, and ought not to be delayed if the symptoms of loss of blood are increasing. It should be undertaken before exsan- guination has proceeded far enough to make the addi- tional shock of the necessary operative procedures a source of serious danger. Hemorrhage from the liver may be stopped by gauze packing or by deep sutures; the cautery is useless. The liver and its ducts are most accessible through incisions of the abdominal wall, made parallel with the margin of the costal cartilages; but it may be necessary to cut through the latter, or even to approach the liver through the pleural cavity and diaphragm. Wounds of the gall-bladder are to be sutured; in only the rarest cases is extirpation indicated. Incom- plete divisions of any of the ducts should be closed as far as possible by suture, and in any case adequate provision for the escape of bile should be made by means of gauze packing. In a case of complete division of the common duct, if approximation of the severed ends by suture seems impracticable, anastomosis between the gall-bladder and intestine is clearly necessary. The Spleen. — The deep-seated position of the spleen in the abdomen makes injuries of this organ relatively rare. Its injuries are the result of much the same sorts of violence as produce lesions of the liver. OfEdler's 1 ICO cases, S3 were subcutaneous, 42 were bullet wounds, and 35 were stabs. It goes without saying that an enlarged spleen is much more liable to damage than one of normal size. The intimate relation of the spleen to other abdom- inal (and thoracic) viscera makes associated injuries of these organs of frequent occurrence. The great danger in injury of the spleen itself is from hemorrhage. Suppuration and abscess of the spleen have been known to follow even subcutaneous injuries of the organ. The prognosis is therefore grave. Of the subcu- taneous injuries, Edler e.-timates that S6.7 per cent, are fatal; of the shot, wounds, 83.3 per cent. The presence of associated injuries adds greatly to the dangers qf the situation and increases the mortality. The treatment of injuries of the spleen is chiefly directed to the control of hemorrhage. It should there- fore be carried out at the earliest possible moment. The spleen is easily reached through an incision carried from the free border of the costal cartilages vertically downward through the outer margin of the rectus muscle. For relatively small wounds or ruptures of the spleen deep sutures may be used to stop the bleed- ing, but for more extensive injuries one should proceed without delay to extirpation. _ The Kidneys and Ureters. — Contusions of the kidney may occur as the result of violence acting upon the loins in the form of kicks, blows, and falls. The lesion, in the mildest cases, consists in small subcap- sular lacerations or in more extensive tears, particu- larly at the bases of the pyramids, while in the most severe cases the kidney is ruptured, split into two or more fragments, or reduced to pulp. Lacerations without open wound are rare. [Bell 2 states that in the Royal Victoria Hospital, Montreal, 9,920 surgical cases were treated in the years 1903 to 1910, and among them were only seven cases of lacera- tion of the kidney without open wound.] Bleeding from the torn kidney tissue is apt to be profuse, and the extravasated blood infiltrates the retroperitoneal tissue or finds its way into the peri- toneum if rents of this membrane are also present. Wounds of the kidney are rare in civil practice, but they present in themselves no anatomical peculi- arities that distinguish them from the subcutaneous injuries. Repair of traumatic lesions of the kidney occurs with great readiness and completeness. Rarely, cysts persist at the site of injury or the kidney goes on to atrophy. < The danger to life in injury of the kidney lies first in the hemorrhage and then in suppuration. But the close relation of this organ to other viscera makes associated injuries of one or other of them of frequent occurrence, and thus the prognosis may be greatly modified. Of 10S cases of contusion of the kidney collected by Grawitz, 3 50, or 46.3 per cent.., were fatal. Of these 50 cases, IS were complicated by injury of more important viscera; in 17, suppuration occurred, with 7 deaths. Of the 32 uncomplicated cases, 14 died of the primary hemorrhage, S of secondary hemorrhage, 7 of suppuration, and 3 of urinary retention. Of 50 cases of stab wound of the kidney, 15 were complicated by injuries of other viscera, 35 were uncomplicated. Of the 35 uncomplicated cases, 11 patients died — 1 from primary bleeding, 1 from sec- ondary hemorrhage, 6 from suppurative nephritis of the injured kidney, 2 from suppuration of the uninjured kidney, 1 not stated. Of the 15 complicated cases, 3 were complicated by injury of the spine, and all were fatal; 1 by laceration of the peritoneum, fatal; 2 by injury of the liver, both patients died; 3 by injury of the intestine, 2 died; 6 by injury of the chest, 4 died; thus 12 died and 3 recovered. Of 50 bullet wounds of the kidney collected by Edler, 22 resulted fatally. Of the 50, but 20 were uncomplicated by injuries of other viscera, and of these only 3 were fatal. Injuries of the ureter occur infrequently, most often perhaps as accidents in operations upon the pelvic viscera. Extravasated urine collects behind the peritoneum, exciting a cellulitis there, or it enters the peritoneal cavity and produces a fatal peritonitis. The treatment of injuries of the kidney turns upon the control of bleeding, upon the provision for the escape of extravasated urine, and upon the avoidance of infection. In contusions, therefore, if catheterism is practised at all, it must be done with every care to avoid intro- ducing infection. For the less severe cases rest in bed is all that is required. For the more severe cases 10 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Injuries no delay is to be allowed in temporizing with urinary astringents, cold enemata, etc.; the kidney should be exposed and the bleeding controlled by suture, by gauze packing, or by partial or total nephrectomy. The external wound must be freely drained. The Bladder. — The position of the bladder behind the symphysis renders injuries of this viscus fairly infrequent. Whether the wound be subcutaneous or open, the presence of the peritoneum over a portion of the bladder wall is of capital importance, and it is convenient therefore to divide injuries of the bladder into two groups — extra- and intraperitoneal. Of the intraperitoneal injuries of the bladder, wounds may occur in any position, while the sub- cutaneous injuries or ruptures are usually transverse or oblique, of variable size, and occur oftenest Low down in the posterior wall, and least often at the summit. They are usually due to blows or falls upon the hypogastrium, especially when the bladder is distended and the abdominal walls are lax. There is free bleeding from the bladder lesion and escape of urine into the peritoneum; and sooner or later, generally within two or three days, a peritonitis is produced that, once established, has no tendency to remain circumscribed, but spreads and is regularly fatal. The promptness with which peritonitis devel- ops depends in great measure upon the character of the extravasated urine and upon the presence or absence of infection introduced from without by instrumentation. The extraperitoneal injuries occur in the anterior wall of the bladder, and vary in size from mere punc- tures to considerable rents. They are due to much the same sort of accidents that cause intraperitoneal injuries, and are not infrequently the result of fracture of the pubic bones, in which accident fragments are displaced and perforate the bladder wall. In these cases there is also free bleeding and an escape of urine into the cellular tissue of the prevesical space and into the subserous connective tissue; and, as a result of this, cellulitis develops in these tissues, and is practically always fatal. As to the relative frequency of extra- and intra- peritoneal ruptures of the bladder, the latter are much more numerous, being estimated by Fenwick* at SS per cent., as against 12 per cent, for the former. [Ferguson 5 states that of 109 cases collected from the literature, in only 49 was the rupture extraperitoneal.] The prognosis of injuries of the bladder, even if uncomplicated by injuries of other viscera, is always most grave. Bartel collected 504 cases with a general mortality of 45 per cent. Of these, 373 were extra- peritoneal, with a mortality of 20 per cent., and 131 intraperitoneal, with a mortality of 99.2 per cent. Arranged according to the presence or absence of an external wound, 169 eases were subcutaneous injuries and 90 per cent, died, while 335 were open injuries and 22.7 per cent. died. Of the 109 subcuta- neous injuries, 131 were intraperitoneal, with a mortality of 99.2 per cent.; 3S were extraperitoneal, with a mortality of 58 per cent. Of the 335 open injuries, 50 were stab wounds, with a mortality of 22 per cent. ; 285 were bullet wounds, with a mortality of 24.5 per cent. But these figures do not indicate the present mor- tality rate, which has undergone marked improve- ment with the advance of aseptic technic and the general adoption of earlier operative interference. Thus Schlange has collected 32 cases, with 15 deaths and 17 recoveries. Of these, 22 were intraperitoneal with 10 recoveries, and 10 extraperitoneal with 7 recoveries. The treatment of injuries of the bladder is designed to provide for the escape of urine and to close the bladder lesion itself, thus preventing infiltration of urine and the development of those inflammations which otherwise follow, and which are the immediate cause of death. Suprapubic cystotomy, then, should be done at the earliest moment possible. In extraperitoneal injuries the lesion should be closed by suture, wholly or in part, Retzius' space should be thoroughly drained by gauze (lacking, and the bladder itself should be drained by a perineal t ube. In a case of intraperitoneal injury the abdomen should be entered just above the bladder, and thor- oughly flushed, and the bladder itself should be closed by appropriate suture; a Mikulicz drain being passed into the depth of the pelvis and the bladder being drained by perineal tube. If the ureter has been severed the divided ends may be brought together by the method of Hochenegg or of Kelly, or the kidney may be removed. Implan- tation of the ureter into the intestine is a hazardous expedient, as is also implantation into the bladder. Tin; Gastrointestinal Tract. — Injuries of the stomach occur less often than those of the intestine, and injuries of the large intestine are less frequent than tliose of the small. They may be single or multiple. Such injuries vary in extent, being either incomplete (involving only one or two of the layers of the tract) or complete (involving all of them). The former group includes those cases in which the mucous membrane is lacerated by foreign bodies passing through the canal; those in which the intes- tinal wall is contused by violence acting from without, and in which the injury is accompanied by hemor- rhage between the component layers of the intestine, and those in which there is laceration of the peritoneal or peritoncomuscular layers. Such injuries are relatively unimportant. Per- foration may be a consequence but it probably occurs very infrequently. The complete lacerations are the important ones. They are of variable extent. In the stomach the lesion may be a minute perforation or a tear several inches in length; in the intestine also the injury may be a small puncture or a total trans- verse division of the bowel. There is more or less hemorrhage from the margins of the injured spot into the canal and into the peritoneum, and, most important, there is likely to be an escape of the con- tents of the intestine, the amount varying according to the dimensions of the opening. The consequence may be either a peritonitis of small and limited extent, resulting substantially in nothing more than adhesions; or a circumscribed peritonitis, with abscess of greater or less size; or a generalized septic peritonitis. In the smaller lesions, at least, extravasation of intestinal contents does not occur at once on the inflic- tion of the injury, for one commonly finds, in opera- tions done for bullet wounds of the intestine, that for some hours the opening is occupied and practically occluded by prolapsed mucous membrane. The mechanism of this occlusion was studied by Griffith, who found that in transverse wounds of one-third of an inch in length, the mucous membrane is extruded by the contraction of the longitudinal fibers of the intestine, and that in small longitudinal wounds the contraction of the circular fibers causes the margins of the wound to roll in, expresses the mucous mem- brane, and produces the same occlusion. Such ob- struction to the escape of intestinal contents is best seen in the small intestine, as it does not occur in the relatively thinner-walled parts of the colon. Injuries of the gastrointestinal tract result from contusions of the abdomen due to blows, falls, kicks, etc., which crush the intestine against the spine; arid if this part of the canal happens to be distended when the injury is inflicted, an actual bursting of its walls may result. Penetrating bullet and stab wounds of the abdomen are a common cause of injuries of the intestines, and the latter may also result from the passage of a foreign body through the intestinal tract. The prognosis is always grave and the chief danger is peritonitis. But the development of peritonitis 11 Alnl.iiniii.il Injuries REFERENCE HANDBOOK OF THE MEDICAL SCIENCES varies with the extent of the lesion, with the ability of the patient to circumscribe peritoneal infection by forming adhesions, and with the promptness with which surgical intervention is undertaken. According to Petry, of 199 cases of rupture of the intestine, 4.8 per cent, recovered through the develop- ment of adhesions to neighboring structures; in 8.5 per cent, a circumscribed fecal abscess formed. The general mortality of ruptures of the intestine was SG per cent.; of rupture of the stomach, 80 per cent. The seriousness of wounds of the gastrointestinal canal will appear more clearly when I state that they are specially apt to be multiple and that other organs an- apt to be w-ounded at the same time. Of 4,958 cases grouped by Coley,' the mortality was SI per cent. Of 105 cases treated bj r operation the mortal- ity was (17. 2 per cent.; and of these, 81 concerned the small intestine (mortality. 67.5 percent.) ; 24 the stom- ach (mortality, 75 per cent.); 36 the colon (mortality, 66.0 per cent.). The treatment should be undertaken at the earliest moment. But here there is not the positive indica- tion for instant operation that exists when the control of hemorrhage is the object in view. Nevertheless there should be no unnecessary delay in intervention, and the guide to the time of operation lies in the degree of shock present. The rule should be to operate the moment the general condition of the patient will admit of the procedures necessary, and before periton- itis has developed. In fact, after a peritonitis is under way and is spreading, no surgical measure is likely to be of avail in any but the most exceptional cases. The lesions are to be sought systematically, and any existing tears should be closed by some one of the recognized forms of intestinal suture; or the intestine should be resected, or anastomoses should be made. Then the neighboring peritoneum should be cleaned: or the entire peritoneal cavity should be flushed until it is perfectly clean ami then should be sponged dry. In most cases the judicious placing of gauze drains will be advantageous. The Mesentery axd Great Blood-vessels. — In- juries of these structures are exceedingly uncommon in subcutaneous injuries of the abdomen, but they occur with some frequency as the consequence of penc- trating wounds. The great danger entailed is from hemorrhage, which is considerable in wounds of the me 'ntery even of small size, while in those inflicted at the root of this structure or involving one or other of the named brandies of the aorta or vena cava, the bleeding is profuse and usually quickly fatal. Treatment, if available at all, is practically so only in those cases in which the wound involves the smaller vessels, which may be clamped and ligatured, or sur- rounded by suture, and so closed. Symptoms of Abdominal Injuries. — To arrive at the proper conclusion in estimating the consequences of abdominal injuries it is essential to study the in- dividual case from every point of view, beginning with the history of the injury itself, the degree of vio- lence exercised, the attitude of the patient at the time of the occurrence, and the state of his abdominal viscera — empty or full, normal or diseased. Tien, besides, one must note the sequence of symptoms, both the addition and the disappearance of local evi- dences, and the general condition of the individual considered as a whole. ()f the general symptoms, shock is apparent from the beginning in most cases of abdominal injury, although it varies in degree. It is most profound after severe contusions, and may be but slightly developed in a considerable number of cases of pene- trating wounds of the abdomen, so that the absence of very marked shock should not be construed to mean absence of visceral lesions of serious or even fatal character; although profound shock must usually be interpreted to be indicative of grave injury. The symptoms of hemorrhage are practically identical with those of shock, but they are gradually developed; and very often the similarity of the symp- toms of the two conditions makes their distinction impossible, at least with any degree of certainty. Peritonitis at its outset, which may occur within a few hours of the reception of an injury, sometimes closely resembles shock or hemorhage in its symp- toms, but when fully established it can hardly be mistaken for any other condition. There are certain local symptoms which appear after injuries of any of several viscera, and there are others which are peculiar to lesions of special viscera alone. Hemorrhage in any volume from the liver, spleen, or kidney — extraperitoneal or intraperitoneal — or from the mesentery, is accompanied by great pain, by distention of the abdomen, by great rigidity of its walls, by dulness in the flanks in some cases; but by no means all of these symptoms are present in every case in marked degree, and often one or more of them are absent altogether. The presence of gas in the peritoneal cavity is indi- cated by loss of liver dulness and by a peculiar, non- resistant feeling of the abdominal wall on palpation and percussion. Here, again, exceptions are numer- ous in both the positive and the negative sense. Per- forations of the intestine occur without loss of liver dulness, and liver dulness may be absent without per- foration of the intestine. Distention of the abdomen following injury is usually evidence of peritonitis. Pain is often experienced at the site of injur3 r , but is a better index of the location of injuries of the abdominal wall than of visceral injuries; it may be entirely absent or may be referred to another region, and is of little value in determining any of the features of visceral lesions. Tenderness, on the other hand, is of great value, and as a rule is felt only in the region injured, and is thus often an accurate guide to the location of the intraabdominal trouble. With injuries of the liver there is a history of wound or contusion in the region of the liver, followed by the local and general symptoms of hemorrhage. With injuries of the spleen there is a history of wound or contusion in the region of the spleen, followed by the local and general symptoms of hemorrhage. With injuries of the stomach there is a history of wound or contusion in the region of the stomach, or of the ingestion of a foreign body, followed by loss of liver dulness, by hematemesis, and by peritonitis. With injuries of the intestine there is a history of a wound or contusion of the abdomen followed by loss of liver dulness, by bloody stools in some cases, and by peritonitis. With injuries of the kidney there is a history of a wound or contusion in the region of the kidney, followed by evacuation of bloody urine, probably by tumefaction in the loin, and very often by the symp- toms of suppurative nephritis and perirenal cellulitis. With injuries of the bladder there is a history of a wound or contusion in the region of this organ. The symptoms and the conditions observed are the follow- ing: The bladder is very often, although not always, empty, and this condition is associated with apparent suppression of urine, with tenesmus, with evacuation of small amounts of blood through the catheter, with non-distensibility of the bladder by means of injec- tions or with the return of smaller volumes than those injected, and, finally, with perivesical cellulitis or with peritonitis. With injuries of the mesentery there is a history of a wound or contusion of the central region of the abdomen, followed by the local and general symp- toms of hemorrhage or of intestinal obstruction and peritonitis. 12 REFERENCE HANDBOOK OF Til 10 MEDICAL SCIENCES Abdominal Injuries Willi injury of any of the good-sized vessels of the abdomen there are the symptoms of hemorrhage. Diagnosis. — In most instances it is practically impossible to make a correct diagnosis of the viscera injured, and of the extent of the lesions present ill consequence of injuries of the abdomen. It com- paratively rarely happens that such injuries are confined to a single viscus, and in the combination of symptoms thai regularly ensue, some are over- shadowed by others. This fact, together with the unreliability of many of the symptoms which should be pathognomonic of special injuries, renders the diagnosis always one of probability. Nevertheless, in a considerable number of cases the lesions probably present may be estimated with a fair degree of accuracy, and in a small number the diagnosis may be made with certainty; but it should be emphasized that this number is small, and that in these particular cases the injuries present are relatively slight. All the factors possible must be duly considered: the character of the violence; its degree and the par- ticular region which it affects; the viscera present in this region and their condition at the time of injury ; and both the immediate and the later symptoms produced. To all of these features proper value must be assigned before the final conclusion can safely be formulated. Prognosis and Complications. — For the same reasons any statement in regard to the prognosis of abdominal injuries must be made with great caution. It may be said, however, that of those cases that re- cover after abdominal injuries, there are some in which the recovery is complete, and others in which it is incomplete (through the persistence of fistulas or of peritoneal adhesions, or through the development of hernia;). Of the complications of abdominal injuries, hemor- rhage is perhaps the most important. It may accom- pany almost any of the visceral injuries. Peritonitis is an almost equally grave complication. It is particularly apt to accompany injuries of the gastrointestinal tract, the bladder, and the biliary ducts. Later complications, as mentioned under prognosis, are: fistula? communicating with the alimentary canal, the biliary passages, and the kidney; adhesions which possibly give rise to functional disturbances of the viscera and especially to intestinal obstruction; herniae due to yielding of cicatrices of the abdominal wall; and, finally, the protrusion of one or other or several of the abdominal organs. Treatment. — The treatment of patients suffering from the results of abdominal injuries is of a twofold character: it comprises the treatment of the general symptoms — those of shock, hemorrhage, or peritonitis — and the treatment of the local lesions present. So far as the treatment of shock is concerned, the Eatient should be placed in bed and the foot of the ed should be elevated. He should be warmly covered, and artificial heat should be applied exter- nally by hot bottles, etc. Heart action is to be stimulated by the application of heat or mustard paste over the precordium, by subcutaneous in- jections of strychnine, of morphine, of atropine, or of whiskey, and by enemata of hot water, fluid extract of coffee, and whiskey. In many cases, and in those particularly in which the symptoms are due to hem- orrhage, the infusion of the patient with from forty to sixty ounces of physiological salt solution is of the greatest possible service; but it should be borne in mind that the effect of the infusion will subside in about four hours, and that then the injection may have to be repeated. All that it is necessary to say in this place in regard to the treatment of peritonitis has reference to its prevention, and this end is best served by the rigid observance of the rules which have been formulated for the aseptic or antiseptic treatment of wounds. In the ease of a wound of the abdominal wall, whether penetrating or not, the object of the local treatment is to secure union in the shortest time possible and in such a way that hernial protrusions are least, likely to OCCUT. For this purpose surgeons are fairly agreed that suturing must be done in layers, that is, thai identical structures in each margin of the wound are to !«■ united again; further, that such union is best accomplished by buried absorbable suture material, namely, catgut. But since catgul is absorbed within a few days, some other more enduring suture material must be used to preserve the apposition and beginning union, started between structures brought together by catgut. For this purpose, then, it is conventional to use deep suture-, embracing all the layers except the peritoneum, composed of silk, of silkworm gut, or of silver wire, Finally, accurate union along the skin incision is obtained by a continuous suture of fine silk. For subcutaneous injuries of the abdominal wall in which no rupture of muscle occurs, no special treat- ment is required beyond promoting the disappearance of extravasated blood by massage or aspiration. When rupture of muscle occurs the overlying skin is to be incised and the injury treated as a wound by successive tiers of sutures. When injury of one or of several of the abdominal viscera is certain or seems probable, no delay in instituting active treatment is permissible. It is far and away the better scheme to make explorative incisions through the abdominal wall, to render the diagnosis certain, than to subject the patient to the dangers of peritonitis or fatal exsanguination by waiting for a confirmation of the diagnosis of some doubtful or probable lesion by the development of positive symptoms. Many patients have without doubt been saved in consequence of this practice, and it is equally evident that many have been lost through hesitation in carrying out this scheme. There is little or no risk involved in the simple incision itself. But no operative procedure may be undertaken in states of profound shock or in cases in which the injuries are so extensive or so complicated as to make their treatment practically impossible; nor should interference be resorted to in the presence of well- marked peritonitis. On the other hand, in the pres- ence of a beginning peritonitis there still remains some possibility of success. If decided shock is present, energetic measures for its relief are called for, and only when the patient has begun to rally, that is, when the pulse becomes slower and stronger and the temperature begins to approach normal, may an operation be contemplated. The exception to this rule is met with in those cases in which the symptoms of apparent shock are due to hemorrhage. In such cases no substantial im- provement is likely to result from stimulation, and the patient's best if not only hope lies in immediate intervention, during which active stimulation should be carried on. For the treatment of any visceral lesion that is a consequence of a non-penetrating injury of the abdo- men it is necessary to incise the abdominal wall, the position, direction, and extent of the incision being determined by the viscus to be reached. To expose the liver and biliary ducts, an oblique incision parallel with the free border of the ribs, with its center about opposite the tenth cartilage, is con- ventional, while a similar incision on the left side exposes the stomach. But for either purpose a ver- tical incision through the outer part of the rectus downward, for variable distances from the free border of the ribs, serves equally well, and has the advantage that on the right side the kidney may be explored and attacked through it, while on the left side the spleen may also, if necessary, be reached. To expose the kidney by the transperitoneal route, 13 Abdominal Injuries REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the incision just described is the best; but for general purposes the Konig incision of the loin is much to be preferred in every way, since in itself it is extra- peritoneal, but at the same time it allows the perito- neal cavity to be entered very readily by extending the incision forward but a short distance. For the purpose of reaching the bladder an incision carried upward from the symphysis between the rectus muscles for the necessary distance, with the patient in the Trendelenburg position, exposes this organ perfectly; and, in order still further to enlarge the working space, the insertions of the recti into the symphysis may be divided for a short distance. Then, by the aid of retractors placed so as to draw the mar- gins of the wound apart, one may obtain a perfect view of the bladder, and ample room may be gained for any suturing operation. To gain access to the intestine and mesentery a median incision through the linea alba, of variable length and carried around the left side of the umbilicus will answer the purpose best. In this way the small intestine and mesentery, the rectum, and the sigmoid flexure may readily be reached, and by use of vigorous retraction the rest of the colon may be exposed, as well as the first and second parts of the duodenum. In making incisions through the abdominal wall, no time should be lost in using a director. The incision should be rapidly carried through the skin, the super- ficial and deep layers of fascia, and the muscles — clamps being applied to all bleeding points — until the transversalis fascia is reached. This is to be nicked with the knife and then divided along the length of the wound by scissors, thus exposing the peritoneum. The latter in turn is then to be pinched up by two pairs of forceps, a nick is to be made between them, and the membrane is then to be divided by scissors on a finger thrust beneath it through the small primary opening. It is optional whether bleeding points are to be tied before entering the cavity or whether clamps are to be left in situ. In the operative treatment of ■penetrating wounds of the abdominal wall it is best to enlarge the wound of entrance with the same precautions that are usually observed in formally opening the abdomen. Having done so, one should inspect the subjacent viscera, and then upon ascertaining the extent and character of the lesions to be treated, should, if necessary, make additional incisions through the abdominal wall in one or other of the positions, and in the manner just described, orthe wound should be still further enlarged. The treatment of the injuries of different viscera has been referred to under the description of their lesions. Here it is proper to indicate (he method of caring for prolapse of viscera, and for blood and foreign material which may be present in the peritoneal cavity. Almost any of the viscera, whether injured or not, may prolapse through wounds of the abdominal wall, and then be injured, or infected, or become strangu- lated; and the procedure to be adopted depends upon which of these events has occurred. In general terms, for purposes of treatment, it is always to be assumed that prolapsed viscera are infected; and whether a given viscus is to be returned or not will be decided by the possibility of rendering it practically aseptic or not, of repairing injuries pres- ent in it, or of restoring its circulation. Prolapsed omentum should in any case be tied off and removed. Prolapsed intestine, if strangulated, may be sutured in situ, or may be opened in such a manner as to form a fecal fistula which is to be closed subsequently, or it may be resected at once. If it has become in- fected it is to be subjected to very thorough mechan- ical cleansing with 0.5-per-cent. salt solution, and then returned after any injuries possibly present in it have been repaired. Prolapse of the spleen calls for its removal if stran- gulated or irreparably injured, or for its return if it can be thoroughly cleaned and repaired. Prolapsed portions of the liver are to be removed. Prolapse of the kidney should be managed by removal if it is necrotic or very greatly injured; by mechanical cleansing, repair, and replacement of the organ if it be possible. However, in any case ample drainage must be provided by gauze leading from the site of the returned viscus to the surface. Blood is to be completely removed from the ab- dominal cavity. This is done by scooping out clots with the hand and sponge, and by copious douch- ings with hot salt solution. Provision for subse- quent drainage need not necessarily be supplied. The entrance of foreign bodies from without or from the intestine, or the entrance of intestinal con- tents into the peritoneal cavity, is a fruitful source of peritonitis, and measures should be taken to pre- vent its occurrence. But once they have invaded the cavity and infected it, no time is to be lost in remov- ing them and in neutralizing their conseqences. Intestinal contents are to be removed by scooping and sponging, and then not only the visibly soiled areas of peritoneum must be cleansed by the liberal use of salt solution, but the same procedure must be carried out with regard to the whole peritoneum, especially if considerable quantities of foreign ma- terial have escaped; and, if necessary, evisceration must be resorted to. Drainage must of course be provided in every case. Drainage of areas of the peritoneum is best accom- plished by the use of gauze — ordinary absorbent gauze sterilized, or gauze impregnated with iodoform. Gauze has the advantage over tubes of various kinds in several respects. Besides the perfect manner in which it enables all exudate to be carried to the sur- face, it decidedly promotes the formation of adhesions about itself, and consequently about the region drained, which is often infected, and further oozing is best checked by the pressure exerted by the gauze packing. Gauze introduced for drainage purposes is used in ribbons, one or more of which are so placed as to lead from the area drained; or larger pieces of gauze may be packed into the region to be drained and brought out of the abdominal wound; or the Mikulicz dressing may be used. This consists of a piece of iodoform gauze about fifteen inches square, doubled back from its center like an umbrella, and containing strips of gauze so arranged that one after another can be withdrawn without disturbing the enveloping skirt, which is last to be removed. The period for withdrawing drains varies somewhat with the purpose for which they have been intro- duced; gauze placed to stop oozing should be removed in from twenty-four to forty-eight hours, while that used to drain infected or inflamed areas is allowed to remain in place some days longer. The treatment of the sequeUe of injuries, as fistula?, ventral hernia, etc., does not naturally come under the present title. Pebcival R. Bolton. References. 1. Edler: Langenbeck's Archiv, vol. xxxiv. 2. Bell: American Practice of Surgery, vol. viii, 1911. 3. Grawitz: Archiv fur klinische Chirurgie, No. 2, 18S7. ■1. Fenwick: Quoted in Traite de Chirurgie, Duplay et Reclus, vol. vii., p. 686. .">. Ferguson: American Practice of Surgery, vol. viii, 1911. 6. Bartel: Deutsche Chirurgie. Lieferung 52, p. 67. 7. Coley: Am. Journal of the Medical Sciences, March, IS91. Abdominal Organs, Regional and Surgical Anatomy of the. — The abdominal cavity is arbitrarily divided into nine regions by two horizontal and two vertical lines. The superior horizontal line extends between the cartilaginous ends of the tenth ribs, the inferior between the anterior superior iliac spines. These two lines divide the cavity into three zones, epigastric, 14 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Organs! Regional Anatomy nasogastric, and hypogastric, each of which is sub- divided into three regions by vertical lines passing upward from the ilio-pcctineal eminences to the higher horizontal line. The epigastric zone contains, in order, the right hypochondrium, epigastrium, and left hypochondrium. The nasogastric zone contains the right lumbar, umbilical, and left lumbar regions. The hypogastric zone contains the right iliac, hypogastric, and left iliac regions. The boundaries of I he several zones according to the B.N. A. nomenclature differ somewhat from those. The two may be compared by reference to Figs. S and 9. Fig. S. — Regions of the Abdomen in the Old Nomenclature. The viscera situated in each region are shown in the following table: Right Hypochon- Epigastrium. Left Hypochun- drium. drium. Liver. Liver. Stomach. Right kidney. Stomach. Spleen. Hepatic flexure. Gal] bladder. Left kidney. Colon. Duodenum. Splenic flexure. Pancreas. Colon. Right Lumbar. Umbilical. Left "Lumbar. Right kidney. Transverse colon. Small part of left Ascending colon. Duodenum and .small kidney. Ileum. intestines. Descending colon. < Ireat omentum. Small intestines. Right Iliac. Hypogastric. Left Iliac. Cecum. Small intestines. Sigmoid colon. Appendix. Bladder in children. Small intestines. Laal .oil of ileum. Distended bladder in adults. Pregnant uterus. Sigmoid colon. Liver (hepar). — The liver occupies the right hypo- chondriac region and part of the epigastric, and extends into the left hypochondriac region as far as the mam- millary line; at times it descends into the right lumbar region. With the exception of a small part of the right and left lobes, which come in contact with the anterior abdominal wall in the subcostal angle, it lies behind the ribs and costal cartilages. Surface Outline. — The outlil f the liver may be indicated on die surface of the body as follows: Supe- riorly, a line beginning in the mammillary line in the fifth lefl intercostal space, extending toward the right, through the lower end of the sternum, gradually rising to the fourth right interspace just inside the nipple line, then sloping downward behind the iifth and sixth ribs, where the superior surface is continuous with the right surface. Interiorly, beginning on the right side at the upper border of the third lumbar vertebra, the line runs directly to the costal arch, which it follows as far upward as the tip of the ninth costal cartilage. Here Fig. 9. — Regions of the Adbomen, in the Basle Anatomical Nomenclature. it crosses the subcostal angle to the eighth left cartilage, then gradually rises to terminate at the beginning of the superior line. The right surface, lying behind the seventh, eighth, ninth, and tenth ribs, is separated from them only by the thin edge of the lung, the diaphragm, and the pleura. It is thus apparent that I he lower border is most accessible to examination, and especially that part of it which lies across the subcostal angle. Here it usually reaches a point midway between the end of the sternum and the umbilicus. When the lower border in the remainder of its extent is easily palpable, the liver is either displaced or enlarged. The superior extent can be determined only by percussion, but the line of .absolute dulness does not correspond to the line above given, for the reason that the anterior, right, and posterior surfaces are considerably over- lapped by the lower edge of the lung. This line in the mid-line falls at the end of the sternum, in the right nipple line at the sixth rib, in the mid-axillary line at the eighth rib, and in the scapular line at the tenth rib. When the border of the liver can be palpated this method of determining its lower limit will be found more accurate than that by means of percussion. Relations. — The liver presents superior, anterior, pos- terior, inferior, and right surfaces. The superior surface is accurately moulded to the dia- phragm, which separates it from the pleura?, lungs, peri- cardium, and heart. The anterior surface, also in contact with the dia- phragm, with the exception of the small region coming in contact with the abdominal wall in the subcostal 15 Abdominal Organs, Regional Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES angle, lies behind the fifth to the ninth costal cartilages and adjacent portions of the ribs. In its upper part it is overlapped by the lower margin of the lung. The posterior surface, also in contact with the dia- phragm and overlapped by the lung, covers in turn the right suprarenal capsule, the vena cava, the thoracic duct, and the esophagus. The inferior surface is plainly impressed by the fol- lowing organs: Beginning at the right, in front, the hepatic flexure of the colon; behind, the right kidney, immediately to the left of which is the impression of the duodenum, and to the left of both the impression of the gall bladder. The succeeding part of the liver is the quadrate lobe, lying in front of the lesser omentum. Finally, the under surface of the left lobe overlaps the lesser curvature and upper part of the anterior surface of the stomach. Regions of the Abdomen, Posterior View. (Joessel.) The right surface lies internal to the seventh, eighth, ninth, tenth, and eleventh ribs, being separated from them by the diaphragm, and being overlapped above by the lung. Many clinical facts of importance can be learned by a close study of these relations. In gunshot and stab wounds of the lower part of the thoracic wall, lung, pleura, diaphragm, peritoneum, and liver may all be involved. The end of a fractured rib may penetrate the liver. Abscesses of the liver may extend through the diaphragm and open into the pleural cavity, or, u hen this is obliterated by adhesions, into the lung, and a bronchus. Behind, an enlargement of tne liver may retard the circulation in the aorta, the vena cava, or the thoracic duel. Below, the close relations of the stom- ach, duodenum, and colon explain the ease with which adhesions develop between these organs, and disease spreads from one to the others. 16 During inspiration, the liver descends about the breadth of one intercostal space. The lower border is more easily palpable in the erect posture than in the recumbent, as in the latter it recedes somewhat behind the costal arch. These changes in position, especially the first, may serve to distinguish a tumor or swelling of the liver from one of the stomach, kidney, adrenal gland, or pancreas. The peritoneal relations of the liver are extensive and important. For the most part its surface looks into the general peritoneal cavity, and the reflec- tions of the peritoneum from the abdominal wall and diaphragm are the principal agents in supporting, or rather suspending, the organ. A small part of its posterior surface is not visible from the greater cavity, as it looks into the lesser. This corresponds in extent to the Spigelian lobe. A second area of the posterior surface, between the layers of the right coronary liga- ments, is not covered by peritoneum; it lies in contact with the diaphragm. This locality is the favorite seat of subphrenic abscesses, and here they most easily spread to the pleura and lung. Blood-vessels. — The artery of the liver is the hepatic branch of the celiac axis. It reaches the organ be- tween the layers of the lesser omentum, and entering at the transverse fissure its branches accompany those of the portal vein. The portal vein, formed behind the head of the pan- creas by the union of the superior mesenteric, splenic, inferior mesenteric, and the veins of the stomach, also ascends in the lesser omentum to the transverse fissure. In the substance of the liver its branches are situated within the portal spaces, i.e. outside the lobules, before entering the intralobular capillaries. They are dis- tinguished by their relatively thick walls and collapsed state on cross section. An infective thrombophlebitis in a distant part of the abdomen or pelvis may be fol- lowed by a metastatic abscess or abscesses in the liver, a phenomenon explained by the anatomy of the portal circulation. The hepatic veins are remarkable for their thin walls, which, closely connected with the surrounding liver substance, stand widely open on section. Consequently a rupture or incised wound of the liver bleeds with great freedom and the bleeding has little tendency to cease spontaneously. The hepatic veins emerge on the posterior surface of the liver, entering immediately the inferior vena cava within half an inch to an inch "from its termination in the right auricle. They have no valves; consequently the circulation in them is easily impeded. In some forms of valvular heart lesions — e.g. tricuspid insufficiency — the pulsation of the heart may be transmitted through them to the liver. The excretory apparatus of the liver consists of the hepatic duct (ductus hepaticus), the cystic duct (ductus eysticus), and gall bladder (vesica fellea), and the common duct (ductus choledochus). The gall bladder, three or four inches in length and with a capacity of from one to two ounces, is held in position on the under surface of the liver by the peritoneum. As a rule, it is closely applied to the liver substance, lying in a dis- tinct fossa; but it may hang free, completely invested by peritoneum and suspended by a mesentery. Its fundus projects beyond the lower border of the liver opposite the ninth costal cartilage. It is directed downward, forward, and to the right, while the neck is in the opposite direction. Immediately below it are the transverse colon, duodenum, and sometimes the pylorus of the stomach. The relation to the colon is most constant and important. An artificial opening is sometimes formed between the two organs, and through it gall stones may be passed. The ducts are all situated between the layers of the lesser omentum, and can be easily exposed by removal of its anterior layer. The portal vein, hepatic artery and hepatic nerves are found in the same space, but the ducts are anterior to them, and occupy the right free edge of the omentum. In making a dissection, or in an operation, the foramen of Winslow should first be UJ m iu u z LU < o Q UJ to c E o TJ JD < 0) .c +-J >♦- o V) c o +-> ro +■> > t_ TJ ID O sz CD o CD c CD +j CO M— r u o J* o c -M 3 (/) l- c en 0) O) JC c- +■> O H- o o ^^ o o m en o b .c b T! (U C O) CO CO TJ (0 5 > t_ 01 CD DC TJ C (0 ■♦■" c o REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Organs, Regional Anatomy located, and, with the fingers of the left hand in it for a guide, an exposure can be easily accomplished. The cystic duct, arising at the neck of the gall bladder, is an inch and a half in length. It is directed downward, backward, and to the left, to join the hepatic duct at an acute angle. The hepatic duct, about two inches in length, is directed downward, backward, and to the right. It arises at the liver by two main branches. The common bile duct, formed by the union of these two, continues the direction of the hepatic along the right free edge of the lesser omentum on the anterior surface of the portal vein, and to the right of the hepatic artery. Approaching the duodenum, the vein tends to the left, the duct to the right. This relation of the vein to the duct is remarkably constant, but the hepatic artery and its branches are subject to frequent varia- tions which should be guarded against. As the com- mon duct reaches the duodenum, it passes behind its first portion, then downward, between the second por- tion and the head of the pancreas; or it is embedded in the latter, from which point onward it accompanies the pancreatic duct into the lower part of the second por- tion of the duodenum. The duodenal orifice is mark- edly constricted, but just proximal to it the duct is dilated, forming a well-marked diverticulum. Conse- quently a calculus may successfully pass the entire duct, to be arrested at the terminal orifice. To cause a jaundice, calculi must be situated in either the hepatic or the common duct, for any number may occupy the gall-bladder or the cystic duct, yet give rise to few or no symptoms as long as they remain there and the gall bladder is not infected. Not all cases of obstructive jaundice are due to gallstones. Enlarged lymphatic glands in the lesser omentum, tumors of adjacent organs, especially of the head of the pancreas, hydatids, ascaris, adhesions producing flexures of the ducts, and many other causes have been noted. Stomach (ventrieulus). — This varies in position and relations according to the degree of distention. When empty, it lies in the left hypochondrium and left half of the epigastrium, the cardiac orifice being four to five inches posterior to the interval between the seventh left costal cartilage and the ensiform process, on a level with the eleventh or twelfth dorsal vertebra. This is the most fixed portion of the stomach, and participates only slightly in any changes of position. The pylorus is in or near the mid-line, at the level of the last dorsal or first lumbar vertebra. It looks toward the right, and is the most movable portion of the stomach. Thus a tumor of the pylorus may be found in the central or lower part of the abdomen. The anterior and posterior surfaces are separated by sharp borders, and the entire viscus recedes from the anterior abdominal wall behind the liver. When distended, the fundus fills the left cupola of the diaphragm, impinging upon the liver and heart. The great curvature comes in contact with the anterior abdominal wall in the subcostal angle, and may enter the left lumbar and umbilical regions. Immediately below it is the transverse colon. The pylorus moves to the right as much as two or three inches, and rotates so that it is directed backward, being concealed from in front by the dilated lesser cul-de-sac. Relations. — The anterior surface is divisible into two regions; the upper and right region, which includes the pylorus and cardia, and is overlapped by the right and left lobes of the liver; and the lower and left region, which may be subdivided into two, viz., the small triangular portion in contact with the anterior abdominal wall, and above this the portion lying behind the costal arch and diaphragm. The fundus is also overlapped by the lung and pleura in the fifth and sixth intercostal spaces. Here, again, a wound may involve both thoracic and abdominal viscera. Posteriorly, the stomach is in relation with the diaphragm, spleen, left kidney and capsule, pancreas, and the splenic flexure of the colon, all of which taken together form for it a concave bed. The peritoneal relations of the stomach are compli- cated. Its anterior surface faces the greater peritoneal cavity, but the posterior surface is concealed behind the great oment uin, which hangs from its greater curva- ture. Furthermore, joined to the posterior surface of the omentum are the transverse colon and the meso- colon. When the omentum is raised these structures are carried with it. Only by passing the finger through the foramen of Winslow can the posterior surface of the stomach be reached. In a dissection, however, one of two routes may be chosen. The first lies between the greater curvature and the transverse colon; the second passes through the transverse mesocolon. A periton- itis arising from perforation of the posterior wall of the stomach, whether due to trauma or to disease, will at first involve the lesser cavity only and may be limited entirely to it. In operating for wounds of the stomach, the posterior surface should always be examined in the manner indicated. The lesser omentum is attached to the entire lesser curvature, while the gastrosplenic and gn ■: 1 1 er omenta are continued from the greater curvature. The arteries of the stomach are derived from the three branches of the celiac axis, and reach the organ between the layers of the omenta. On the lesser curvature an inch is formed by the gastric and pyloric branches of the hepatic; on the greater, a similar arch is formed by the gastroepiploica dextra and sinistra. From these arches transversely directed branches arise which anastomose near the center of the surfaces. Incisions in the stom- ach wall are best made in the direction of the transverse branches, with the exception of the central region where the sets anastomose. Small Intestine (intestinum tenue). — With the ex- ception of the duodenum, the small intestines are sur- rounded throughout by peritoneum, and are suspended from the posterior abdominal wall by a mesentery. The line of attachment of the mesentery extends from the left side of the second lumbar vertebra obliquely across the vertebral column, aorta, vena cava, and third portion of the duodenum to the right sacroiliac articula- tion. Although this line is only six or eight inches in length, and the average width of the mesentery is eight or ten inches, it reaches at its convex intestinal edge a length of some twenty feet. The middle or lower intestinal loops have the widest mesentery and are therefore most likely to enter a hernia. Between the layers of the mesentery are the blood-vessels, lymph- atics, and nerves of the intestine. The duodenum is for the most part situated behind the peritoneum, a position which it acquired when the large intestine of the embryo crossed the small. Up to this time it possessed a mesentery, which then fused with the posterior body wall. The first portion of the duodenum is movable except at its distal end. With an empty stomach it is directed transversely; with a distended stomach, anteroposteriorly. Above, it is in relation with the liver and gall bladder; below, with the pancreas; behind, with the portal vein and common bile duct. Beneath the neck of the gall bladder, at a point opposite the first lumbar vertebra, it turns downward as far as the fourth vertebra, in front of the right kidney and vena cava, being crossed anteriorly by the meso- colon, above and below which it is covered by visceral peritoneum. Internally is the head of the pancreas, whose duct opens with the bile duct into the lower portion of the duodenum. This constitutes the second portion, at the end of which the duodenum turns to the left across the spinal column and great vessels to ascend a short distance and end in the jejunum opposite the first or second lumbar vertebra. Note its relations to surrounding organs in connection with the spread of disease. It may be involved and the peri- toneal cavity may escape. Wounds are serious because of its inaccessibility and its fixed position. With the exception of the first part, it cannot be raised into a laparotomy wound. Its arteries, forming an arch within the concavity, may be opened in a duodenal ulcer and may allow a fatal hemorrhage. The jejunum and ileum include the remainder of the Vol. 1—2 17 Abdominal Organs, Regional Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES small intestine, called intestinum tenue mesenterfale — two-fifths jejunum, three-fifths ileum. Although there is no distinct line separating them, each has distinctive characteristics. The walls of the jejunum are thicker and more vascular, the valvulae conniventes are numerous and perfectly developed, and the caliber is greater. Peyer's patches are larger and more numer- ous in the ileum. The coils of the small intestines have no fixed position, but one may expect to find jejunum in the umbilical, left lumbar, and left iliac regions, while the ileum tends more to the right side, toward the hypogastric region and toward the pelvis. Because of their wide extent and exposed position the small intestines are frequently injured. The degree of injury may vary from slight contusion to complete rupture, and is greater the nearer it ap- proaches the stomach and the more distended the coils happen to b». The extent to which the abdominal wall is injured does not indicate the severity of the visceral injury, for the most extensive laceration may follow a blow which scarcely leaves a mark upon the skin. The great dangers are hemorrhage and fecal extravasation, especially the latter. It occurs more rapidly from distended coils, and they are the ones most frequently injured. A longitudinal wound gapes more widely than a transverse, the edges being sepa- rated by the strong circular muscular fibers. A small penetrating wound may be plugged by everted mucous membrane. A wound in the mesenteric border is most difficult to repair. A gunshot wound in the lower left quarter of the abdomen will certainly inflict multiple intestinal injuries. As a rule, however, they will be found in a comparatively short loop of intestine, with a few scattered in distant coils. Large Intestine (intestinum crassum). — Of this there are the following divisions: cecum, ascending, transverse, and descending colon, sigmoid flexure, and rectum. It is distinguished from the small intestine by its larger size, by its more fixed position, and by the appen- dices epiploic®. Furthermore, the longitudinal muscu- lar fibers which are spread in an even layer over the small intestine are gathered into three well-marked bundles on the surface of the colon. These are about one-half the length of the remaining colon layers, and so throw it into sacculations separated by transverse constrictions, which project into the lumen of the bowel as plicae or valvulae sigmoidse. The length of the large intestine is five or six feet; its capacity is about one gallon. The cecum — that part of the large intestine below the ileocolic opening — is situated in the right iliac fossa, upon the iliopsoas muscle. Anteriorly, it is in contact with the anterior abdominal wall above the outer half of Poupart's ligament, except when the omentum is interposed. Its exact position depends upon its peritoneal relations. As a rule, it is completely invested by peritoneum, though it has no mesocecum. In a small percentage of cases the upper part of the pos- terior surface is not covered by peritoneum, and so comes in contact with the areolar tissue of the posterior abdominal wall. It may be long and movable, its free extremity hanging into the pelvis or projecting across the mid-line to the opposite side of the body. Or it may be situated at any point between the iliac fossa and a position immediately beneath the liver, this bcint; its location in the embryo of three months. The latter variation occurs in consequence of an arrest of its nor- mal descent into the false pelvis. When the posterior wall of the cecum is not entirely covered by peritoneum, an infection readily travels from it to the areolar tissue about the right kidney. The appendix vermiform is (processus vermiformis) originally arose from the apex of the cecum, but, as the right half of the hitler exceeds the left in development, tin- iiluli appendix arises from its inner and posterior surface a little below the ileocolic opening. Its average length is between three and four inches, but it may vary 18 from one to nine. Its cavity, lined by mucous membrane continuous with that of the cecum, tends to undergo obliteration with advancing age. The lumen is narrow- est at the orifice, which is guarded by a valve of mucous membrane. It is enveloped by peritoneum throughout, and is provided with a triangular mesentery derived from that of the small intestines. The mesentery is rarely complete, allowing the end to hang free. Within the mesentery is a branch of the ileocolic artery, fur- nishing its blood supply. The exact position of the appendix is variable, but it will always be found by following one of the longitudinal bands of muscular fibers seen on the surface of the colon. Two main posi- tions are observed. In one, the appendix is truly an intraperitoneal organ hanging free from the cecum. It may be directed inward and upward, or downward; it may be curled on the brim of the pelvis or may hang into the pelvic cavity; or it may occupy one of the fossae about the cecum. In the second position the appendix is practically an extraperitoneal organ, lying between the posterior surface of the cecum and the colon. The base of the appendix, as indicated by McBurney's point, lies two inches from the spine of the ilium on a line drawn from the spine to the umbilicus. Colon. — The ascending colon (colon ascendens) reaches from the cecum to the under surface of the liver, passing through the right lumbar region into the hypochondrium. Here it turns to the left forming the hepatic flexure (flexura coli dextra) and becomes the transverse colon (colon transversum). As a rule, it has no mesentery, being held in position by the peritoneum which covers its anterior surface and sides. Behind, it is separated by loose areolar tissue from the quadratus lumborum and transversalis muscles and the lower and inner part of the right kidney. In front it is in contact with the anterior abdominal wall, omentum, and a few coils of the small intestines. The relation to the ante- rior surface of the kidney is most important. An ab- scess of the kidney or a perinephritic abscess may open into it without involving the peritoneum. A kidney enlarged from infection or a tumor carries the colon forward on its anterior surface. This may be deter- mined by inflation of the colon. The transverse colon suspended by a mesocolon is deeply placed at its ends, but comes in close contact with the anterior abdominal wall in the remainder of its course. As a rule, it lies along the subcostal line, but may descend as far as the pelvis. Above, it is first close to the fundus of the gall bladder; adhesions between the two are common, and calculi may ulcerate into it from this viscus. The greater curvature of the stomach and the lower end of the spleen lie above in the remainder of its course. The descending colon (colon descendens) begins at the splenic flexure (flexura coli sinistra), at which point it is situated deeply in the left hypochondrium. From here it descends through the left lumbar region along the outer border of the kidney. Its peritoneal relations resemble those of the ascending colon. A relation worthy of not ice is that to the kidney. The left kidney lies more internal to the descending colon than the right does to the ascending colon. Anteriorly, the descending colon is more constantly covered by omen- tum and small intestine than is the ascending. Fecal matter may accumulate in the colon in any part to such an extent as to simulate a true tumor; consequently colonic flushing is always a wise procedure in the examination of an intraabdominal growth. The sigmoid flexure (colon sigmoideum), continuing the descending colon, extends from the iliac crest to the third sacral vertebra, at which point it becomes the rec- tum (intestinum rectum). It is provided with a mes- entery attached transversely in front of the psoas muscle. Its length and position are variable. It may form a per- fect loop occupying the pelvis, or, when the bladder and rectum are distended, lying near the umbilicus. At times it tests in the left iliac fossa. It is this loop which sur- geons open in a left inguinal colostomy. In the descend- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Orcans, Regional Anatomy ing colon, the opening may be through the posterior ab- dominal wall without exposing the peritoneal cavity, but as the position of the artificial anus is an awkward one for the patient the operation has been abandoned. The remaining portion of the large intestine is the rectum, situated within the true pelvis, with which it is usually described. The spleen (lien) is situated obliquely behind the stomach in the epigastric and left hypochondriac regions. It lies beneath the eighth, ninth, tenth, and eleventh ribs; its long axis, measuring five or six inches, corre- sponds in direction with the tenth rib. It is separated fn mi these ribs above by the lower border of the lung and pleura, and throughout by the peritoneum and diaphragm. A normal spleen cannot be palpated. The enlarged spleen appears beneath the costal arch at the level of the tenth and eleventh ribs. It may be distinguished by the notches, one or two, in it< anterior border and by its respiratory movement. Unlike the movement of the liver, which is vertical, the movement of the spleen is oblique, that is, toward the umbilicus. The dulness of the spleen as outlined by percussion is an oval area extending from the ninth to the eleventh rib in the posterior axillary line. Four surfaces are described on the organ, each indicating a relation to a neighboring viscus. The phrenic surface is in contact with the diaphragm. The renal surface, directed downward and inward, is in contact with the left kidney. The gastric surface faces forward and in- ward and is iii contact with the posterior surface of the stomach; on this surface is the hilum. Finally, the lower blunt end is the basal surface upon the splenic flexure of the colon and the tail of the pancreas. The peritoneal relations of the spleen are extensive. With the exception of the small region corresponding to the hilum it is covered by the visceral peritoneum of the greater sac. The blood-vessels and nerves reach the organ between the layers of the gastrosplenic omentum. Wounds of the spleen are accompanied by severe hemorrhage. When it is extreme it may become necessary to remove the organ for this reason. The pancreas, situated behind the stomach, in front of the first and second lumbar vertebrae, reaches from the concavity of the duodenum on the right to the spleen on the left. On the surface of the abdomen its position is from two and one-half to five inches above the umbilicus. To expose the pancreas the lesser peritoneal cavity must be opened. It is then seen lying behind the posterior layer of this cavity. It can be palpated only when pathologically enlarged, as by a carcinoma or cyst. The organ -does not move with respiration. The anterior surface of the pancreas is in contact with the posterior surface of the stomach, while the posterior surface lies in front of the aorta, the superior mesenteric artery, the splenic vein, and the left kidney with its vessels. The head is encircled by the duo- denum. The pancreatic duct crosses the gland from left to right, and is buried in its substance close to the posterior surface. Its course is straight until it reaches the head, at which point it turns obliquely downward to enter the second portion of the duodenum, close to or in common with the bile duct. Retention cysts of the duct or of some of its smaller branches occur, and may attain a large size. In general appearance such a cyst resembles a solid or a. cystic tumor of the kidney, the differential diagnosis being at times impossible. Kidneys (renes) . — For the greater part the kidneys are situated deeply in the hypochondriac regions, their lower ends, however, extending into the adjacent lumbar and umbilical regions. In consequence of the position of the liver on the right side, the right kidney is somewhat lower than the left. As regards the vertebral column, the kidneys are opposite the twelfth dorsal, the first and second, and sometimes the third lumbar vertebra?. The upper end of the right kidney reaches a line drawn transversely outward from the tip of the spine of the eleventh dorsal vertebra. Its lower border reaches a similar line drawn from the lower edge of the spine of the second lumbar vertebra. This line is usually about an inch and a half above the iliac crest. Its upper end is nearer the spinal column than the lower. The pelvis of the organ is opposite the transverse process of the second lumbar vertebra. A'i laiimix. -The posterior surfaces are similar, but the anterior surfaces differ on the two sides. Posteriorly, the kidneys are not covered by peritoneum, being con- nected by areolar tissue with the diaphragm, the anterior layer of the lumbar aponeurosis covering the quadratus lumborum, and, more internally, the psoas magnus muscles. Above, the relation to the dia- phragm is important, as this structure separates the kidney from the twelfth rib, and sometimes, on the hit side, from the eleventh. An inspection of Plate 1 will show that the pleura descends over the inner ends of these ribs, and so lies between the upper ends of the kidneys and the surface of the body. Notice especially that the pleura does not descend below the angle formed by the lower border of the twelfth rib and the outer edge of the quadratus lumborum muscle. However, the development of the twelfth rib is not constant, it being incompletely developed or entirely absent in many cases. The individual cases can be recognized only by counting the ribs. On the other hand, the lower limit of the pleura and its relation to the kidney are constant, and in a case of anomalous twelfth rib the pleura will lie unprotected by rib in this locality. The importance of this condition will be appreciated later. Anteriorly, the right kidney has the following rela- tions: At the extreme upper end is a small non-peri- toneal surface in contact with the suprarenal capsule, below and external to which is a large peritoneal surface in contact with the liver. The area about the hilum is non-peritoneal and is in contact with the descending portion of the duodenum. Below this region and internal to the liver area are two regions: an outer non- • peritoneal covered by the colon, and an inner peritoneal covered by coils of small intestine. The anterior surface of the left kidney is crossed just above its center by the pancreas, no peritoneum inter- vening. Above the pancreatic surface three organs are in relation with the kidney: the suprarenal capsule, the stomach, and the spleen — the first being the only organ not separated by peritoneum. Below the pancreas the surface is largely covered by peritoneum and small in- testine, the exception being the outer border, which lies behind the colon. From the description of the situation and relations of the kidney a number of practical points are evident. As a general rule, it is safe to say that a palpable kidney is enlarged or dis- placed. Only in very favorable subjects, especially thin women, in whom the organ is frequently lower than normal, can we certainly feel the normal kidney, and then only the lower third, as the upper two-thirds lie behind the lower ribs. Bimanual palpation should be used, the hand placed in the loin being depended upon to lift the kidney against its fellow which presses upon the abdomen. In this connection note the posi- tion of the colon; it is nearly over the center of the right kidney, but to the left of or outside the left kidney. The kidney has no respiratory movement. It is recognized by its characteristic shape, and by the large artery which enters the hilum. The kidney may be reached through the loin or by way of the perit- oneal cavity. In the former method various incisions are employed. The most important landmarks are the outer edge of the quadratus lumborum muscle and the twelfth rib. In all incisions it should be remem- bered that the pleural cavity is near, and it should be avoided. As indicated above, when the twelfth rib is of normal development, an incision may be carried closely into the angle between this muscle and the ribs. When the rib is short or absent, which is to be determined only by careful examination, then the location of the normal rib should be borne in mind, 19 Abdominal Organs, Regional Anatomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES and the incision should be carried no farther than the normal angle. The attachment of the quadratus to the eleventh rib in these cases should not mislead one. The ureters occupy a position in the hilum pos- terior to the artery and vein. Their average length is seventeen inches. Beginning as a well-marked dilatation, called the pelvis of the kidney, the ureter passes downward on the psoas magnus as far as the brim of the true pelvis, which it enters by crossing either the common or the external iliac artery. It is accompanied by the spermatic vessels in the male, and by the ovarian in the female. This portion of the ureter may be reached through the postperitoneal space. In searching for it the operator must raise the parietal layer of the peritoneum, to which structure it will be found adherent. The peritoneum is a closed serous sac with the excep- tion of the tubal openings in the female. It appears as though placed within the abdominal cavity in front of the viscera, the anterior or parietal layer of the sac lining the posterior surface of the anterolateral wall, while the posterior or visceral layer is tucked about the viscera, enclosing them more or less completely, and attaching them to the abdominal walls. The exact relations of the membrane to the individual viscera have been noted in the descriptions of the latter , and are of importance in the spread of disease from viscera to peritoneum. Many injuries and diseases of the abdom- inal viscera are dangerous only as they involve the peritoneum. It is a well-known fact that an infection approaching the membrane from its outer surface is of _ . , , D ■. Outline of Diaphragm Parietal Peritoneum , 6 Gastro-hepatic Omentum Transverse Meso-colon Great Omentum Parietal Peritoneu Vesicula Seminalis Fin. 11. — Diagram of the Peritoneum in the Adult Male (vertical .section). S, stomach; P, pancreas; D, duodenum: H, urinary bladder; A', rectum; Tt\ transverse colon; .S7, small intestine; the arrow is through the foramen of Winslow. (Buchanan.) much less danger lhan one approaching from the inner. The former is soon localized and results in the formation tit an abscess; absorption of toxins is slight. When the inner surface is infected, the tendency of the disease is to spread rapidly, and the absorption of septic toxins is intense. These phenomena are explained by the microscopical structure of the peritoneum. It consists e entially of two layers. The outer layer is composed of fibrous ami elastic tissue. It supports the inner layer, which is composed of flat endothelial cells. Between the margins of the cells are numerous openings of lymphatic vessels, stomata, which are the active absorbents of the peritoneum. Some regions, as those of the diaphragm and small intestines, are especially rich in lymphatic vessels, while in others, as the omentum, the number is small. For this reason a peritonitis is more dangerous in certain localities than in others. When the anterolateral abdominal wall is opened, the peritoneal cavity is also opened. In the living body, however, no cavity exists, parietal and visceral layers being held in contact by muscular action and Visceral Pentone ■hepaiic Omentum Hepatic Aitery Vena Porta: ^\< SV\ Common Bile-duct Fir,. 12.- -Diagram of the Peritoneum at the head of the Foramen of Winslow (transverse section;. tBuchauan ) atmospheric pressure. The great omentum is seen hanging from the greater curvature of the stomach, covering more or less completely the viscera in the lower half of the cavity. Normally it should do so quite completely, but it may be found collected in a roll about some organ or loop of intestine. This is especially the case when there has been a former peritonitis. The omentum serves to protect the in- testines, and also as a storehouse for fat, but its most important function is that of limiting an infection. It readily contracts adhesions about organs, such as an inflamed appendix or a perforated intestinal coil, and so prevents infection of the general peritoneal cavity. In extensive pelvic suppuration, the omentum may completely exclude the pelvic from the general abdom- inal cavity. Behind the omentum are the small intestines, and, on either side of the posterior wall, the ascending and descending colon. The mesentery of the transverse colon is raised with the great omentum. As it is attached transversely across the posterior abdominal wall, it divides the cavity into two compartments. The upper contains the liver, stomach, and spleen. It also includes the lesser peritoneal cavity. The lower compartment con- tains the small intestines and the colon. It is sub- divided by the mesentery into an upper right and a lower left portion. The upper portion ends below in the right iliac fossa. Consequently a fluid effused in this region or on the upper surface of the mesentery will gravitate into the right iliac region. The left and lower portion passes to the pelvis, into which cavity fluid will descend when it originates below and to the left of the mesentery. The relations of the lesser peritoneal cavity are de- scribed with those of the stomach. Thomas A. Olney. Abdominal Section. — The large number of abdom- inal operations permit of a selection of the incision best suited for the purpose. A good incision must possess the following requisites. 1. It must give the best possible access to the region to be operated on. 2. It must injure least other organs. 3. It must promise the strongest possible scar for the prevention of hernia. 3) REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \inii.iiiiii.ii Section 4. In woman, at least, the cosmetic effect of the scar is to be considered to a certain extent. There are other desiderata to be fulfilled. For instance, in certain operations, like appendicitis, gall-bladder operations, and so on, one may wish to make a smaller incision which will suffice only if the case does not prove too difficult. If difficulties arise, and a larger incision is needed, the selected incision must permit of this enlargement to obtain free access without sacrificing any of the tissues so far saved. The incision must also permit of subsequent drainage, if necessary, in any of its parts, without too much probability of the formation of a hernia. There are certain abdominal affections in which there is no choice as regards the situation, at least, of the incision, as, for instance, in the case of solid immov- able tumors, abscesses, hernias, fistulas, and so on. Then only the direction of the incision will have to be considered. For all other operations there was a time when laparotomy as such meant the median incision, be- cause that gives access to practically every region of the abdomen, inflicts practically no injury on the tissues, and is attended with the least possible hemorrhage. The conditio sine qua non for a sound scar, to prevent hernia, is primary union; but it has been found that even where such was the case, quite a large percentage (some statistics claim as many as ten per cent.) of hernias resulted from a median inci- sion. This is especially true in cases of older women, who have borne children, with a resulting diastasis of the rectus muscles. The reason for this is appar- ent. The median incision severs practically only one layer of tissue, that is, the aponeurosis, which is poorly nourished by vessels, like all tendinous tissues of the body. And thus its very simplicity is its disadvantage; namely, that the whole abdominal wall at this part of the body consists of only one layer. In any other part of the abdomen the operator has to go through several layers which, as modern surgery has taught us, are to be united by separate sutures in layers. For this reason, chiefly in all abdominal gyneco- logical operations, the median incision has been aban- doned entirely by a great many of the best operators. Special incisions have been advised for a number of typical operations, as diseases of the appendix, gall bladder, stomach, spleen, and so on. So that the median incision, either above or below the navel, is employed practically only in so-called exploratory operations, where either the nature of the disease cannot be diagnosed with sufficient certainty before the operation, or where its exact location cannot be ascertained, as in ileus, volvulus, and like conditions. The preparation of the patient for abdominal sec- tion has become extremely simple. I will omit, of course, all special preparations which may be neces- sitated by the nature of the disease for which the patient is to be operated on, and will mention only those preparations that are essential for abdominal section as such. The preparation of the operative field is now done almost entirely by simply painting the skin of the abdomen (after the same has been shaved) with a ten per cent, tincture of iodine. Care should be taken that the skin is absolutely dry when the tinc- ture is applied. This is achieved by rubbing the skin either with ether or with iodine benzine. A great many operators apply this one and only coat of iodine immediately before the operation, when the patient is on the operating table, without any other preparation at all, while others first have the patient bathe, after which the skin is well dried, and then the evening before the operation a good coat of iodine is applied; this is repeated the next day on the operat- ing table. It has been found, however, that the one single application of iodine is sufficient. Care has to be taken not to bring the peritoneal covering of internal organs, especially intestines, into contact with the iodinized skin as this is liable lo produce adhesions. If intestines or other organs have to be brought out of the abdominal cavity and laid for a while on the abdominal wall, the skin should be covered u it h ei! her rubber I issue or gauze pads which are attached with Mikulicz, or Michel clamps to I lie peril oneal edge. The simple preparation of the skin of the field of operation being i lpleted, I lie patient is either left in the horizontal position on tin- table or put into Trendelenburg's <>r any other position, according to the nature of t he operation. A Her I he en I ire patient, with the except ion of the immediate field of opera! ion. has been covered in the usual v. ay by sterile sheets and towels, thi' actual incision is made by the operator. I ii-t the skin and the underlying tissue are severed down to the aponeurosis in one or several strokes according to the thickness of fat. The further details of the incision vary in accordance with the type of incision selected, and will be described presently. The last step, incision of the peritoneum, is again alike in all types of incisions; it should be made by catching the peritoneum and lifting it up by two surgical forceps or clamps, between which the incision is made. Thus any injury of the underlying intes- tines is avoided. The free edges are at once caught by Mikulicz clamps, which are applied on each side as the incision in the peritoneum is enlarged with scissors over the introduced finger as a guide, or over one of the peritoneal spoons. After this retractors are introduced and the exposed viscera covered by an abdominal pad of large flat layers of gauze, hemmed together. To avoid losing any of these pads in the abdominal cavity, many surgeons have a tape (about twelve inches long), sewed into one of the corners of the pad ; the free end of the tape is grasped by a clamp which remains outside the wound. I shall now describe the different methods of inci- sions for different operations. Probatory or Exploratory Laparotomy. — Incisions 4 and 6 of Plate II, Fig. 1 show the median incision, either epigastric or hypogastric. Either can be lengthened, if necessary. In the latter case the navel is to be passed around on the left side, or even excised, as some operators prefer. Appendicitis Operation. — Two incisions are chiefly known and practised in this country — the McBurney and what is commonly known as the Kammerer incision. The former is seen in Plate II., Fig. 2, incision 5, the latter in Fig. 1, incision 5. The Mc- Burney incision is doubtless, physiologically, abso- lutely proper. It is, technically, not very easy, and gives exceedingly little room after it has been com- pleted. While it suffices in simple interval eases, it is absolutely impracticable even when only adhesions are found, and especially if other difficulties arise, like the retrocecal situation of the appendix, very dense adhesions, or unsuspected encapsulated old abscesses. To gain enough room, then, one has either to destroy the carefully prepared gridiron by incisions across the fibers of the muscles, or one has to follow the advice of Sprengel, and cut across the anterior sheath of the rectus, retract the rectus muscle with the epigastric vessels toward the median line, and then incise the peritoneum, plus transverse fascia. There is no trouble in uniting such an incision, and drainage in any of the corners of the wound can easily be carried out if necessary. In the other incision, known as Kammerer's, the anterior sheath of the rectus is divided, and the muscle itself, together with the vessels, drawn toward the median line. Before incising the posterior sheath with the attached peritoneum, the nerve branch which appears in the wound, is also drawn aside in the median direction by a blunt hook. In order to do this, one usually has to liberate the nerve by scratch- ing along its edge with a sharp-pointed knife. This 21 Abdominal Section REFERENCE HANDBOOK OF THE MEDICAL SCIENCES incision gives good access. If difficulties arise, the incision can easily be lengthened to any desired degree. Its closure — of course in layers — is easy; it permits drainage in either angle of the wound. In the very latest literature a great deal of objection has been raised against this incision on account of its not being physiological, and also by reason of the fact that it necessitates severing the nerves supplying the different parts of the rectus muscle. In those cases where the nerve or nerves, according to the length of the incision, had been severed, paralysis of that part of the rectus muscle has been observed, with a hernia as a result. But this can happen only when, on ac- count of unusual difficulties arising during the opera- tion, the incision has to be lengthened unduly. Other. \\ ise, the results of this incision are very good indeed- Fig. 13. — Lines of Abdominal Incisions. 1, Sprengel's gas- trotomy incision; the same, when on the right side, is Bakes's gall-bladder incision. 2, Sprengel's incision for major operations on the stomach, also for operations on the transverse colon. 3, For operations on the spleen. 4, Bakes's incision for liver operations. 5, Bakes's new plastic kidney incision. 6, Rep- resents Mackenrodt's incision of the sigmoid flexure and trans- peritoneal operations on the rectum. 7, Resection of the cecum. 8, Pfannenstiel's incison for gynecological abdominal operations. (Figure after Bakes.) Operations on Gall Bladder and Duels. — For these operations we need very free access to the seat of the disease, especially in fat patients, in whom the wound becomes exceedingly deep. At the same time, the structure of the abdominal wall should, according to modern ideas, be preserved as much as possible. To achieve this a number of incisions have beeD advised. The simplest is Kocher's, shown in Plate II., Fig. 2 as incision 1, and he claims that in his large ex- perience he has always had verj' good results from this incision. Incision 1 in Fig. 1 shows Robson's modifi- cation of Arthur Deane Bevan's. It is very good. Incision 2, Fig. 1, shows Kehr's bayonet incision, as he used to make it — an excellent incision. Following the clamor for more physiological inci- sions, Kehr has now devised an incision, which is shown as No. 2 in Fig. 2. He claims all the advantages for this incision, with the least possible injury in an anatomical sense. 22 In a rather heated controversy, whose fervor it is not very easy for outsiders to understand, Sprengel, of Braunschweig, recommends his incision, No. 8, Fig. 2. • Both are about equally good. Bakes recom- mends for simple gall-bladder cases, an incision on the right side, similar to the one on the left side, shown as No. 1 in Fig. 13. For more difficult operations on the liver, he recommends incision 4, Fig. 13. The principal difficulty offered by any incisions carried across the rectus muscle consists in uniting the re- tracted fibers of the muscle by suture. If the fascia and peritoneum are sewed in a layer, and then the two angles of the wound elevated by single hooks or inserted threads, the suture of the retracted fibers of the muscle is somewhat protracted, but not too diffi- cult, and is in all cases absolutely secure. Especially is there less difficulty in fighting the protruding intestines, as so frequently happens in lengthy in- cisions. Operations on the Stomach. — Formerly, the median epigastric incision was nearly universal; then a para- rectal incision was adopted, shown as No. 3 in Plate II., Fig. 2. Very lately Bakes and Sprengel recommend incisions as shown in Fig. 13, Nos. 1 and 2; No. 1 for simple gastrostomies and No. 2 for the more difficult operations on the stomach. A very agreeable feature of the cross incision is that the patients complain of less suffering from retching, vomiting, and coughing after operations. Operations on the Pancreas. — Since the diagnosis of diseases of the pancreas, acute or chronic, has become more certain or, at least, more probable, median incisions as formerly used, or as employed for ex- ploratory incisions, will be gradually abandoned and cross-sections will be preferred. An incision like No. 2 in Fig. 13, will be extremely well adapted to such a purpose. Laparotomy for Operations on the Female Organs. — Pfannenstiel's incision, No. 8 in Fig. 13, has become the incision par excellence for gynecological abdominal operations. It not only is important for its cosmetic effect, but it prevents, with practically absolute certainty, the formation of postoperative hernia. The incision through the skin is made as indicated in the drawing, and the fascia is also incised crosswise. In the middle line the fascia has to be dissected with scissors, while the rest of the fascia can be split and drawn aside without cutting. After that the recti muscles are divided in the middle line and the perito- neum is then opened. No nerves whatsoever are severed by this incision, therefore atrophy of the recti muscles is impossible. It has been claimed that the Pfannenstiel incision does not give enough room for difficult operations on the uterus and its adnexa; therefore a number of authors have used instead of a cross incision into the fascia, a curved incision with the concavity upward. This fascia incision can be carried as far to both sides as may appear necessary. No necrosis of fascia in aseptic cases has ever been observed. As in all incisions that follow physiological rules, the adaptation of the severed tissues is so much better that the patients can be permitted to get up much sooner than formerly. No abdominal binder is necessary after the Pfannenstiel incision. For extremely difficult operations in the small pelvis, Bardenheuer's incision may be used, as seen in No. S of Plate II., Fig. 1. The incision severs skin and fascia in the same direction, and the recti are cut off shortly above their insertion on the symphysis. I have omitted any discussion of operations on the bladder, kidneys, and ureters, as these organs are extraperitoneal. I will mention only the new plastic kidney incision of Bakes, as seen in No. 5 of Fig. 13. For operations on the spleen a V-shaped incision, on the left side, as shown, on the right side, in No. 8 of Plate II., Fig. 2, may be applied with advantage; or incision No. 3 in Fig. 13. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES PLATE II • J II - i a- 2 * i ? = : M: | i J: '" S - \z - ~ » a .2 j '- s-S: / _^ -- .a . ** •£ a~ s 3 S S'S - r = . i 43 - - - a S'Soe 2 C O C *■ ' . 3 a \ •- - X ~ * 2 SV E - •;": = — :: ^ - r _ . . . ~ r. ■r. ~ — = J B.S h -=_■£ — - c = - t^. 0) o -a ~ t c - - n = — .. a - - C c a - ... s ^f OS c - - > a >. r pq 09 a CO = en - n a / 3 — T c E < « a , ^ a : i _^ a REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Tumors, Diagnosis For inguinal hernia or the Alexander operation, incision No. 7 of Plate II., Fig. 1, is proper. Operations on the Intestines. — Incision No. C, Fig. 13, represents Mackenrodt's incisionfor operations on the sigmoid flexure and transperitoneal operations on the rectum. Resection of the cecum is well accomplished by using an incision like No. 7 in Fig. 13. For operations on the transverse colon, incision No. 2 in Fig. 13 is indicated. For operations on the splenic flexure of the colon, Kocher advises an incision like No. 3 in Plate II., Fig. 1, while No. 7 in Fig. '_' is for inguinal colostomy. An incision for a large umbilical hernia, according to Mayo's method, is shown in No. -1, Plate II., Fig. _'. I have mentioned previously that the principal requisites for success in performing these operations, so far as abdominal section itself is concerned, are: absolute asepsis, complete hemostasis, and the most exact suture, with the avoidance of dead spaci Wherever drainage is necessary, either because the hemostasis cannot be as exact as desired, or by reason of the presence of pus, the entire abdominal section should be closed with the exception of a small part in one of the corners, where a cigarette or other drain may be inserted. For suture material most operators now use plain catgut for the peritoneum, chromicized catgut in interrupted sutures for the fascia and muscles, and silkworm sutures or Michel's clamps for the skin; the latter can be applied only where the skin is not too thick. For dressing the wound most operators now use adhe- sive plaster strips to hold the dressing in place, and at the same time compress the wound, also to relieve some of the strain on the wound produced by vomiting, retching, coughing, and so on. Over this a binder is applied which is made to conform to the contours of the body by the application of safety-pins where necessary. Thigh-straps may be combined with the same. Some operators place a sand-bag over the operated region to prevent the accumulation of blood in possible dead spaces. Otto Kiliani. Abdominal Tumors, Diagnosis of. — The word tumor is used here not in the restricted sense of a neo- plasm but in the etymological sense of a swelling. It is at once evident from this that a large number of pathological processes affecting all the organs con- tained in the abdomen and the tissues making up the abdominal walls must be considered. This was deemed necessary because we start with the assump- tion that in a certain given case a tumor has been found in the abdomen and it is necessary to discover what and where it is. All details of etiology, path- ology, and symptomatology have been omitted except in so far as they have a direct bearing upon the dif- ferential diagnosis. For such details reference must be made to more special articles. Furthermore, the diagnosis of conditions which ultimately lead to the formation of demonstrable tumors has been omitted, and the discussion of such conditions will be limited to their course after the formation of a tumor. For example, when speaking of cancer of the stomach it will be assumed that a tumor has been discovered. When confronted with an abdominal tumor, it must be remembered that the diagnosis should go beyond the mere recognition of the existence of a tumor in the abdomen. We must determine first the organ or tissue in which the tumor is located, and second the nature of the tumor. If the tumor is believed to be a malignant neoplasm, we must decide if possible, whether the tumor arose in the organ in which it is discovered or is merely a tumor secondary to a primary tumor in some organ yet to be deter- mined. If the tumor found is believed to be primary, secondary deposits in other organs must be sought. In other cases we must hunt for the cause of the tumor. If, for example, a certain tumor is thought to be a gal] bladder distended with fluid, effort Bhould be made to ascertain the character of the fluid and the cause and site of the obstruction which prevents the escape of the fluid from the gall-bladder. With so broail a subject it is evident that only the more important methods, facts, and pathological condi- tions can be included. After a brief discussion of the methods of examina- tion employed, we will consider what miiilit be called tumors of the abdomen as a whole, such as ascites, diffuse peritonitis, lipomatosis. Then the various organs will be grouped according to their relations to the colon, and each group considered in turn. The organs situated to the cephalic side of the trans- verse colon, the liver and gall-bladder, the stomach, pancreas, and spleen, will be described first; then will follow the organs behind the colon, the kidney, adrenal bodies, and perirenal tissue; next will come the organs within the arch of the colon, the small intestines, mesentery and omentum, peritoneum, lymph glands, aorta, uterus, ovaries, bladder, spinal column, and lastly the colon, appendix, and walls of the abdomen. With each organ we shall so far as possible take up first the circulatory disturbances, then the inflammatory processes, cysts, neoplasms, and malpositions. It is not necessary to state that this order cannot be followed absolutely, but it can be approximately, and will be found greatly to fa- cilitate a grasp of this subject, probably the most diffi- cult matter handled by the diagnostician. Methods of Examination employed include the physical, chemical, and microscopical: the first hav- ing in general an especial bearing upon the localiza- tion of the tumor, while the second and third are of more value in determining the nature of the tumor. Physical Methods. — Inspection. — The patient should be placed on a firm narrow bed or table in such a way that the source of the light lies in a line with the median line of the body, either directly above or at the head or foot of the patient. The purpose of this is to avoid any uneven distribution of the shad- ows. The kind of light employed is usually a matter of indifference, but in eases in which there is reason to suspect the possibility of a jaundice the patient must be examined by daylight, for the well-known reason that no artificial light shows even the deepest shades of jaundice. Take note first of the size of the abdomen, especially of any disproportion between the size of the abdomen and that of the other portions of the body. Next, note the shape of the abdomen. Is the abdomen symmetrical? Are there any portions more prom- inent than the corresponding ones of the other side, or is the upper half out of proportion to the lower half? If any part appears large, does it appear sharply outlined or does it merge gradually into the surrounding parts? Does the surface of the enlarge- ment appear smooth or nodular, and are the outlines rounded or irregular? Does the mass move; and if so, does it move with the respiration, the pulse, or independently of either? Almost any tumor of the abdomen may show respiratory or pulsatile move- ments (the exceptions will be stated later), but only a few show independent movements. These are tumors from the stomach, intestines, and uterus. Visible vermicular movements of the stomach and intestines are commonly seen in patients with thin abdominal walls and are not in themselves patholog- ical. It is only when they are usually intense and continuous and in combination with distinctly path- ological symptoms that they need attention. The word vermicular quite accurately describes the motion, for it looks exactly as if some large worm were moving under the skin. The site and direction of the movement should be noted. In general the pcris- talic movements of the stomach are limited to the upper and median portion of the abdomen and pass 23 Abdominal Tumors, Diagnosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES from left to right. Peristaltic movements of the stomach from right to left are pathological. The movements of the small intestines are central and irregular in direction. Those of the large intes- tine correspond to the relatively fixed position of the colon and vary in direction with the portion of the colon affected. The peristaltic movements above the site of any stricture in the gastrointes- tinal tract, either acute or chronic, are more active than normal, and therefore persistently exaggerated movements point to some obstruction, but do not in t hem-elves prove such obstruction. The independent movements of the uterus are of two sorts: fetal and uterine. The presence of the fetal movements is at times a most important point in the differentiation of abdominal tumors. The move- ment- arc altogether irregular in time and intensity, and may be simulated by the peristalsis of the small intestines. The expulsive contractions of the uterus are not often visible, but may be so. Inspection of the abdomen includes attention also to any subcutaneous collateral circulation, either arterial or venous. Such circulation often gives the clew to the site of the Obstruction, which neces- sitates a collateral circulation and may give some idea of the degree of the obstruction. Note also any localized edema or inflammatory process. Often much valuable information may be gained by changing the amount of gas in the stomach and intestines. Not only do we gain information as to the exact location and size of these organs, but we learn much of their relation to the tumor found. Various methods have been employed for this pur- pose, but the following require only such apparatus as should be in the armamentarium of every physi- cian. The stomach may be inflated by means of a Seidlitz powder mixed after drinking instead of be- fore, or one can use saleratus in solution followed by a little vinegar. This method is not entirely without danger, because the pressure resulting from the gas envolved cannot be accurately estimated. Acci- dents, however, are rare. Another method consists in the passage of the stomach tube and inflation of the viscus by means of a pump. This has the advan- tage of enabling one to use as much or as little gas as desired, and permits the immediate removal of the gas if necessary. The colon is inflated by passing the rectal tube well up into the descending colon and forcing in air by means of a pump, the ordinary bicycle pump being perfectly adapted to the purpose. A rather large, cone- shaped rectal tip is better than the rectal tube, for it prevents the escape of the air, but is not so easily supplied as the tube. As the air passes upward and distends the colon we are able to learn the exact course of the colon and its relations to the tumor. Harris, of Chicago, has drawn especial attention to the value of the relation of the colon to abdominal tu- mors in the differential diagnosis of such tumors. He substitutes for the old and superficial division of the ab- domen into nine areas — the right and left hypochon- driac, lumbar, and inguinal regions, the epigastric, umbilical, and hypogastric regions — an anatomical division into fourareas. The borders of these areas are not fixed by external points, but are located by the inner or mesial layer of the longitudinal colon and the inferior or caudal layer of the transverse colon. The resulting areas are a central area, surrounded by meso- colon; aright and left posterolateral area, lying external to and behind the mesocolon; and a superior area, lying above the transverse mesocolon. While the boun- daries of these areas are not fixed, their position is easily ascertained by determining the position of the colon by air distention. In the central area, surrounded by the distended colon, are found tumors of the omentum and mesen- tery, retroperitoneal tumors, localized peritoneal exudates, tumors of the small intestines, tumors of displaced and movable kidneys, and all tumors of the female generative organs rising into the abdomen. In the superior region we find tumors of the liver, gall bladder, stomach, lesser omentum, pancreas, retroperitoneal lymph glands, and aneurysms of the celiac axis. Tumors of the spleen pass forward close to the anterior wall, in front of the splenic flexure of the colon and the neighboring parts of the transverse and descending colon. Tumors of the kidneys, suprarenal bodies, and the connective tissue bordering on these organs, tumors from remains of the Wolffian bodies, carry the colon inward and forward. But tumors from floating kidneys may appear in the central area, i.e. sur- rounded by the colon. Skiagraphy. — To these methods of inspection there has in recent years been an important addition, namely, the inspection of bismuth suspensions by means of the z-ray. While this method is of but little value in the great majority of the cases of abdominal tumors, in some it is of almost major im- portance. A suspension of bismuth salts is given by mouth or per rectum or both and inspection made at once by means of the fluorescent screen. Plates should also be made at varying intervals over a period of twenty-four hours. When the bismuth is given by mouth the intervals between the plates should be short, at first only minutes long, but after the first hour, the intervals should be gradually lengthened. In this way accurate information as to the size. location, and motility of the stomach maybe obtained and in some cases, the presence and size of a carcin- oma can be accurately proven. The colonic injections enable one to ascertain, the location of the colon and the presence of kinks, strictures, and dilatations. Work of this sort requires first, a good x-ray operator and second, considerable experience in the interpre- tation of the results obtained. Palpation. — This method of examination is of much more general application than inspection, for many tumors easily palpable are not visible. Pal- pation should always be preceded by thorough and certain evacuation of the bowels, otherwise fecal masses may lead to errors. The patient should be examined first in the dorsal position, but in some cases a lateral, a knee-chest, or an erect position will yield results not otherwise obtainable. The patient should relax the abdominal muscles as completely as possible. This is often easier when the thighs are flexed on the abdomen and the mouth held open. In difficult cases better relaxation is obtained if the patient is placed in a bath of warm water and exam- ined in the bath. In still more difficult cases general anesthesia must be employed. Palpation should be made gently but firmly, and any pressure used should be applied gradually; counter-piessure from behind is often a help. Sometimes, and this is especially true when there is considerable fluid in the abdominal cavity, one obtains the best results by dipping the stiffly held fingers suddenly downward, depressing the abdominal walls to varying depths. Bodies can often be felt and outlined in this way that cannot be felt at all by the ordinary method of palpation. Attention should be given to the following points: the location, size, shape, motility, and tenderness of the tumor. Note also any change in position or ease of palpation caused by distention of stomach and colon. In all cases in which it is impossible absolutely to exclude a neoplastic origin for the tumor palpated, the rectum and vagina should be examined. Percussion. — This method is far less valuable here than in examination of the chest, but should never be omitted, and in certain cases exceeds the other methods of examination in value. Its main uses are the determination of the position of the diaphragm, 21 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Abdominal Tumors, Diagnosis the .shape of the upper border of the liver, the pres- or absence of free tluul in the abdominal cav- ity, and the position and approximate size and shape of the stomach and (-(111111 alter they have been dis- tended by gas or fluid. Percussion is the main means of determining the relation of the colon and stom- ach to the tumor found, and what was said under the heading of I aspection in this regard could be repeated here; it might perhaps have been more properly placed here, for percussion is used much more often than inspection for this purpose. Tumors of the abdominal organs caus areas of dulness only when superficially located or of large size, and the resulting area of dulness is always smaller than the tumor. Percussion is valuable in demonstrating thi of areas of dulness normally present. Disappearance or reduction of the hepatic and splenic dulne often of the highest diagnostic value. Disappear- ance of the posterior renal dull In isolated cases auscultatory percussion gives valuable results. .1 iscultation. — Almost no results are obtained by this method. Peritoneal friction, either Idealized or diffuse, is sometimes heard. Arterial and venous tones and murmurs are common and usually- of but little significance. The presence of fetal heart tones is obviously significant. Exploratory Puncture is often 01 the very greatest value, especially in determining the nature of the tumor. The details will be given 'ater. Exploratory Laparotomy. — In certain cases a com- plete diagnosis — i.e. one which localizes the tumor and determines its nature — is impossible even after the most careful examination. In such cases an explora- tory laparotomy is often justifiable, providing it can be made by a competent surgeon under favorable circumstances. Unless the patient presents some obvious contraindication to the operation, it can be done with almost no danger and often gives informa- tion which leads to definite curative treatment. The chemical and microscopical methods of exami- nation can be more profitably discussed in the spe- cial paragraphs referring to the different organs. Before taking up the various diseases of the abdom- inal organs leading to tumor formation, it should be expressly and emphatically stated that any exam- ination of an abdominal tumor which omits a com- plete and careful examination of the entire body is criminally incomplete. Abdominal tumors are often merely synnptoms of diseases of organs remote from the abdomen, and such primary disease can be dis- covered only by T a complete examination of the body. Enlargement of the Abdomen as a Whole. — Thi- may occur as the result of accumulations of gas or fluid in the peritoneal cavity, from large amounts of gas in the intestines, from deposits of fat in the abdominal walls, omentum, and mesentery, and in rare instances from very large tumors. Ascites. — This is the only common cause for extreme enlargements of the abdomen. The abdomen is enlarged in all diameters, but when the cavity 7 is not completely filled, as is ordinarily true, the horizontal diameter when the patient is in the dorsal decubitus will be found considerably greater than the perpen- dicular diameter. The flanks are bulging while the umbilical region is flattened. The skin is often tense and shining, and under it can be seen the overdis- tended veins. Such veins are present in all well- marked cases of ascites irrespective of its cause, but are usually better marked in cases due to atrophic cirrhosis of the liver than in others. The umbilicus is flattened out or even bulging. Sometimes when the patient changes position, one sees the fluid changing position also, and one is reminded of the appe^ r ance of an incompletely filled sack when it is shaken. On palpation the fluid waves can be felt when the hand is placed Hat on one side of the abdomen and the other side is percussed gently. If one lay- the hand lightly over the region of the abdomen which percussion shows to lie tympanitic and at time percusses the Hank, the fluid will flap up strike the hand, i.e. the fluctuation is felt over the Percussion shows dulness over the dependent por- tions of (he abdomen but usually about the umbil ads an area of tympany. The borders of this area are no ir, but wavy. If one outlines thi- area very carefully he will find that though the borders avy, they are at all point ame horizontal plane. When the position of the patient is changed, the level of the fluid changes very promptly to cor- md to the altered position. When tin of the fluid is very great, the entire abdomen will be dull on percussion, even fit the highest level. Auscultation yields no results, except in cases to be stated la Such free fluids in the abdomen are usually transu- but they may be exudates, and the first question is to determine which. Usually thi- can be done with a great degree of certainty even without actual ex- amination of the fluid. If the patient has a perfectly manifest disease of the heart, kidney, or liver, the fluid is very probably a transudate. If there is fluid in the subcutaneous tissues and the other serous sacs also, this probability becomes a certainty. If doubt remains, enough fluid must be withdrawn to ascertain its character. In these cases it is best to remove at first only sufficient for examination, for when the fluid is chylous it is best not to withdraw it except upon the most urgent indications. A trans- udate is a clear, straw-colored fluid, of low specific gravity, less than 1.015, containing a small amount of albumin up to two per cent, and showing almost no cellular elements. An exudate may be equally clear, but is usually cloudy from cells and fibrin. The specifie gravity is above 1.015, usually consider- ably above. The amount of albumin is higher, over four per cent. The cellular elements vary greatly in number and in character, but are always more abundant than in the transudate. The rather rare cases of adipose and chylous ascites show a turbid, milky fluid, very different from the ordinary ascitic fluid. The adipose ascites is usually of high specific gravity, for it is merely an altered exudate, contains a good deal of fat which is in both large and fine droplets, and is free from sugar. The chylous ascites contains fat, but only in fine droplets; sugar is present in most, but not in all cases; the specific gravity is low. When it is settled that the enlargement of the abdomen is due to free fluid, and the nature of the fluid, whether exudate or transudate, has been dis- covered, it yet remains to determine the cause of the trouble. Large peritoneal transudates may come from a disease of heart, kidney, or liver. If due to heart or kidney, the ascites is usually a part of an anasarca; if due to the liver, the ascites exists alone or preceded the edema elsewhere by days or weeks. A well-marked collateral circulation on the abdomen and an enlarged spleen speak for a primary hepatic process, but it may be necessary to withdraw the fluid before the spleen can be palpated. Large exudates in the abdomen are almost always due either to tuberculosis or to carcinoma. The physical signs often differ somewhat from those of the transudate, because as a rule the fluid is not perfectly free and for this reason does not change its level so promptly as does the transudate, and oftentimes certain portions of the intestines become adherent to the abdominal wall, so that tympany is found even over the most dependent part of the abdomen. The clinical differentation of tuberculous from carcinoma- tous peritonitis is often very difficult. If the patient is too young for carcinoma or there is a manifest 25 Abdominal Tumors, Diagnosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES carcinoma or tuberculosis of some organ, then it is easy; but there are many times when it is difficult. The positive reaction to the Koch tuberculin speaks for tuberculosis, a leucocytosis speaks for cancer, but these two sometimes contradict each other. The development of cachexia speaks for cancer. In doubtful cases the patient should be laparotomized for purposes of diagnosis and treatment, if the latter is found possible. There have been numerous instances of confusion of ovarian cysts with free fluid in the abdomen, both transudates and exudates. There is little excuse for this error unless the ovarian cyst is so large as to fill completely the abdomen. Here attention to the history, which in these cases runs back for years, together with the absence of any demonstrable cause for free fluid, will usually enable one to make the diagnosis. As a further* aid one may make an ex- ploratory puncture. The fluid of ovarian cysts presents characteristics to be described in a later paragraph. Sometimes great dilatation of the stomach has been mistaken for ascites, the air and fluid in the stomach giving the same physical signs as free fluid in the ab- dominal cavity. The history of this condition differs from that of the ascites. In cases of any doubt, the stomach tube, by withdrawing any fluid in the stomach, will enable one to make the diagnosis with certainty. Collection of gas in the free peritoneal cavity often causes a very considerable increase in the size of the abdomen, but percussion and the tympany thus de- veloped clearly prove the nature of the enlargement. Whether the gas is in the intestines or in the peritoneal cavity is often difficult to decide when both are possi- ble, as after trauma or in the course of some ulcerative process in the gastrointestinal tract. Here the progres- sive decrease in the size of a liver dulness, known from former examinations to be present, speaks for gas in the peritoneal cavity. It is usually associated with shock and symptoms of peritonitis. Enlargement of the abdomen from fat is common, and is readily recognized, as a rule. We sometimes see lipomata of the mesentery or omentum, which present themselves as tumors of the abdomen and are really such, but it is not to these that we refer. Careful examination of this very common condition will protect one from error. Tumors of the Liver. — The pathological process causing enlargement of the liver may be well placed in two groups, according as the enlargement is diffuse or circumscribed. It must, however, be stated that this division, like most other divisions in medicine, is not at all sharply marked, for most of the patholog- ical processes may occur in either group. For example, amyloid infiltration usually causes a diffuse enlarge- ment of the liver, but may cause sharply circum- scribed masses; while, on the other hand, carcinoma usually causes localized masses, but may cause diffuse enlargements. Diffuse enlargements of the liver, no matter what the cause, bring about no change in the general shape; the liver is, so to speak, merely magnified. The borders lose their normal sharpness and become rounded and thickened. The notch in the anterior border for the gall-bladder is retained. The consistency of the liver is often altered, usually becoming firmer, but sometimes it feels softer. The surface may be per- fectly smooth or slightly granular, depending upon the pathological process in play. A granular surface may be simulated by the presence in the subcutane- ous tissues of partially atrophied adipose tissue, but under such circumstances the granules can be felt all over the abdomen, and they feel more superficial than granules in the liver. Diffuse enlargements of the liver generally take place downward rather than upward. Percussion shows that the upper border of the liver occupies its normal position; presents its normal shape, that of a straight line perpendicular to the surface on which the patient is lying; and shows only a slightly decreased respiratory mobility. Passive Congestion of the Liver. — This is the com- monest example of a diffusely enlarged liver, and inasmuch as the subjective symptoms from which the patient suffers may be, and often are, entirely limited to the hepatic region, the tumor of the liver is often mistaken for some primary condition, while in reality it is not primary but always a mere symp- tom of some disease causing obstruction to the venous circulation at a point above the juncture of the hepatic veins with the inferior vena cava. The subjective symptoms are pain, fulness, ten- sion, and weight in the right hypochondriac region, cither constant or intermittent. These symptoms may, and often do, overshadow all other symptoms of the primary disease. Examination shows a uni- formly enlarged liver, reaching usually only a few centimeters below the costal arch, but sometimes extending to or beyond the umbilicus. The surface is smooth, the borders are regular but rounded. Usually, but by no means always, the liver is tender. Percussion shows a regular upper border with normal respiratory motility. The patients often show a moderate degree of jaundice, usually both conjunctival and cutaneous. The jaundice is practically never intense unless there is some complication. This jaundice is apt to still further strengthen the idea that the patient has a primary disease of the liver. Examination of the ab- domen shows an absence of ascites and no enlargement of the spleen. Exceptionally both these are found, but in these cases the symptoms of cardiac insuffi- ciency are so marked that only the most careless can mistake them. Examination of the chest will in most instances show that the primary disease is oftenest a disease of the heart, endopericardial or myocardial. The cardiac insufficiency may, however, be secondary to some disease of the lungs or pleura, oftenest an emphysema or an obliterative pleuritis. All patients who present an enlarged liver, especially when the liver is painful or tender, should be examined for some disease of the heart, lungs, or pleura as a possible cause for a passing congestion; and if such disease is found, the liver should be regarded as a liver of passive congestion; and this diagnosis should be given up only on the strongest evidence pointing to some other disease causing diffuse enlargement of the liver. Passive congestion of the liver is liable to rapid fluctuations, so that marked changes in the size of the fiver can occur in the course of a few days or even hours. Such fluctuations do not, however, always occur, and the enlargement may remain sta- tionary over weeks and months. Active Congestion of the Liver. — This occurs in a variety of conditions, but is usually of so slight a degree as to pass unrecognized, or if found, is so minimal or so manifestly of secondary importance as to attract, little attention. It occurs in a variety of infectious diseases, the most important examples being scarlet fever, smallpox, the various forms of sepsis, typhoid fever, and malaria. Malaria, especially estivo- autumnal malaria, may cause a marked and persistent enlargement of the liver which may be difficult to diagnose. Such cases may present an icteric dis- coloration of the skin, with marked enlargement of the spleen, thus closely resembling the hypertrophic cirrhosis of the liver, a disease which often gives rise to an intermittent fever resembling the fever of malaria. The differentiation between the two is made by an examination of the blood for the Plasmo- ^\~7* i *3\ due not only to his great <\ "-*»» \ professional skill, but also Fig. 14.— John Abernethy. in ptu't to the singularity of his manners. He used great plainness of speech in his intercourse with his patients, treating them often brusquely and sometimes even rudely A collected edition of his works was published in 1S30." A. H. B. Abietic Acid (C 48 H„0 5 ). — An organic acid, which, in its anhydrous state, chiefly composes common rosin. It also occurs in many other coniferous plants. H. H. R. Abilena Wells. — Dickinson County, Kansas Location. — On a ridge of high land, at almost the exact geographical center of the United States. The wells are about fourteen miles northwest of Abilene, a station on the Union Pacific and the Chicago, Rock Island, and Pacific Railroads. From the report made in 1902 by Dr. E. R. S. Bailey, of the University of Kansas, we glean the following facts: The first well was driven in 1S97, for the purpose of securing drinking water for the animals of a stock farm. It was found, however, that the water obtained at a depth of ninety-five feet was unfit for the purpose. On the other hand, a chemical analysis revealed the fact that it was rich in salts possessing cathartic and diuretic properties; and accord- ingly a company was organized in 1900 for the further development of the property and for the sale and distribution of the water. In 1901 two other wells were bored, and later three additional wells were drilled, all to the depth of 130 feet. At the present time there are over fifty wells, the water of which is filtered through sand and charcoal, to remove a small quantity of suspended matter. As de- livered to the public, in bottles of a convenient size, this water is perfectly clear. The chemical analysis, which was made in January, 1902, by the late Professor Albert B. Prescott, of the University of Michigan, is given below. (In Grains per U. S. Gallon, 231 Cubic Inches, at Maximum Water Density.) Sodium bicarbonate S. 909 Calcium bicarbonate 10.733 Iron bicarbonate 0.917 Sodium nitrate 0. 56S Sodium sulphate 3229 . 2SS Anhydrous. Equal to 7322.648 sodii sulphas, U. S. P. Magnesium sulphate 71 .345 Anhydrous. Equal to 146.139 macnesii sulphas, U. S. P. Calcium sulphate 44 . 966 Sodium chloride 6.5. 176 ,Sili<-a 0.293 Total solids 3432 . 195 " The specific gravity of the water is 1.0G5 at 22.5° C. As seen by the analysis herewith given this water is remarkably rich in cathartic and diuretic salts, and is mildly alkaline with bicarbonates. It is an extremely pure water in respect to freedom from organic con- tamination." Probably the most valuable feature of the Abilena water is its very large content of sodium sulphate in combination with a correspondingly small percentage of magnesium sulphate. The dose, taken preferably one hour before breakfast, is from one-quarter to one-half of an ordinary drinking glassful, equal to about two ounces. This dose should be followed by a liberal drink of table water. Emma E. Walker. Abiotrophy. — From a- privative, /?fos, life, and zpo produce, an abortion or i„i carriage of a woman by artificial means. In a few this applies only to attempts in the cases of women actually pregnant; but inasmuch as crime consists of a combination of a forbidden aci and a wilful and un- lawful intent, it is both reasonable and just that an attempt to produce an abortion should be prohibited even when the woman is not actually pregnant, although she and tin- perpetrator think she is. In many of the statutes will be found saving clauses freeing from criminal liability the person who produces : i miscarriage by artificial means, under circumstances from which it must appear that the fetus is dead or that it is necessary to save the mother. It is suggested as a precautionary measure to any medical practitioner who contemplates arresting gestation, in order to avoid suspicion, to consult some other member of the pro- fession of unquestioned standing, and to obtain the consent or approbation of some one or more of the relatives of the woman. The statute of Pennsylvania is a good example of the best of those passed in this country. It is as follows: 1. "If any person shall unlawfully administer to any woman, pregnant or quick with child, or supposed and believed to be pregnant or quick with child, any drug, poison, or any substance whatsoever, or shall unlawfully use any instrument or other means whatsoever, with the intent to procure the miscarriage of such woman, and such woman, or any child with which she may be quick, shall die in consequence of either of said un- lawful acts, the person so offending shall be guilty of felony, and shall be sentenced to pay a fine, not ex- ceeding five hundred dollars, and to undergo an im- prisonment by separate or solitary confinement at labor, not exceeding seven years." J. " If any person, with intent to procure the mis- carriage of a woman, shall unlawfully administer to her any poison, drug, or substance whatsoever, or shall unlawfully use any instrument or other means whatso- ever, with the like intent, such person shall be guilty of felony, and being thereof convicted, shall be sentenced to pay a fine, not exceeding five hundred dollars, and undergo an imprisonment by separate or solitary con- finement at labor, not exceeding three years." As a practical matter, it is but rarely that the prose- cuting power has the opportunity of invoking this law against a violator of it, for the reason that in all cases of criminal abortion the operation is performed, or the drug is administered, at the request, or it may be the earnest solicitation, of the woman herself, who for this reason is as cautious to avoid detection as is the perpe- trator of the crime. It will be found that almost all of the cases of criminal abortion which have proceeded as far as indictment and trial, are those in which the patient has died from the effects of the operation or the administration of the drug. Even in these cases it has been a rare experience to obtain a conviction because of the secrecy with which this crime is com- mitted, resulting usually in the absence of evidence of those facts which can be used against the culprit. Persons who commit offences deliberately always avoid or destroy those circumstances which are incriminating, so far as is possible. Irrespective of the above-mentioned statutes, both in England and in this country one who administers to a pregnant woman a drug, or employs upon her an instru- ment for the purpose of procuring a miscarriage, in consequence of which she dies, or the child dies after birth, by reason of being prematurely delivered, is guilty of murder. The culprit will be indicted for murder or manslaughter, first because any inferior grade of crime of which he may be guilty will be merged in the felo- nious homicide, which in the eyes of the law is con- sidered the gravest of all offences; and secondly, it may be that a dying deposition has been obtained from the patient. It lias been held that if there be no intent to kill, or to inllict grievous bodily harm, and the means employed lie not dangerou . although used for an unlawful pur- pose, the crime, when death ensues, may be man- slaughter, which is an inferior grade of homicide; other- wise the crime will be murder, and may render the accused, if convicted, liable to the death penalty. It is sugge led. howevi r, thai any known mean-, when used for this purpose, will be dangerous anil should li. considered. This question is really dependent upon the judgment of the criminal prosecutor, for it is always compel, nt for him, unless he is restricted by some statutory provision, to elect to have the prisoner in- dicted for tin' inferior grade of the offence, and abandon, on behalf of the state, the superior grade. When a reputable physician takes charge of a patient upon whom he discovers an abortion has been per- formed, and who subsequently dies, he is bound by law to certify the cause of death to the Health Department. In this it may be necessary for him to disclose the fact of the perpetration of a crime: but is it his duty to in- form the police authorities as soon as he has discovered the (rime? This is an ethical question which need not be discussed here— it is a proposition which each physi- cian should consider for himself. Auxiliary to it is this question: Should he, when the opportunity arises, obtain from the patient a statement which could be used as a dying deposition in a criminal prosecution against the abortionist? Dying Depositions. — For the benefit of the physician who' is willing to aid the State in detecting the perpe- trator of this nefarious crime, it may be stated that if the patient dies and the perpetrator of the abortion is charged with either murder or manslaughter, it will be admissible to offer in evidence the dying declaration of the patient, if she made one. Statements made under such circumstances are entitled to great weight. It hasbeen wiselv said by an eminent English jurist, Lord Chief Justice Baron Eyre, that "such declarations are made in extremity, when the party is at the point of death, and when every hope of this world is gone; when every motive to falsehood is silenced, and the mind is induced by the most powerful considerations to speak the truth; a situation so solemn and so awful is con- sidered by the law as creating an obligation equal to that which is imposed by a positive oath in a court of justice." Such declarations are admissible in evidence only in those cases in which the indictment charges the culprit with the murder or manslaughter of the deceased, and not in those in which the gravamen of the charge is a violation of one of the above-mentioned abortion statutes. The declaration should also be confined to a statement of the circumstances of the death, i.e. the person who performed the operation, the method, time, and place of performance, and such other facts as are germane to these. To render such a declaration admissible in evidence, it is requisite that the declarant should be in actual danger of death at the time it is made, that she should fully realize her impending danger, and that death should actually ensue. It is not necessary that the declarant should state that she realizes that her speedy demise is impending; it is sufficient if it satisfactorily appears from any other circumstances, such as taking leave of her relatives, or receiving extreme unction and the like. If, however, she has any hope of recovers', no matter how slight, such testimony will be inadmissible, though death might speedily ensue. Such a declaration was rejected where the dying person stated: "I have no hope of recovery, unless it be the will of God"; it being held by the court that such statement indicated that all hope had not been abandoned. It need not be under oath, as the solemnity of the occasion is held to be equivalent to the sanctity of an oath. It may be taken orally, but if reduced to writing, it should be carefully preserved and produced at the proper time. It should be confined to a statement of facts, no theories or opinions. 45 Abortion, Criminal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Criminality of the Act. — So far as the culpability of the act is concerned, it is immaterial whether or not quickening has occurred, and whether or not the fetus in utero is dead, unless there is a saving clause in the abortion statute as above stated. The criminality is just as great on the day of conception as at any other period of gestation. Nor is it a defence or excuse to the criminal charge that the mother consented to, or solicited the performance of, the abortion. It has been decided by some courts that a woman who consents to the performance of an abortion is an accomplice, by others that she is not, but this is a purely legal question. The rule of law generally adhered to is, that where a witness is held to be an accomplice there should be some corroboration of her testimony in order to justify a conviction of the accused. Questions in Cases of Feticide. — In every case of feticide the important questions for consideration are: 1. Has the fetus in utcro been destroyed? 2. Has this been produced by natural or artificial causes? 3. If by artificial means, was the act justifiable or criminal? In considering the first question an examination should be made of the clots and other substances ex- pelled from the genital organs, for the purpose of as- certaining if they contain any of the products of con- ception. If the fetus be found it will be necessary to determine, if possible, if it was born alive; if so, its probable age and the cause of its death. A careful scrutiny of it may disclose punctures, wounds, or in- juries which indicate the unlawful use of an instrument. If the fetus is not found the expelled substances should be examined under water, as an ovum, if one is present, is more easily discovered in this way. Nor ought the investigator trust to the naked eye, as much may be lost without the use of a microscope. When the criminal operation is performed in the early stages of pregnancy, the ovum is frequently expelled intact; after the formation of the placenta, the extrusion of the ovum usually precedes that of the placenta, the time intervening being variable, ranging from hours to weeks or months. Did the abortion result from natural or artificial causes? — Both criminal and spontaneous abortion occur generally about the end of the third month. The symptoms discovered will vary with the period of geuch cases the fundus should not be tapped through the vagina, as some I I recom- ud. bul the proper treatment i abdominal section and manual reposition of the uterus. Montgomery A. Crockett. W. A. Newman Dorland. Abrus Prccatorius. — Jequirity, T.m-r Pea, Prayer Beads, Jumble Beads, Crabs Eyes. Abrus L. (fam. Leguminosce) is a genus of six species, related to the lentil and the pea, known to medicine by the species .1. precatorius L., which is indigenous in British India and very widely distributed in the tropics of both hemispheres. The plant prefers a light or sandy soil, and its slender, woody stems climb high over shrubbery in the edges of forests. The fruit resembles a miniature pea-pod, a little more than an inch in length, and contains from four to six seeds. The roots have been employed as a substitute for lic- orice under the name of wild or Indian licorice. The leaves possess the same property, containing con- siderable glycyrrhizin. The seeds are better known than the root, under the name Jequirity. They are a quarter of an inch in length, elongated-globose, smooth, shining, bright scarlet, a black spot surrounding the hilum. A black form, with white spot, and a white form with black spot, occasionally occur. They are largely employed for rosaries, ornamental beads, children's toys, and in India, under the name of retti, (■ ir weighing. They have also been used in India for criminal poisoning, usually of cattle. For this purpose the seeds are crushed and worked into a paste with water. This paste is rolled into a needle-pointed form, mounted upon a.stick and used to prick the skin of the fated animal, which quickly succumbs to heart failure. In South America originated the practice of painting a watery infusion upon granulated eyelids, by which suppuration was induced and the granulations were re- moved. The active agent was at first supposed to be the bac- teria which appear after a time in the infusion. Later, this theory was disproved, and the properties were re- ported to reside in an albuminous substance called abrin. This was later found, by Drs. Sidney Martin and R. Xorris Wolfenden, to be a mixture, and was by them separated into two albuminous bodies, a globulin one- fifth as poisonous as the venom of the common adder and an albumose one-sixth as strong as the globulin. These poisons are destroyed by heat. Their effect re- sembles that of snake venom, the temperature falling greatly and the blood remaining semi-fluid after death. It is by no means certain, however, that this resem- blance is not superficial. Jequirity acts as a powerful irritant to mucous mem- branes. If taken internally, uncooked and concen- trated, it produces vomiting and purgation, the feces being often bloody. Forty seeds produced these symptoms, with partial collapse, but recovery followed. If it is applied to the eyelids, inflammation quickly ensues, with suppuration usually on the third day. The inflammation is characterized by great swelling and pain. If the applications are continued, there is great systemic disturbance also. The applications have been continued by most practitioners for 'from erity of its symptoms, which result from the incn I difficulty in "pointing" and the severity of the coagula- tion necrosis which the toxins of the infecting bacti ri i produce. The symptoms of abscess formation are present, but in a mild form. As the process of destruc- tion and the breaking down of the tissues proceed the boil beer. lues mi|V ;i!ii1 tender nil ] He-- 1 ire. A el'll-t forms over the duct. When it is removed a probe can be passed down into the abscess, even before it has begun to discharge. The suppuration increases, and finalty the core, or the result of the coagulation necrosis, is expelled, when the cavity heals by granulation. This is the natural process without treatment. Since a series of boils may follow in the same indi- vidual, a condition is determined called furunculosis. Constitutional and prophylactic treatment are therefore as essential in many instances as surgical treatment. Frequent baths and changing of underclothing, with scrupulous care of the nails and the avoidance of scratching, are among the preventive measures, while, when the boils are in process of formation, antiseptic washes should protect the surrounding skin. An ounce of sulphonaphthol in a bathtub of warm water makes a mild antiseptic bath that is not injurious and that cleanses the skin of the superficially located bacteria. Boils may be aborted, when they are small and are situated superficially, by applying a few crystals of pure carbolic acid on a glass rod or piece of wood; or, when the disease is further advanced, by the injection into the parenchyma of a three-per-cent. solution of carbolic acid in amounts proportionate to the size of the boil. This method is somewhat painful and not always successful. The expectant treatment should be employed only when a scar is to be avoided and no organ is threatened, and when it is too late for abortive treatment. An anti- septic poultice, gauze or cotton wet in 1:3,000 bichloride solution under a protective, should be applied over the boil and the cavity should be syringed out daily until the core is discharged, when the cavity may be packed and an occlusive dressing (cotton held in place by collodion) applied. The crucial incision will frequently abort a boil and permit an antiseptic in the dressing to reach the seat of infection and destroy the bacteria. When the disease is further advanced free opening, curetting, and sub- sequent treatment as for any other abscess constitute the most rapid and radical method and furnish the best results. Any of these operations can be rendered painless by the employment of infiltration anesthesia or by the subcutaneous injection of a two-per-cent. solution of eucaine B or cocaine. These injections should commence outside the inflamed area, as the increased pressure causes great pain. A carbuncle is the result of an infection by bacteria that enter the skin in the same manner as they do in the case of a boil. The conditions under which they develop are responsible for the difference in the symp- toms and the gangrenous inflammation and sloughing that take place in the subcutaneous cellular tissue. The conditions which predispose to carbuncle forma- tion are the location of the infection in the thicker portions of the skin, where it is difficult for the pus to find a mode of exit, and hence it spreads, causing pressure and coagulation necroses over large areas, and pointing through the numerous columna? adiposae, which offer its only points of exit through the toughened skin. It is distinguishable by the extent of the tissues involved and by the multiple points or heads which 53 Abscess, Treatment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES first show themselves. Pain is not so marked a symptom and is not commensurate with the extent of the suppurative process. The treatment is antiseptic, and always should be in a measure operative to permit the outflow of pus and the action of an antiseptic on the foci of infection. The amount of operative interference demanded varies with the gravity of the case, from a deep crucial incision, with or without curetting and an antiseptic poultice, to complete excision of the entire carbuncle. The latter is of course reserved for the severer cases, while there are varying degrees of operating which depend on the extent of the infection. All parts should be thoroughly exposed and subjected to the action of antiseptics. Felons (panaritium) vary in degree and in their situa- tion. They are abscesses that form in the fingers and hands. The varieties are the cutaneous, tendinous, and subperiosteal, together with a more general form which is known as a palmar abscess and may be either super- ficial or deep according to its relation to the palmar fascia. It is of special importance because it endangers the integrity and function of the hand. The various forms of felon are named according to the structures in which they originate. Their com- plications, sequela?, and gravity depend upon these relations. The subperiosteal felon may destroy a phalanx or involve an articulation. The tendinous felon may spread through the tendon sheaths, and involve these spaces in the hand, if the primary disease is in the thumb or little finger. The cutaneous felon is liable to produce, as are all the others, lymphangitis and possible suppuration in the glands of the elbow and axilla. All of these panaritium cases demand radical anti- septic treatment: early deep incision down to the seat of the suppuration, curetting, antiseptic washing, in many cases packing with gauze wrung out of a 1:2,000 bichloride solution, and the application of an antiseptic poultice till the infection is gone. Prompt treatment of this character will save many fingers and hands that are of the utmost value to those most generally afflicted — the working classes. Carbolic solutions have a tendency to produce gangrene in the extremities and should be avoided in these cases. Bichloride solutions should be employed according to the dermal irritability of the individual. If too strong they may produce an irritation of the skin, and even poisoning. Charles Lester Leonard. Absinthism. — A term applied to the train of morbid symptoms following the abuse of the liquor called absinthe. This is a liquor of an emerald green color, consisting of from forty-seven to eighty per cent, of alcohol, highly flavored with the aromatics, wormwood anise, fennel, coriander, calamus aromaticus, hyssop, and marjoram. The special variety of this drink depends upon the proportions and kinds of these flavors composing it. Its quality also depends upon the quality of its constituents. Since any unpleasant taste may be easily concealed by the strong aromatic used, the alcohol employed in this liquor is frequently very impure. Absinthe, Artemisia absinthium, is the common wormwood, the bitterness of which has passed into a proverb. It is said to contain only one-third of one per cent, of the oil of wormwood, to which are due the characteristic effects of the beverage. The bitter principle of absinthium, absinthin, is a narcotic poison. The coloring matters used in absinthe are often very deleterious; in fact not infrequently cop- per salts have been used in order to produce the green color. Absinthe is chiefly used in France, and especially in Paris. It was introduced there after the Algerian war of 184 1-7 by the soldiers, who, on their campaign, had b sen advised to mix absinthe with their wine as a febrifuge. Its use rapidly increased in France with such disastrous results that it has been described by French physicians as constituting a graver danger to the public than alcohol itself. Symptoms. — Absinthism develops most insidiously, and the habit from the very first seems almost im- possible to break. The symptoms fall naturally into two groups, due respectively to the chief ingredients of the liquor — alcohol, and the essential oil of wormwood which has a special affinity for the brain and nervous system in general. These groups may be subdivided according to their physiological, pathological, and mental effects. The Physiological Effects. — In small quantities the oil of wormwood quickens the heart's action, and in larger ones it is a narcotic. It slightly increases the secretions. Amory, in his experiments with absinthe, found that after its administration the nervous centers, especially the cord, were congested. Magnan found the cerebrum and spinal cord congested. The Pathological Effects. — Amory found an infil- tration of blood in some places in the nervous centers. The heart was soft and flaccid. Phillips states that the membranes of the brain and cord are always injured. The lungs are congested, and extravasations of blood are found in the membranes of the heart. Absinthe drinking is followed by a softening of the brain and general paralysis more often than is the drinking of alcohol. The Mental Effects. — Cadeac and Meunier sum up the mental effects of this drug as follows: Somnolence, torpor, loss of memory, intellectual paralysis, dul- ness, complete loss of will, and brutishness. These effects are, as a rule, observed in the absinthe drinker. Absinthism resembles alcoholism, except that certain features are exaggerated and some new features are added, for absinthe has a marked physical action of its own. The symptoms of absinthism develop far more rapidly than those of alcohol. What has been said of alcoholism can also be said of absinthism: " Alcoholism is primarily a physiological disease comprising: 1. Paralysis of the inhibitory power of the will; 2. A temporary amnesia; 3. A temporary affective and intellective modification of the personality." The effects of a small dose of the drug are giddiness, vertigo, muscular disorders, and convulsive movements like those produced by successive electric shocks. In a stronger dose attacks of epilepsy, more or less violent, occur which are not produced by alcohol. Brunton declares that these convulsions are due to the action of absinthe upon the medulla — not upon the cerebrum. The end is favorable, as a rule, but may be fatal. Corning has investigated the action of absinthe upon the brain and other nervous centers, and confirms this theory. Brunton says that absinthe is a spinal stimulant Absinthe Epilepsy. — Abel says that absinthe gives rise to hallucinations from the very first. States of delirium are often observed between the epileptic attacks, and there may be delirium without epileptic seizures. Marce in his experimental work with animals well established the fact that the principles of absinthe are the agents in causing the special toxic effects noted in absinthism. The epilepsy may develop into acute epileptic insanity; it sometimes occurs without any convulsive attacks. The mania may begin suddenly. The return to sanity is usually sudden, and is accom- panied by forgetfulness of the acts performed. Instead of ordinary convulsive attacks of epilepsy, a person may have a variety of acute mental disturbances. The delirious attacks of absinthism develop suddenly. The symptom-complex appears to be condensed within the shortest possible period. Amory gives a comparative table of the temporary and permanent effects of absinthe and alcoholic bever- ages generally, founded on the experiments conducted by Magnan and himself: 54 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Absorption, Nutritive Absinthe. Animal perfectly well for fifteen minutes, at the least, after the ingestion, with the exception of a few muscular Switchings and a slight uneasiness. Muscular agitation, com- mencing in the anterior portion of the body. No paralysis. Alcohol. In a very few minutes symptoms of inebriation, resulting in torpor. Epileptiform convulsions and rigidity, resulting in a speedy death. No apparent lesion, ex- cept perhaps a slight cerebral congestion, showing the cause of death to be intoxication by the poison. Paralysis, commencing in p o s t e r i o r extremities, and then extending to the anterior. Paralysis of both poste- rior and anterior ex- tremities in succession. No convulsions. Stupor, coma, resolution, and a gradual death. Lesions of the brain and of the alimentary canal; gastritis and enteritis might have supervened, had the animals lived long enough for their development. In general, the effects of absinthe are like those of alcohol, but the former develop much earlier, and arc of a severer nature. In absinthism there is also a more striking disturbance of the nervous system. Emma E. Walker. Absorption, Nutritive. — In the limited sense of this article, and as usually accepted in physiology, absorp- tion is merely the process by means of which nutritive material is taken from the digestive tract into the circulation. [In order that this may be possible, the food must undergo a process of digestion by which the large molecules in the ingested material are broken up into molecules of sufficiently small size to pass through the intestinal mucous membrane into the Iacteals.] Certain fluids when brought into contact with one another will mix until the liquids present a uniform composition, and the passage of the molecules of the one liquid into the intermolecular spaces of the other has been named "diffusion." When the same or similar two liquids are separated by a membrane, this diffusion takes place through the membrane and is then called "osmosis." For a long time osmosis was supposed to be sufficient to account for all the phenomena of absorption, the process seemed so delightfully simple; but careful studies revealed the fact that while dead membranes, fluids, and gases under certain definite conditions obey equally definite laws, osmosis fails to explain the actions of living organs. Theories of electrical action and of differential filtration demonstrate only more clearly the complexity of the function of living absorbing surfaces. Living cells obey their own laws, and they are laws of life, not of mechanics. As the unicellular animal ingests, digests, absorbs, and excretes, and knows what it wants and w-hat it has to do, so in the complex higher animal each cell retains all these functions, while the differentiation of the organs has imposed upon each the additional labor of doing something for the general well-being of the whole organism. The work assigned to the cells of the different parts of the digestive tract concerned in absorption is first to keep themselves in good condition; secondly, to pick out from the contents of the tract such substances as the body wants, and pass them into the circulation. It is safe to assert that normal absorption is a living, not a mechanical act, and that osmosis, as a factor in these phenomena, must not be alone taken into account. In pathological condi- tions, however, in conditions in which the separating membrane has been injured or its vitality lowered, osmosis may well come in as a strong factor in swellings, effusions, lymph accumulations, and all the phenomena usually designated as poor absorption; here we shall have til imagine a fight between the Osmotic and the vital processes, the latter constantly tending In check the action of the former, until recovery takes place ami pure osmotic action has ceased. In a healthy body the skin can be excluded as an organ of absorption; iii spite of the many careful experi- ments made pin and con, I he weight of authority to-day rests with the assertion thai under normal conditions the skin is passive so far as absorption i- concerned. The same must lie said about the muCOUS membrane of the I ith and esophagus, for although we know that violent poisons can be and are taken up by the mucous membrane of the mouth, under ordinary conditions f I docs not stay there long enough to allow of any a I isorp- tion to take place. That limits the absorbing surfaces of the human body to the mucous membranes and allied structures of the stomach and of the small and large intestines. While the nature of the food eaten determines the length of the digestive tract in any given species, the absorbing surfaces bear a definite relation to the bulk of the body and explain why the body stops growing after a certain size has been attained. During a given limit of time the absorbing surfaces increase as their square while the body increases in bulk as its cube. In other words, if we assume that the absorbing surface equals 2, and the body bulk equals 2, then by the time the former has grown to equal 4 the latter equals S; and when the former has increased again to 16, the hitter's bulk is 512. It is easy to see how the growth of bulk is checked by the limitations of the absorbing surfaces. The substances to be absorbed are peptones, glucose, and emulsified fat, the products of digestion, besides water and different salts which have remained unchanged. The stomach has no specialized organs of absorption, but its whole mucous membrane may, under certain conditions, absorb materials digested in its cavity, peptones and glucose. The older view which made the stomach practically the only organ worth mentioning of the digestive tract, and took it for granted that its function in the absorption of peptones, glucose, salts, and water was of proportionate importance, has been slowly changed by the results of modern experiments. Without going to the other extreme view which makes the stomach merely the temporary receptacle for food, these experiments prove that absorption of the above named substances may take place, but only to a limited extent. Of the carbohydrates, dextrose, lactose, maltose, and saccharose, even dextrin, may be absorbed by the mucous membrane of the stomach, and the more concentrated the solutions, the more marked is the absorption. Peptones are absorbed slowly and appar- ently with difficulty, while condiments and alcohol increase distinctly the absorbing power of the stomach. Perhaps the most interesting and least noticed fact brought out by these experiments is that practically no water is absorbed by the stomach, but that all passes into the intestines; on the other hand, alcoholic solu- tions are readily taken up. This fact may ultimately help to explain why water is the beverage most desired when men are thirsty, and why something mixed with the water seems necessary when people, not thirsty, gather and drink for social enjoyment. Peptones, glucose, and emulsified fats are absorbed mostly in the small, and to a limited extent in the large intestines. Throughout the large and small intestines w-e find organs specialized for absorption, viz., the villi and the solitary glands. The former are most numer- ous in the duodenum and jejunum, the latter in the ileum. Throughout the large intestines we find solitary glands, but no villi, irregularly scattered, the largest numbers in the cecum and appendix vermiformis; and their limited number, together with the well-known high absorbing power of the large intestine, leads us to think that its mucous membrane is an important factor in absorption. The villi, little cone-shaped protuberances in the 55 Absorption, Nutritive REFERENCE HANDBOOK OF THE MEDICAL SCIENCES mucous membrane, have a dense network of blood capil- laries just underneath their epithelial covering, while a lacteal duct occupies the center of the cone. The soli- tary glands have a dense lacteal plexus beneath the membrane and a limited supply of blood capillaries. All the blood capillaries of the intestinal tract are radicles of the portal vein, while the lacteal ducts are radicles of the abdominal lymphatics. The villi, however, are the principal organs and carry the bulk of the peptones and sugars into the circulation directly, while the emul- sified fats absorbed are poured by the way of the lac- teals and abdominal lymphatics into the cisterna chyii, and from there through the thoracic duct into the left subclavian vein. How much the peptones absorbed are changed in their passage through the epithelial cells of the villi, and how much additional modification takes place in the capil- laries and veins before the absorbed material enters the liver, is as yet a matter of conjecture. [The modern teaching inclines, however, to the theory that the pep- tones as such are not absorbed, but are further split into aminoacids which are synthetized in the columnar cells of the villi into serum-globulin and serum-albumin and in this form the protein is carried to the tissues.] The knowledge that everything ingested, with the exception of fat, and water enough to emulsify the fat, has to pass through the liver before the body can make use of it, will probably increase our respect for that long-neglected and much-abused organ. The emulsified fats are split up into fatty acids and glycerin which are taken up by the epithelial cells and passed into the stroma of the villus, there to be recon- verted into minute fat globules. Whether these now pass directly into the delicate lymph channels which traverse the villus and finally unite to form the lacteal, or whether the lymphocytes, so abundantly found in the stroma, carry the small fat globules from the epithelial cells directly into the lacteal, is yet an unsettled ques- tion. Under ordinary conditions only fat enters the lacteals, while peptones and sugar find their way into the blood capillaries; but that does not preclude the possibility that after an excessively fat meal, a trace of fat can find its way into the blood capillaries, as well as that, in cases in which an excess of meat and carbohy- drates has been eaten, a trace of either can be found in the lacteals. [The carbohydrates of the food are converted into the small-molecular glucoses which are taken into the radicles of the portal vein and pass into the liver.] The absorbing power of the small intestine is about equal to the task of taking up the quantity of fluid formed by the action of the digestive ferments plus the quantity of fluids secreted by the pancreas, liver, and intestinal glands, and thus, as these quantities com- bined do not represent the total amount of fluid present, the contents of the small intestine remain fluid through- out its entire length. In the large intestine the conditions change, the absorbing power is high, secre- tion and digestion are limited, and, as a consequence, the contents become more and more pasty as they near the rectum, until finally the feces contain that portion of the food ingested which has escaped digestion and absorption. The absorbing power of the large intestine is not limited to substances prepared by the action of the digestive fluids, but it can absorb undigested food, such as white of egg, although it is probable that even here there is a splitting up of the protein molecule into smaller molecules before absorption takes place. Nutri- ent enemata, based upon this knowledge, have saved the lives of many patients. The final test of the activity of absorption as well as of digestion is a chemical ami physical examination of the f sees, for the details of which the reader is referred tn the article cm Fir,:,, crniui 'nation fftlir. Julius Pohlman. Abstracta. — Abstracts are solid, powdered prepara- tions, no longer official. They were introduced into the United States Pharmacopoeia of 1SS0, and were believed to have advantages not possessed by the ordinary ex- tracts, which latter preparations they were designed to supplant. However, in spite of certain good qualities, they did not come into general use; and in subsequent revisions of the Pharmacopoeia they were not retained. Abstracts possessed the advantage of definite and uni- form strength, each gram of the abstract being equal to two grains of the crude drug or fluidextract. The advantages of the abstracts are given by Remington, as follows: "(1) Each abstract represents twice the strength of the drug or fluidextract from which it is prepared. (2) They are dry powders, if properly made, and thus are permanent and portable; not sub- ject to precipitation as fluidextracts are; not liable to become hard, tough, and variable in strength, as is the case with extracts. (3) Injurious exposure to heat is entirely avoided, and the official process of 1SS0 requires no apparatus but such as either is at hand in the phar- macy, or can be easily obtained by a pharmacist operat- ing on a small scale. (4) The final thorough tritura- tion of the dry powder reduces the soluble and active constituent of the drug to a pulverulent condition, the diluent is soluble, and the fine state of division of ab- stracts is the most favorable condition that a powder can possess to secure efficient medication." Eleven abstracts were official in the U. S. Pharmacopoeia of 1S80. R. J. E. Scott. Abulia. — From a- privative, and flo>Sk-q, will. Paralysis of the will, a condition in which the subject has lost the power of decision or initiation. It may be mistaken for paralysis in certain extreme cases, but the power of movement is present, the motor impulse only being in abeyance. Abulkasim. — (Abul Kasim Chalaf Ben Abbas el- Zahrawi.) Arabian physician and surgeon born in Zahra near Cordova, Spain. The exact dates of his birth and death are not positively known, but he flour- ished in the tenth century and was physician to the Caliph Abd-el-Rahman III. According to the Arabian chronicles he died in the year 1013 at the age of 101 years, so that the year of his birth was 912. No details of his life are known. The first part of his compendium of medicine (" Altasrif") was published in Latin in the sixteenth century as Liber tkeoricm nee non practices Alsaharavii i Augsburg, 1519). The second, surgical, part was published at Venice in 1497: a Latin transla- tion appeared at Basle in 1541; an edition in Arabic and Latin, edited by Channing, was published at Oxford in 1778. A. H. B. Acacia. — Gum Arabic, Gum Acacia, Gum Senegal. "A gummy exudation from Acacia Senegal Willd. and other species of Acacia (fain. Leguminosa)" (U. S. P.). In roundish tears, often an inch or more in diameter, transparent, except for the whitish fissures, of a glassy, veiny, or fissured fracture, ranging from nearly colorless to a deep reddish- yellow, nearly tasteless and odorless, wholly soluble in two parts of water, to form a thick mucilage of a faintly acid reaction. The official article is re- stricted to a color not darker than "pale amber." The presence of starch in powdered acacia is detected by a blue color on the addition of iodine, that of dextrin by a red color. A pure solution will not be affected by neutral lead acetate. This gum was formerly yielded by other species of Acacia, notably -4. vera Willd., and the very finest gum of commerce still proceeds from this species. It is chiefly in smaller tears, which are more brittle and broken, and less translucent and glassy, owing to the much more numerous fissures. Both species are small thorny trees of northern Africa, A. vera more abundant in the eastern, A. Senegal in the western districts. The gum is a decomposition product from cellulose and is more abundantly pro- 56 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acanthosis Nigricans duced by unhealthy trees. It exudes from natural fissures and artificial incisions. Gums practically equivalent to acacia are produced by species in related genera. An excellent article is produced by species of Proaopis, growing in the southwestern United States, and known as Mesquit gum, bu1 the supply is too irregular to be utilized. Some of these substituted articles, as, for example, Ghatti gum, are very inferior. The varieties of acacia are now little known by the locality-names formerly applied to them, the grading being done almost wholly by number, the quality depending upon whiteness and solubility. The pure gum consists wholly of com- pounds of arabic acid with potassium, calcium, and magnesium. Acacia has no physiological action, except that of a mechanical demulcent. Its pharma- ceutical uses, as an excipient, for emulsionizing, and for suspending insoluble substances or those the acridity of which it is desired to mitigate, are very numerous and important. Henry H. Rusby. Acanthaceae. — (Acanthus family). A large family, related to the Mints and Vervains, but unimportant except for its very rich ornamental properties. Many species have been utilized in the materia medica of British India, and the properties of Adha- toda (see Vasicine) are very peculiar. The principles are mostly resinous and amaroidal, with a few- alkaloids, and all the recorded actions and uses, except those of Adhatoda, are rather indifferent. H. H. R. ■Want hia. — A genus of true bugs, Hemiptera, para- sitic on birds. These insects are sometimes introduced into human habitations and attack man. They are serious house pests in some parts of Mexico. See Insects, parasitic. A. S. P. Acanthocephala. — A suborder of nematode worms which have no alimentary canal. The adult stage occurs in the intestine of vertebrates, as a rule those which live in or near water; the larva are found in the bodies of certain invertebrates, very frequently small Crustacea. All these worms possess a retrac- tile proboscis armed with rows of hooks by means of which they cling to the intestinal wall of their host; hence they are called "hook-headed worms." The genus Gigantorhi/nchus occurs commonly in pigs, mice, rats, etc., and has been reported in man; Echi- norhynchus has also been taken from the human intestine. See Nematoda. A. S. P. Acantholysis Bullosa. — This rare dermatosis, known formerly as epidermolysis bullosa hereditaria, is a typical familial anomaly, capable of being perpetuated through several generations, manifest in infancy or early childhood and insusceptible of modification by treatment. Like urticaria factitia and hemophilia it is a predisposition only, requiring slight external irritation to become manifest. As some eases occur in isolated individuals the adjective hereditary cannot literally be used to designate the affection as a whole. A comparatively new disease, acantholysis bullosa has very probably masqueraded in past years as pemphigus, or as a simple idiosyncrasy, since it is obvious that very slight irritation will raise blisters on certain subjects. The bulls which characterize the disease vary considerably in size and aside from a slight tendency to hemorrhage present no peculiarities. They tend to appear wherever the clothing bears or rubs against the skin (neck band, wrists); on pressure surfaces where ordinary blisters and callosities tend to form; over the knees and elbows, because these joints when flexed serve for support, and at the site of chance knocks, etc. It is asserted confidently that blebs never appear spontaneously. In cases in which patients use certain members habitually a sort of occupational disease may !)!• set up. A draughtsman constantly holding a pencil bet ween his fingers and thumb may suffer from an almost Continuous forma- tion of bulla' where the implement presses He may even as a result undergo slight atrophy of the linger lips and lii-s of the nails. Under ordinary circum- stances no permanent changes occur beyond possible slight scarring and pigmentation, with alopecia in hairy regions. A rare sequela is miliary retention cysts from occluded sweat glands. Nothing is known of the nature of the affection. Certain features suggest a vasomotor lability, such as underlies a number of other superficial affections. The trauma acts upon the supposedly irritable blood- vessels and causes an effusion into the rote. Treatment may be summed up in protection of exposed areas as far as practicable. Acanthoma Adenoides Cysticum. — This affection of the skin, to which many designations have been applied, is most commonly spoken of as multiple benign cystic epithelioma or simply benign epitheli- oma. It is characterized by the formation of insensi- tive tubercles or nodules, which are at first of pin- head size and seldom exceed that of a pea. They resemble very much a beginning epithelioma, having the same pearly appearance, varying to pinkish or yellowish. They are, however, numerous as a rule; and, usually discrete in distribution, are at times clumped together. They usually' occur on the face, especially the central portion, including the eyelids, root of the nose, lower part of the forehead, and cheeks, but are sometimes seen on the trunk and arms. Their growth is slow, and has a well defined limit. More or less colloid transformation may ensue. Firmly embedded in the skin, they cannot be shelled out and when punctured only a little serum or blood escapes, unless colloid degeneration has occurred. In rare cases in which epithelioma has developed in these growths there may have been no actual transition from benign to malignant, for this is always extremely rare in benign growths of any sort. In the recorded material are a number of instances of familial incidence, but this is not the rule. The affection occurs irrespective of age and sex, but has some tendency to appear at puberty. Some forms have evidently been classed as varieties of the acne of puberty, for both milium and comedones may be closely simulated during the onset of the affection. According to a number of authors some of the cases reported as belonging to this affection should have been lymphangioma tuberosum multiplex, an un- related dermatosis having only a possible clinical resemblance. Benign epithelioma is purely a neoplasm, the etiology and nature of which are no clearer than those of other benign growths. Histologically it is com- posed of formless masses and long processes of epithelial cells not unlike those seen in true epitheli- oma. Cell nests or pearls are to be found. The irre- sponsible arrangement of the cells suggests an origin from misplaced embryonal residues. We are entirely in the dark as to how formations so generally resem- bling true epithelioma can be benign, but the latter is a disease of the degenerative period of life, while benign epithelioma usually develops at puberty. Practically there is hardly any chance of confounding the two affections in the clinic. When benign epithe- lioma is removed with the curette, incision and evacuation, or electrolysis, there is considerable tendency toward recurrence. The affection should not be confounded with molluscum contagiosum, simple colloid degeneration of the skin, or cysts of the sweat glands (hydrocystadenoma). Acanthosis Nigricans. — Synonym: Dystrophie pap- illaire et pigmentaire (Darier). A disease of the skin and mucous membranes characterized by 57 Acanthosis Nigricans REFERENCE HANDBOOK OF THE MEDICAL SCIENCES hyperpigmentation and papillary hypertrophy, devel- oping, in the majority of cases, in the course of an abdominal cancer. The first recorded case of this disease occurred in a patient in Unna's Clinique for Skin Diseases in Hamburg, and was described by the present writer in the "International Atlas for Rare Skin Diseases," No. 4, Plate X., in 1889. Since then cases have been observed in nearly all the countries of Europe and in this country. Couillaud, 1 in a monograph pub- lished in 1S9G, was able to record thirteen cases. In 1909 the writer was able to report' fifty-two cases of the disease collected from the literature. The disease usually begins with a slaty or brownish discoloration of the skin of the neck, about the genital organs, and the umbilicus. In other cases the first symptom to attract the patient's attention is the papillary or condylomatoid proliferation affecting the mucous membranes of the mouth. Other regions that may be affected are the flexor surfaces of the extremities, the axilla?, and the inframammillary region, the anal region, and in women the vulval and vaginal mucosa? A. striking feature of the distribu- tion of the disease is its almost perfect symmetry. The pigmentation varies from a light gray to a bluish-black in color. It occurs over large areas and fades at their borders into the normal color of the skin. It is generally coextensive with the papillary hypertrophy, but sometimes appears as a precursor of this condition. It has never been noticed on the mucous membranes. The papillary hypertrophy varies in degree from a slight prominence of the normal areas of the cuticle to warty excrescences that may attain an elevation of a centimeter. It occurs in extensive patches in the regions noted and its borders merge insensibly into the normal skin. The patches are always dry, there is no exudation even from pronounced filiform excrescences, and they impart a harsh grating sensa- tion on palpation. On pinching up the skin the epidermis is seen to have lost its elasticity, but the affected regions are freely movable over the subcutis. There is no appreciable desquamation from the affected areas. On the mucous membranes the papillary elevations may be discrete or they may occur in patches. The excrescences sometimes attain a very considerable size, and in appearance and con- sistency are strikingly like venereal warts, but, unlike them, do not bleed readily on palpation. In some cases of long duration, changes in the appendages of the skin have been noted. The nails of the fingers and toes become dry, cracked, and mis- shapen. The hairs on the head and over the entire body become dry and fragile and may fall out spon- taneously, producing a total alopecia. Anatomy and Pathology. — Under the microscope changes corresponding to the clinical picture are found. The horny layer appears somewhat thick- ened; the granular layer shows several rows of keratohyaline cells; the rete Malpighii is the seat of an hypertrophy which in some sections attains the enormous dimensions seen ordinarily in common warts, and its lowest layer contains great quantities of pigment. The papilla? are elongated, sometimes attaining a length of six or eight millimeters, and often ramify, following the digitations of the epithe- lium above them. They show no evidence of increase in width. The subpapillary layer and the cutis itself show but very slight changes — a moderate increase in the number of emigrated cells, of mast and pigment cells. In considering all the cases recorded we may divide them into two groups: those occurring in children, the juvenile type, and those occurring in adults. In the juvenile type, about one-third of the known cases, the disease once established remains stationary and the patients seem to suffer no inconvenience except from the disfigurement. In the adult cases, that is, those developing after the age of nineteen or twenty years, an abdominal cancer has been found or strongly suspected on clinical grounds in a pre- ponderating number, not less than eighty per cent. In the two cases in which an autopsy was obtainable there was an extensive carcinosis of the abdomen, which, while it spared the adrenal bodies, was especially noted as involving the lymph glands in close proximity to the large sympathetic ganglia. There is little doubt but that the disease is directly dependent on the existence of abdominal cancer, but whether it be a cutaneous manifestation of a peculiar cancer intoxication or w-hether it be due to changes induced in the great sympathetic ganglia through the pressure of the tumors on them, or to the com- bined action of both these causes, is a matter that future investigation must determine, but from the fact that acanthosis nigricans does not occur in the vast majority of cases of cancer, it seems reasonable to ascribe the disease to a special localization of the tumor which deranges the functions of the sympa- thetic ganglia and the adrenals. In the juvenile cases there is some ground for assuming a similar action through benign tumors, connective-tissue bands, etc. i Diagnosis. — Ichthyosis, pityriasis rubra pilaris, and keratosis folliculorum (Darier's disease) are the only diseases which may bear even a remote resem- blance to acanthosis nigricans. Ichthyosis is a mild congenital disease, persists throughout life without producing any general disturbances, is most pro- nounced on the extensor surfaces, never affects the mucous membranes, and is characterized by constant desquamation in more or less extensive scales. Pityriasis rubra pilaris, sometimes occurring in extensive sheets about the great flexures and pre- senting the peculiar discoloration common to many hyperkeratoses, may suggest acanthosis nigricans, but in all other respects there are more points of difference than of resemblance between the diseases. Darier's disease is differentiated by the limitation of the affection to the follicles, the non-involvement of the mucosa, the peculiar greasy character of the affected surfaces, and the occasional occurrence of large nodular masses from which a foul secretion is dis- charged. The differentiation from the various pigmentary affections of the skin need not be entered into. The prognosis of the disease in the adult cases is, of course, that of the underlying cause — the abdominal cancer; that is, it is hopeless. In some of the cases the cutaneous manifestations have undergone a varied course, probably depending upon changes in the location or size of the tumors in the abdomen. In one typical case the cutaneous lesions disappeared in the course of six months after a radical operation for malignant deciduoma. In my own case there was an almost complete disappearance of the affection of the skin and mucous membranes shortly before the patient died. Sigmund Pollitzer. References. 1. Couillaud: Dystrophie pap. et pig. ou acanthosis nigricans, Paris, 1896. 2. Pollitzer: Journal Am. Med. Assoc, Oct. 23, 1909, vol. liii., p. 1369. Acapnia. — From a- privative and na-rvbi, smoke, vapor. A condition in which the amount of carbon dioxide in the blood is reduced below the normal. This may be produced voluntarily by taking a number of deep and rapid inspirations; the carbon dioxide in the blood is thereby reduced in amount, and as this gas in the blood is the normal stimulus to the respiratory center, the result is apnea. Persons who are obliged to hold the breath for a long time, such as the pearl divers <>f Ceylon, are aware of this effect of rapid breathing and make use of it in their occupation. The respiratory paralysis sometimes occurring under ether anesthesia is attributed by Yandell Henderson 1 to ;,.s iference Handbook OF THE lEDICAL 5CIENCES. Plate IN Fig. 2. Shows the discoloration about the lips and chin, and the condylomatoid proliferation at the angles of the mouth. H Fig. 3. Microscopic section through one of the condylomatoid masses at the mouth. Acanthosis Nigricans. "Case of Dr. S. Pollitzerj from the International Atlas of Rare Skin Diseases.' REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acclimatization acapnia induced by the excessive pulmonary ventila- tion in the primary excitement occurring in unskillful etherization. The same investigator 2 attributes the shock after operation largely to acapnia resulting from hyperpnea during beginning etherization. He holds also that the cessation of peristalsis when the abdomen is opened is due to local acapnia from direct exhala- tion of CO,, this being still further increased by laying hot damp" clothes over the intestine. Again the uterine contractions of normal labor, he thinks, arc stimulated by the normal carbon dioxide content of the blood; and the ineffective pains of tedious labor arc due in large part to rapid breathing and the con- sequent acapnia. The conclusion at which he arrives as a result of numerous observations is that "C0 2 tension in the nerve centers and in the tissues and fluids of the body is a factor in the maintenance of tonus (in the broad sense of the word) of the same order of importance, as temperature, oxygen supply, osmotic pressure, and the equilibrium of anions and cations." (See also Anesthesia, general surgical, sec- tion on the Role of carbon dioxide. j T. L. S. References. 1. Surgery, Gynecology, and Obstetrics, August, 1911. 2. American Journal of Physiology, April, 1909. Acardius. — See Teratology. Acarina. — Acarida. An order of mites of the class Arachnida. These arthropods are of small size, are usually ectoparasitic in habit, and their structure shows some degeneration. The order includes a number of species which cause various dermal dis- orders. Among the most important families the following may be mentioned: Detnodicida:, par- asitic in hair follicles; Sarcoptidw, the itch-mites of mammals; Ixodidw, the ticks temporarily parasitic on terrestrial vertebrates. Mites usually hatch from eggs in an immature condition and undergo a meta- morphosis. See Arachnida. A. S. P. Acaroides gum.— See Xanthorrhcea Resin. Acarus. — An old name for the genus Sarcoptes which includes a number of species of itch-mites. S. scabiei bores galleries in the human skin, pro- ducing itch, and may also be a cause of eczema. See Arachnida. A. S. P. Acinesia Algera. — A condition characterized by pain on movement. This is purely a symptomatic designation and has little clinical significance. Most of the cases previouslj' called by this name are of patients suffering from myalgias, indurative myositis, or intermittent claudication. S. E. J. Accidents. — See Injuries, and Workingmen's Com- pensation Acts. Acclimatization. — When an3>- animal, brute or human, is removed from the environment to which he and his ancestors have long been accustomed, a con- siderable disturbance of the whole economy is liable to ensue. The process of evolution has developed certain organs and certain functions in accordance with the requirements of those circumstances under which his race has found itself, and when he is sud- denly transplanted into new conditions some of his faculties become without occupation, while others hitherto uncalled upon, and therefore undeveloped, are suddenly subjected to a demand to which they are quite unable to respond. The process of accommoda- tion of the individual to new conditions of climate is known as acclimatization or acclimation. No other animal is so facile in his accommodation to changes of climate as man. The lower animals and plants often do not recover for several generations from the effects of transplantation. The Society d'- Acclimatisation of Paris has for years been rallying on, in its gardens, an extensive zoological experiment on the domestication of foreign animals and plants which it is believed can be made useful to European countries. The re >:>° N. latitude, Euro- peans acclimate much less readily than in the same latitudes south. Algiers, for instance, is vastly more difficult for the European to live in than < ape ( lolony, yet both places are about latitude :i.">°. The Argentine ( 'mi federation and New South Wales are more healthy than the East and West Indies, which are of the same latitude. The mortality of the French and English troops has been found to be about eleven times as great at foreign stations in the northern as at those in the southern hemisphere. The chief cause of the dif- ference is in the prevalence of miasmatic fevers so deadly to Europeans. Those fevers in the northern hemisphere occur even in high altitudes, while south of the equator they do not extend beyond the tropic. The island of Tahiti, for instance, about latitude 18 S., is quite exempt from these fevers. The records of the French and English soldiers on foreign service show, in South America, a sickness from malarial fevers of L.6 in 1,000 men per annum; while in a similar latitude in the northern hemisphere, the number of such cases annually is 224 per 1,000. To the question, "Can Anglo-Saxons ever become completely acclimatized in the tropics?" a more or less guarded negative reply has been given by proba- bly a majority of the most eminent authorities. This, it will be observed, does not mean that Anglo-Saxons cannot live in the tropics under conditions of special caution. It does imply, in the minds of its advocates, that Europeans can never expect to perform the same work under the same conditions as the natives. If this be the case, it presupposes the continuance of a distinctively menial or servile class as a permanency, which appears to be inconsistent with the theory of a purely democratic colony. In favor of the pessimistic view regarding tropical acclimatization are urged the high death rate, the physical deterioration, and the reduced fertility of Europeans in the tropics. The first two of these considerations are certainly matters in which the improved sanitation of recent times may be expected to count for much. In fact, the annual mortality of European troops in India, which prior to 1S59 had been 69 per 1,000, had fallen in thirty years to 12 per 1,000. The death rate of European children in India is considerably less than that of native children, and in some colonies compares favorably with that in many districts of Europe. Whether, as has been sometimes claimed, white families in the tropics are likely to die out, is difficult of demonstration, because the stock is liable on the one hand to be reinforced by fresh European immigra- tion, or on the other to be deteriorated by mixed marriages. But a paper presented at the Seventh International Congress of Hygiene and Demography by Sir Clements Markham shows that families of pure European blood had been settled in tropical places for more than two centuries without any deterioration, mentally or physically, of the later, as compared with the earlier representatives. Regarding fertility as affected by removal of Euro- peans to the tropics, great diversity of opinion has existed. The analogy of plants seems to sugge-t a loss of fertility, at least temporarily, from a change of climate. For example, the chrysanthemum is said to 59 Acclimatization REFERENCE HANDBOOK OF THE MEDICAL SCIENCES have remained infertile for sixty years after its trans- Elantation from China into France, so that the seed ad to be continually imported. But after that time fertility began to be regained, till now the species propagates itself. European fowls, which when first- brought to Bolivia became sterile, later regained their fecundity. Regarding the human species, however, we are lia- ble to error in judging from cases in which infertility is due to crossing of the breed with inferior races; or when possible lack of fecundity is overcome by fresh European admixture. Yet, as against a permanent sterility of pure European families in the tropics there are abundant instances. It is said that Spanish women in Guayaquil, at a temperature rarely below S3 F., are exceedingly prolific, and that the French have a higher birth rate in Algeria than in France. In general, we may say that it is not temperature or climate intrinsically which is the obstacle to acclima- tization. Physiology has shown the marvellous adaptability of man to withstand the widest ranges of thermometric variation. Moreover, anthropologists agree that mankind is all descended from one primi- tive stock. Hence man has acclimatized himself, as a matter of fact, wherever by successive migrations he has permanently occupied new fields. The principal climatological changes to which one must accustom himself in making a change of residence may be divided into those of (1) barometric pressure, (2) humidity, and (3) temperature; of these the last are by far the most important. 1. Barometric Pressure. — Leaving out of account, of course, conditions of increased atmospheric pressure which are usually artificial (see Caisson Disease) and if not, as in removing from a high altitude to a low one, are of little practical importance, we pass at once to phenomena accompanying change to a rarefied atmos- phere, as in removing from the sea-level to a mountain- ous locality. Persons with sound hearts and arteries usually experience little difficulty in accustoming themselves to altitudes of 6,000, 7,000 or even 10,000 feet. Many of the most thriving cities on our conti- nent are at such heights and the inhabitants suffer no inconvenience. Mountain climbers inure themselves to elevations of upward of 20,000 feet. On the other hand, people with weak cardiac muscles may be incapacitated at elevations of 3.000 feet or less. Tuberculous patients visiting high altitudes for cure are probably somewhat more prone to pulmonary hemor- rhages than if they had remained at a lower level. The main precaution to be observed for those who find the increased respiratory rate embarrassing is to keep perfectly quiet for a time and then to begin exercise only with great moderation. Usually, unless the cardiac insufficiency is considerable, they cam gradually work up to a degree of activity equal to their fellows. If they return to a lower level, however, and from thence go back to the higher, the same pre- cautions must be taken as in the original instance. 2. Humidity. — This is generally far greater in the tropics during certain seasons than in temperate zones. It generally goes hand in hand with the amount of rainfall, which sometimes, in the Philippine, for instance, rises as high as eighty inches in two successive days. Independently of the fact that a high humidity makes heat more oppressive, great moisture is liable to aggravate rheumatic affections. The dangers of high humidity are of course largelv unavoidable, but one should, if possible, make his entrance to a tropical region in the dry rather than the rainy season. 3. Temperature Changes. — These may be in the direction of either a colder or a warmer climate. Regarding the former, lit lie need be said. Apart from cases of starvation and freezing, Arctic explorers usu- ally endure cold very well. The facility of the acclimatization of the negro even to the far north is shown by the fact that among the few men who accompanied Peary nearly or all the way to the north pole was a negro. Abundant clothing and food of a high caloric value, especially fats, are the obvious and chief fortifications against cold. Four thousand or more calories per day are requisite for an adult. Acclimatization against Hot Climates. — With the great expansion in late years of our country's colonial possessions, tropical acclimatization has assumed an importance greater than ever before, and fortunately nearly coincidently with the acquirement of new territory, new knowledge has come to us of how to meet many of the dangers hitherto so fatal. First under this head we naturally think of the effects of heat, per se. The precautions to be ob- served here differ only in degree from those we are familiar with as necessary in our summers at home. Avoidance so far as may be of the direct rays of the sun, through keeping in doors in the middle of the day, is made easier by the tropical custom of suspending business for three or four hours about noon and con- cent rating work in the morning or late afternoon. Pleasure-seeking is naturally confined to evening hours. The pith helmet, the umbrella, and the ha- bitual use of the shady side of the street (if any) are natural protections against heat stroke and sun stroke. Quite as important is a dietetic regimen which will supply less calories than are needed in a temperate clime. Two thousand or less calories should suffice the average adult. Rice as a staple of diet has long approved itself in hot countries. Fruits and vege- tables may largely replace protein and especially fat foods. Alcohol, especially in its stronger forms, should be avoided or minimized. The free use of spirits by Englishmen translated to India has long been a by-word as a contributor to sickness. Care must, however, be exerted in the use of drinking water for reasons which will shortly be considered. We come now to the greatest dangers in the way of warm acclimatization. These are from diseases many of them caused by protozoa which find inter- mediate hosts in insects. First of these in importance is the group of malarial diseases. It is these that have made large tracts of the earth uninhabitable to white men for centuries. While the typical tertian, double tertian, and quartan types, characterized by more complete periodicity, are found in many temperate climates it is the sub- tertian, or estivoautumnal type which manifests the greatest malignancy and this is practically limited to tropical and subtropical climates. In all kinds of malaria, however, the microorganism penetrating to the blood-corpuscles develops asexually and with the pouring forth of the new-formed organism after the rupture of the blood-cell, comes the chill. The sexual propagation of the various parasites takes place generally in the body of the mosquito, which sucks out the parasites in the action of biting a person who carried them. After undergoing develop- ment in the mosquito they are again injected into the next person when that insect bites. It is the Anophelina: alone among mosquitos which carry the malaria parasite. They take it from man and recarry it to man. The aim in preventing this infection is therefore to protect from this mosquito. If this protection is made complete the otherwise deadliest malarial swamp will be perfectly safe. In the attempt to fortify every portion of the line one seeks: (1) To limit the malarial-bearing pabulum of the mosquito by treating all infected persons with quinine to kill off, as far as possible, the organisms from their blood. (2) To prevent the mosquito from hatching by (n) removing by a drainage-system standing water where they may breed; the cultivation of soil also tends to absorb standing water; ('0 when water cannot be got rid of, by covering its surface with petroleum, so that any larva; may thus be killed; (c) screening 60 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acclimatization houses and also beds so thai any mosquitos if they are hatched and then become infected, they cannot bite another individual; (ii pediculi and also by certain species of ticks. Another, i he African relapsing fever, is definitely known to be conveyed to man by a specific tick, so that the dis- ea e i^ called "tick fever.'' Prophylaxis for Euro- peans is easy because the I iek cannot climb a smooth surface and if bedclothes are kept from touching the floor the insects cannot get upon a bed, and they do not bile by day. Resting or sleeping in a native hut, however, should be avoided, as the ticks might get upon the clothing. The acclimatizing European must be especially careful of the drinking water and it is safer to drink only bottled or distilled water till he can have the benefit of a careful examination of the local supply. Among his dangers from this source are the ingestion of Amoeba coli. This is a common cause of tropical dysentery and it may leave the intestinal tract and cause abscess of the liver. The Shiga bacillus is another cause of dysentery. Typhoid fever and cholera are of course due to their specific bacteria which are generally absorbed with the drinking w ater. Certain intestinal parasites constitute a danger to be reckoned with by acclimatizing strangers. The ordinary cestodes or tape-worms require only a pass- ing mention as their cysticerci can be readily killed by the cooking of the flesh of their intermediate hosts, swine {Taenia solium), cattle {T. saginata) and fish (7\ bolhricephalus). A schistosomum, known as Bilharzia ha-matobia (Schistosomum haematobium), is common in most parts of Africa and was brought home by many British sol- diers from the Boer war. It is introduced by drinking water and possibly through bathing. The adult worm causes no disease but the irritating effects of the eggs upon various mucous surfaces when they are deposited in great number, are most serious. In the intestinal tract the inflammation thus set up causes bloody diarrhea. But the worst, effect is in the urinary tract where these eggs cause hematuria, cystitis, and oc- casionally calculi. They may exist also in the lungs and cause hemoptysis. A most important parasite is the Ankylostonium duodenale or its allied Necator americanus, the "hook- worm." This requires no intermediate host. The eggs when passed with the feces and spread upon the ground under conditions of warmth and moisture, develop rapidly and may in moist earth remain alive for months or even years. If introduced into another person on vegetables or by the dirty fingers of him- self or of a cook, they develop in this new person. Moreover, if a person goes barefooted upon such infected soil the larvoe can penetrate the skin of the foot-sole, pass in the blood-stream to the lungs thence into the trachea thence to the esophagus and so to the stomach. In the duodenum they are prepared to hook themselves to the mucous membrane. From the laceration which they cause, a permanent blood- drain is caused and the patient begins to suffer from progressively increasing anemia which may become as profound as pernicious anemia. Fatty degenera- tion of viscera follows. The patient may have constipation or dysentery, but in either case is always passing the eggs, to be a menace to others. The prophylaxis is in the care of excrement, precautions about vegetables and drinking water, cleanliness of the hands of cooks, and of course always going with the feet shod. Superficial burials must be forbidden. 61 Acclimatization REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Deposition of feces in sea-water destroys eggs and larvae. Plague has been endemic in the Far East for a number of years though the disease has been relatively harmless compared with the great pandemics of "Black Death" which swept Europe in previous centuries. Before a fresh outbreak in any locality it has been noted that an increase of sickness among rats has occurred. Doubtless these animals and also perhaps squirrels serve to propagate the plague bacillus and to infect man. Rats with open ulcers are especially active agents in keeping the disease alive. In this condition fleas may serve to convey the infec- tion from the rats to man. From the end of winter to the beginning of the rainy season is the term of greatest danger (January to June). The destruction of all vermin of whatever size is the chief element of prophylaxis. It will be noted that most of the precautions needed by a European coming into the tropics center about insects and vermin which are the most important carriers to man of the worst tropical diseases. The antityphoid vaccination now so generally practised among large bodies of men in our own country is an especially wise precaution for the immigrant into tropical countries where enteric fever is known to be, as it usually is, prevalent. Beyond the foregoing considerations, the principal factors conducing to acclimatization are those of general hygiene and social environment. Every means should be taken to overcome homesickness. If society is wanting, work must be relied upon to take up the mind. It is said that the workers acclimatize more readily than the idlers in hot countries. Of the various forms of exercise, which is always so important from a hygienic point of view, riding and driving are especially desirable in warm countries. Cool and cold baths daily are of use. The advantages of hydrotherapy are often combined with those of high elevation in the sanatoria which are located in the mountainous districts (where such exist) in many warm countries, and whither the half- acclimated European repairs from time to time with much benefit to paludic, dysenteric, and hepatic affections. Finally, if dysentery obstinately recurs in the high altitude, or if the system does not throw off miasmatic impressions, it is better, after a reason- able time, to abandon the attempt at acclimatization and return to a temperate climate. The ocean voyage will be likely to cause some relief, and after a reconstitution of the bodily powers in the home country, a second attempt at acclimatization may be more successful. Chakles F. Withington. Accommodation and Refraction. — Accommodation is the word used to designate the adjustive power of the eye for distinct vision at different distances: in modern ophthalmology it denotes the active increase in optical power by which the eye changes its adjust- ment from longer to shorter distance--. The existence of an active accommodation, effected through an increase in the convexity of the crystalline lens, was demonstrated by Thomas Young (Philo- sophical Transactions, 1801), but the conclusiveness of his proofs was not generally recognized until fully half a century later. The first actual observation of th<> change in curvature at the anterior surface of the crystalline lens, by Maximilian Langenbeck (1849), was confirmed (1853) by A. Cramer, who, by the employment of more refined methods, demonstrated an associated forward displacement of the anterior lens surface. Cramer's observations were followed closely in time by the wholly independent research of H. Helmholtz (1S55), which definitively estab- lished the fundamental theory of accommodation and opened the way for the exhaustive investigations of Donders, as presented in his monumental work "On the Anomalies of Accommodation and Refrac- 62 tion of the Eye" (1864). Tscherning, who took up the subject anew (1S94, 1895), brought to light impor- tant additional details. The changes in the eye in accommodation consist essentially in (a) a notable increase of curvature in a central area of the anterior surface of the crystalline lens, (6) a much smaller but positively demonstrated increase of curvature in a central area of the poste- rior surface of the crystalline lens, and (c) an increase in the axial thickness of the crystalline lens, measured by the central displacement of its anterior surface; the position of the center of the posterior lens surface remaining unchanged. Accommodation is accompanied by active contrac- tion of the pupil, the effect of which is to stop off all but a comparatively small central portion of the crystalline lens, with exclusion of the much larger equatorial zone from participation in the formation of the retinal image. Both accommodation and the accompanying pupillary contraction are essentially binocular acts, and are sensibly equal in the two eyes. They are, moreover, intimately associated with con- vergence of the visual axes, thereby making it possible to see near objects single, as well as distinctly, with the two eyes. The several adjustments which go to make up the complex act of binocular accommodation are coordi- nated under the control of the third (oculomotor) pair of cranial nerves. Thus the impulse to accommo- date, in order to see a small near object distinctly, evokes not only the needful lenticular changes with contraction of the pupil, in both eyes, but also the correlated action of the exterior muscles of both eyes in convergence for the distance of the object. Con- versely, the impulse to converge, so as to make the two retinal images fall each at the central fovea in its own eye and so prevent confusion from double vision, evokes commensurate exercise of the accommodation with contraction of the pupil, in both eyes. The physiological bond by which accommodation and convergence are coordinated is, however, elastic, within certain limits. Thus the relation of the two adjustments may be altered, for the time being, by looking through concave or convex spectacles, or through divergent or convergent prisms, so as, with unchanged convergence, to force or to relax the accom- modation, or, with unchanged accommodation, to increase or to diminish the convergence of the visual axes. Such experiments are, however, fatiguing, and cannot, as a rule, be long continued without giving rise to a sense of ocular strain, or to headache or other reflex nervous disturbance. Again, accommodation becomes more and more difficult, with advancing age, as a result of progressive induration of the crystalline lens, but is nevertheless maintained, under convergence for a practicable read- ing distance, to an average age of about forty-five years at which the disability of old sight {presbyopia) ordinarily asserts itself. Again, many persons, subjects of anomalies which involve notable alteration of the relation of accommo- dation to convergence, experience no difficulty in near work or perhaps even imagine that they enjoy exceptionally good vision. These are generally cases either of congenital anomaly or of an anomaly of so gradual development as to afford time for a corre- spondingly gradual change in the mutual relation of the two adjustments. The accommodative increase in the optical power of the eye, designated by Donders (1858) as the range of accommoiliilinn, is conveniently estimated in units called dioptries; one dioptric (1 D) denoting the power of a convex lens of one meter focal length, 2 D the power of a lens of one-half meter focal length, etc. The maximum range of accommodation for any eye is attained when the fellow eye is covered or otherwise excluded from participation in the visual act and is free to assume a position of extreme convergence. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES AcooniT lallon and Refraction This maximum range is called the absolute range of accommodation. The range of accommodation for the two eyes together, under convergence for any particular distance, is called the binocular range of accommodation; and the range "over which we have control at a given convergence of the visual lines, [which] represents the degree in which accommodat ion is independent of convergence," is called the relative range of accommodation. The relative range of accommodation varies greatly for different distances. Thus Donders found thai in the case of a young person, of the age of fifteen years it was possible to accommodate with either eye singly up to a distance of 3.69 Paris inches (about 10 cm. = T \ T meter), indicating an absolute range of accommodation of about 10 D. With the two eyes together, it was possible to see distant objects dis- tinctly through concave glasses of any power up to a limit of eleven Paris inches (negative) focal length (about 29.7 cm. =r£, meter), indicating a relative range of accommodation of about 3.37 D under parallelism of the visual axes. Under convergence for a distance of 3.9 Paris inches (about 10.5 cm. = oH meter) it was just possible to accommodate for that distance, but it was also possible to see distinctly, with the two eyes, through convex glasses up to a limit of nine Paris inches (about 24.3 cm. = £i meter focal length, indicating a negative relative range of accommodation of about —4.1 D. Under higher grades of convergence, i.e. for distances less than 3.9 Paris inches (10.5 cm. =^j meter), it was impossible to accommodate with the two eyes for the distance of the point of intersection of the visual axes. At all distances greater than 10.5 centimeters small objects were seen distinctly and single through concave glasses, and also through convex glasses; in other words, the relative range of accommodation was in part positive and in part negative. "This distinction acquires practical importance from the fact that the accommo- dation can be maintained only for a distance at which, in reference to the negative, the positive part of the relative range of accommodation is tolerably great." (Donders.) Fig. 15 shows, in the form of a diagram, a series of measurements of the relative accommodation in the ease cited, as plotted by Donders; the ordinates in- dicating dioptrics of accommodation, and the abscissas the distances of points of intersection of the visual axes, in fractional parts of a meter. By inspection of the diagram it is seen that the positive part of the relative range of accommodation — i.e. the part above and to the left of the diagonal KK — appears only in convergence for distances greater than about rSr meter (10.5 cm.). At a distance of I meter (12.5 cm.) the positive part is about four-tenths as great as the negative; at one-third meter (33.3 cm.) the positive part exceeds the negative in the ratio of about 16 to 10. These observed relations of the positive to the negative part of the relative range of accommodation are in close accord with every-day observation of the working of the accommodation in young persons. Thus a child of say twelve years can ordinarily force his accommodation so as to see minute objects dis- tinctly for a short time at a minimum distance of about 10 centimeters, using about 10 D of accommodation. At a little greater distance, about 12.5 centimeters, using about 8 D of accommodation, he can read for a much longer time, although not, as a rule, without consciousness of effort leading to fatigue. At about 20 centimeters, using about 5 D of accommodation, the accommodation can . often be maintained for hours together in close work, but not without in- curring the risk of ultimate injury to the eyes when reading at so short a distance has become habitual. The limit of ease and safety, for young persons, in long-continued use of the eyes in reading and study, is about 33 centimeters (about thirteen English inches), or perhaps a little less, corresponding to an habitual use of about 3 Dofaccon lation. At this distance the relative range of accommodation Is ample, and the positive part is al about its maximum. The letters r, r„ r„ and p, p„ p, (Fig. 15) indicate the observed absolute, relative, and binocular fait he I and nearest points, respectively, of distinct vi ion. Under parallelism of the visual axes the absolute far point (r) and the binocular far point (r 2 ) fall together al an infinite distance; but there is a positive relati e accommodation of about 3.37 1). Under convergence for a distance of '. meter (10.5 cm.) the relative near point (p,) and the binocular near point (p..) fall • >; r ft, '" P| M j ' , / y / //'. 1 y r, l i l_l_J_JLJ_J.iliii_L±AJ-XX-LJ 1 £ 3 4 5 7 8 9 10 11 12 13 14 15 10 17 18 l'J £' Fig. 15. — Diagram showing the relative range of accommodation for different distances. (After Donders.)* together, but there is a negative relative accommoda- tion of about 4.1 D. Under increased convergence, for distances less than 10.5 centimeters, at which binocular accommodation is no longer possible, the i negative) relative range of accommodation decreases until, under forced convergence for about one- eighteenth meter (about 5.5 cm.), the relative near point (p,) and the relative far point (r,) fall together at the absolute near point (p). Table A. Accommodation t i 2 34567S9 10 11 12 13 1115 1617 1819 20 in dioptries. J Distances in 1 « uiiiitu 1 j i i i i I i J i i \ 00 1 2 3 i 5 u 7 S § ID 11 I: 13 II IB 13 17 Ifl i Q meters. J Table A represents, in parallel series, consecutive dioptries of accommodation and the corresponding distances of the points of intersection of the visual axes in binocular fixation. It will be remarked that the first dioptrie of accommodation covers all distances from infinity to 1 meter; that the second covers a distance, 1-4 =\ meter; the third, £-i=tj meter; the fourth, £-i= T W meter; the tenth, | - T V = ^ meter; etc. Designating the distance of the farthest point (r) of distinct vision for any eye by R, and the distance of the nearest point (p) of distinct vision for the same eye by P, the distance, R — P, increases at a progressively increasing rate as R approaches infinity, and decreases at a progressively decreasing rate for * Fig. 15 has been slightly changed to conform to the metric sys- tem, which has come into general use in ophthalmology since the publication of Donders' work. 63 Accommodation and Refraction REFERENCE HANDBOOK OF THE MEDICAL SCIENCES decreasing values of R. The linear distance R — P, — the region of accommodation of Donders — has a significance wholly distinct from that of the range of accommodation, (p — w) dioptries, as will appear in connection with the study of the Anomalies of Refraction and their correction by spectacles. Refraction, as the word is used in ophthalmology, denotes either the absolute optical power of the eye as determined by the radii of curvature of its several surfaces and the refractive indices of its several media, or the power estimated as deficient or ex- cessive according as the focus of the eye for parallel rays falls behind or in front of the retina. The refraction of the eye as a whole is the sum of consecu- tive refractions, (a) from the air into the cornea, (6) from the cornea into the aqueous humor, (c) from the aqueous humor into the crystalline lens, (d) from layer to layer of the crystalline lens, through a medium of progressively increasing refractive power (index of refraction) from its anterior surface toward its center and of decreasing refractive power from its center to its posterior surface, and (c) from the crys- talline lens into the vitreous humor. Inasmuch as the curvatures of the several refracting surfaces and the indices of refraction of the several transparent media remain constant or nearly constant, after the eye has once attained to its full development, the absolute refraction is practically constant for any particular eye. The principal posterior focus of the eye falls at an average distance estimated as 14. SO millimeters behind its second nodal point (k"), 19. S7 millimeters behind its second principal point (h"), and 2_ > ._':i millimeters behind the anterior surface of the cornea at its center; the last measure representing the distance of the retina from the vertex of the cornea in a normally proportioned eye of average dimensions. Inasmuch as the power (in dioptries) of a compound refractive system is the reciprocal of the distance (in meters or decimal parts of a meter) at which its principal focus falls beyond its second nodal point (k"), the quotient, ^-FTTToZ = 67.29 represents, the U.U14ou optical power of the average human eye, in dioptries.* Measurements of the curvature of the cornea and of the two surfaces of the crystalline lens are found to vary considerably in different persons, and this without giving rise to any related functional disturbance. The explanation is found in a corresponding variation in the size (length of axis) of the eyeball. In a person of large stature all the measurements of the eye are apt to exceed the average; the absolute re- fraction of the larger eye being someu hat less and the size of the inverted retinal image somewhat greater, than in the case of a smaller eye. A larger eye is therefore, ceteris paribus, of somewhat greater visual acuity than a smaller eye, just as a photo- graphic lens of longer focus, in a larger camera, gives * By making permissible small changes in the computed dis- tance of the second principal point (A") and of the second nodal point (fc") from the retina, Donders showed that it is possible to reduce the several refractions in the eye to an equivalent single refraction at a convex spherical surface of 5 nun. radius of curva- ture, bounding a refractive medium of g = 1.3 index. In this "reduced" eye the focus for parallel rays falls 20 mm. behind the single principal point (p) at the vertex of the spherical surface, and 15 mm. behind the single nodal point (k) at its center of curvature. The power of the reduced eye, n „, ^ =66.6 dioptries, and the 0.01 o ratio of the size of a distant object to that of its inverted image, — , differ negligibly from those based on the measurement, used in the "schematic" eye of Listing as revised by Helmhobz. The easily remembered numbers, 5, 15, 20, or their ratios, 1 : .'! : 1, may therefore be used without appreciable error in numerical calculations, ami in geometrical constructions illustrating fundamental problems ifi physiological optics. a larger and more perfect picture than a lens of shorter focus, in a smaller camera. The estimation of the absolute refraction in a particular eye involves objective measurements too refined to be attempted in clinical work, and also of no practical significance unless supplemented by a tin ire accurate measurement of the length of the eye- ball than is possible in the living subject. On the other hand, estimates in terms of refractive defi- ciency or excess are readily made by testing with convex or concave trial-glasses, and are also directly available in prescribing spectacles. We have, therefore, to recognize, first of all, a standard of correct proportion, emmetropia, E (from epperpos, proportionate, and Sxp, eye), in which a sharply defined image of a distant object is formed on the retina without the exercise of any part of the accommodation, so that the entire range of accom- modation is available to meet the requirements of distinct vision for near objects. The region of accom- modation includes, therefore, all distances from infinity to a near point (p) which is near enough to the eye to satisfy exacting requirements in close work. The definition of emmetropia as correct proportion implies the negative concept of incorrect proportion, ametropia (from dpiTpos, disproportionate, and &ii, eye), in which the principal focus of the eye falls elsewhere than at the distance of the retina. Ame- tropia occurs under two opposite types, according as the retina lies in front of or behind the principal focus. Hypermetropia, H (from v-(p, over, phpov, meas- ure, and &(,'■, eye), is the condition in which the prin- cipal focus falls behind the retina. A hypermetrope whose range of accommodation is in excess of that required to advance the focus for parallel rays to the actual position of the retina, is able, through the exercise of some part of his accommodation, to see clearly at a distance. A part only of the range of accommodation is then available for near vision and, by reason of the near point falling too far from the eye, the region of accommodation is commensurately curtailed. In the higher grades of hypermetropia the normal range of accommodation is often insuffi- cient for distinct vision even at a distance; in the lower grades it is generally possible to read, but pro- longed effort is apt to give rise to a feeling of strain or fatigue, with blurring or "running together" of the print. With the progressive recession of the near point incident to advancing age, these (asthenopic) symptoms and disabilities give place to those of pre- mature old sight (presbyopia), and ultimately to indistinctness of vision at all distances. In typical hj-permetropia the disproportion is the expression of actual deficiency in the length of the anteroposterior diameter of the eyeball. The relative nearness of the retina to the second nodal point of the eye, and the fact that hypermetropia is hereditary, suggest reversion to structural conditions found in the lower mammalia. The crucial test of hyperme- tropia is the ability to see distinctly at a distance through convex glasses; its measure, in dioptrics, is the strongest convex lens through which vision at a distance is unimpaired. (See Hypermetropia.) Myopia, M (puunrlct, puio-laois, pou*,'', from piu), to close or contract, and &ib, eye), so named by early writers from the habit of contracting the opening of the eyelids in looking at distant objects, is the exact opposite of hypermetropia in that the principal focus of the eye falls in front of the retina. A myope sees indistinctly at long distances, but is able to accom- modate for a distance a little less than that of the near point in emmetropia. The region of accom- modation is greatly curtailed through the approach of the far point to the eye, with unimportant com- pensation in the approach of the near point; in very high grades of myopia the region of accommodation i~ reduced to insignificance. In myopia of low grade the disability of old sight (presbyopia) first asserts 64 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Accommodation and Refraction itself at a later period of life than in emmetropia; in the higher grades, in which the far point (r) lies well within the ordinary reading distance, presbyopia, in the ordinary acceptation of the word, is an Impossibility. In typical myopia the disproportion is the expres- sion of axial elongation in a pathologically distended eyeball. Myopia generally appears in childhood, and increases progressively during the period of school life; the increase in grade being in direct relation to the habitual use of the eyes at too short a working distance. Unlike hypermetropia, myopia is the visual expression of disease which, in later life, may progress even to loss of sight. The test of myopia is the inability to see distant objects distinctly except through concave glasses; its measure, in dioptries, is the weakest concave lens which brings distant vision up to the same relative acuteness as at distances within that of the far point. (See Myopia.) The positions of the far point (r) and the near point (p) are measured from the first nodal point (A-') which is situated about 6.95 millimeters behind the vertex of the cornea. Representing these distances by R and P, respectively, the range of accommodation, in dioptrics, by A, and the degree of myopia or of hyper- metropia, in dioptries, by M or by — H, we have: In emmetropia, in myopia, in hypermetropia. R =infinity, P = meter; R =,, meter, M P = 1 A + M meter; 1 R = — ■' meter, It P = -7 — ;. meter. A — H From a comparison of these equations it will be seen how, for the same range of accommodation, the region of accommodation is most extensive in emmetropia. In myopia the region of accommodation is greatly curtailed through the approach of the far point (r), with unimportant compensation in the approach of the near point (/>). In hypermetropia of low grade, in which only a part of the range of accommodation is available in near vision, the region of accommoda- tion is curtailed through the recession of the near point (p) from the eye, the visual far point falling, as in emmetropia, at infinity. When H is so large, or A so small, that A is less than H, the entire range of accommodation becomes negative, and distinct vision is impossible at any distance. When a concave spectacle lens of an effective power equivalent to — M dioptries is worn in front of a myopic eye, or a convex lens of +H effective power is worn in front of a hypermetropic eye, the corrected linear values in myopia, in hypermetropia, R = P = 1 = infinity, M - M 1 1 -j .-,- — ., ■= , meter A + M - M A R =g-— g = p=infinity, P = A-H + H = A meter; are the same as in emmetropia; the far point (r) falling at infinity, and the near point (p) at a dis- tance expressed by the reciprocal of the range of accommodation. We have thus far considered myopia and hyper- metropia from the standpoint of vision with one eye, ignoring, for the moment, the complications which grow out of the participation of the two eyes in binocular vision. In brief, it may be said that in order to see an object single and distinctly with the two eyes together, the eyes must be directed each to the same point, and this point must be a point for whose distance each eye is accommodated. This close interrelation of accommodation and convergence gives rise to important complications both in myopia and in hypermetropia. In myopia, there is com- paratively little occasion for the exercise of the accom- modation, whereas the angle of convergence for the distance of most distinct near vision is never less and may be notably greater than in emmetropia. This, normal or excessive, convergence may in turn evoke accommodation for a shorter distance, thereby neces- sitating increased convergence. Thus through vicious interaction of the two adjustments the grade of myopia may appear to be greater than it really is, and, under habitual use of the eyes at too short a distance, the distention of the eyeballs may increase to the point of imminent danger. On the other hand, a myope may faL into the habit ot relaxing the accommodation to the degree requisite for distinct vision at or near his far point, in which case the at- tendant relaxation of the convergence may lead to relative insufficiency of the recti interni muscles (muscular asthenopia); or the effort to maintain binocular vision may be abandoned, and actual muscular insufficiency (crossed double vision, or divergent strabismus) ensue. In hypermetropia the eyes accommodate even in distant vision, and must accommodate more strongly than in emmetropia in order to see near objects distinctly. Accordingly, in hypermetropia one of two complications may arise: either convergence may be maintained for the distance of the object, in which case the over-burdened accommodation may prove unequal to the demand made on it in sustained near work (accommodative asthenopia), or the accommodation may be maintained under excessive convergence, with suppression of binocular vision, which may be the forerunner of convergent strabismus. The complications growing out of faulty relation between accommodation and convergence have been formulated by Donders in the pregnant antithesis: Hypermetropia causes accommodative asthenopia, to be actively overcome by strabismus convergens. Myopia leads to muscular asthenopia, passively yielding to strabismus divergens. Astigmatism, As (from a- privative and ozlyiia. a point), is a very common structural anomaly in which the power of the eye is unequal in different meridians. This inequality is greatest in two ocular meridians at right angles to each other, called the principal meridians. An astigmatic eye may be emmetropic in one of its principal meridians, in which case it is either myopic or hypermetropic in the other; or it may be myopic or hypermetropic in both meridians; or it may be myopic in one of its principal meridians and hypermetropic in the other. In binocular hypermetropic astigmatism the disabilities are, in general, those of hypermetropia; and in binocular myopic astigmatism are, in general, those of myopia. As the acuity of vision is below the normal at all distances, an astigmatic person is apt to fall into the habit of reading at too short a distance, and may thus awaken or revive a pre-existing tendency to myopia. The correction of regular astigmatism together with any accompanying ametropia, by wearing appro- priate cylindrical, spherico-cylindrical, or toric spec- tacles, both improves vision at all distances and mini- mizes the incidental disabilities and dangers (see Astigmatism.) Anisometropia (from Jywos, unequal, fihpov, meas- ure, and Slip, eye) — signifying a difference in the meas- urements of the two eyes — is the word commonly used Vol. I.— 5 65 Accommodation and ltd' raction REFERENCE HANDBOOK OF THE MEDICAL SCIENCES to denote inequality of refraction; as when: (a) one eye is emmetropic and the other eye is either hyper- metropic or myopic; (6) the two eyes are unequally hypermetropic or myopic; or (c) one eye is hyper- metropic and the other myopic.* As the increase of power in accommodation is sensibly equal in the two eyes, the refractive inequality is virtually the same in vision at all distances; s<. tiiat, when one eye is accommodated for any particular distance, the fellow eye accommodates for some other distance and the image formed on its retina is imperfectly denned. In cases of small or medium difference in refraction the difference in definition may pass un- noticed, and cases of greater difference are often vaguely described as "something wrong with one eye." In uncomplicated anisometropia both images are commonly utilized in binocular vision, with more or less perfect conservation of the faculty of recognizing differences in distance and the forms of solid bodies (stereoscopic vision). An anisometrope with one emmetropic or moderately hypermetropic eye of approximately normal acuity of vision will generally use that eye in distant vision, and also in reading unless the other eye happens to be myopic; in either case he may remain unconscious of the fact that he does not see distinctly with both eyes at the same time until, perhaps, an intercurrent disabling of the eye in habitual use for a particular distance reveals a previously unrecognized anomaly in the fellow eye. In hypermetropia of unequal grade in the two eyes, the disabilities and complications are ordinarily the same as in binocular hypermetropia of a grade equal to that in the less hypermetropic eye (see Hyperme- tropic!). In myopia of unequal grade in the two eyes the more important complications are those of binoc- ular myopia of a grade equal to that in the more myopic eye (see Myopia). The indications, and also the opportunity, for prescribing glasses of unequal power, with a view to equalizing the adjustments of the two eyes in binocular vision, vary notably for different cases. An aniso- metrope who sees clearly at a distance, and also reads ordinary print fluently, seldom thinks of glasses, and when one eye is myopic he may be able to read without glasses far beyond the age at which Eresbyopia ordinarily asserts itself as a disability. In ypermetropia of unequal grade in the two eyes, an increasingly disabling asthenopia, passing gradually to presbyopic vision, may suggest the purchase of a pair of convex glasses which afford needed help in reading and which may be found to be helpful also in seeing at a distance. In myopia of unequal grade in the two eyes a pair of concave glasses, which ap- proximately correct the less myopic eye for distance and partially correct the fellow eye, may be accepted as satisfying recognized needs, and when the uncor- rected part of the myopia in the more myopic eye is rather large the disability of presbyopic vision, even with the concave glasses, may be long or perhaps indefinitely deferred. In any of these cases an ani-ometrope may see cause only for self-congratula- tion in his enjoyment of special immunities, and may give little heed to less obvious disabilities or to in- sidious changes in vision. The complications which may make it imperative to prescribe glasses of unequal power occur oftenest in myopia of one eye or in myopia of unequal grade in the two eyes. In both of these cases the habitual relaxation of the accommodation, inhibiting free exercise of the convergence, may lead to relative insufficiency of the recti interni muscles (muscular asthenopia), or absolute insufficiency of the recti interni (crossed double vision, or divergent strabis- mus). On the other hand, habitual convergence for a short reading distance may evoke accommoda- * The name antimetropin has been proposed for the particular form of anisometropia in which one eye is hypermetropic and the other myopic. 66 tion for a shorter distance, at which binocular vision is possible only under increased convergence, and the pathological processes which find expression in pro- gressive distention of the eyeball may take on renewed and perhaps dangerous activity. In any one of these conditions the wearing of a concave glass chosen with reference to this grade of myopia in the eye habitually used in reading may be indicated, but the effect of a second concave glass of the same power would ordinarily be detrimental by creating a possibly disabling artificial hypermetropia of the fellow eye. In general, the treatment of a case of anisometropia by glasses involves (a) the determination of the acuteness of vision and of the refraction, including astigmatism, in both eyes; (6) an estimate of the range of accommodation in both eyes; (c) the detec- tion and approximate estimation of any actual or latent error in the direction of the visual axes in distant or in near vision; and (d) such provisional or final correction of both eyes as may be found to be most helpful in binocular vision. In many cases the best results are attained by wearing glasses of unequal power corresponding to the difference in refraction; in other cases a partial equalization of the refraction may be preferred in the beginning, and a full equal- ization accepted a few weeks or months later. In still other cases, in which binocular vision has perhaps never been established or has been long abandoned, attempts at binocular correction may be rejected as of no avail, or as reviving disabilities from w'hich the patient has found relief through the habitual exclu- sion of one eye from participation in the visual act. Aphakia (from a- privative, and ai<6s, lens, a lentil) is the condition in which the crystalline lens is either wholly wanting or is so displaced that it no longer lies in the axis of the eyeball. As. a result of loss of the crystalline lens the first and second prin- cipal points of the eye fall together in a single princi- pal point at the vertex of the cornea, and the first and second nodal points fall together in a single nodal point (optical center) at its center of curvature. Computing the principal focal length from the aver- age radius of curvature of the cornea at its center (8 mm.) and an assumed common index of refraction for the cornea and the aqueous and vitre- ous humors (^- = 1.337) , the principal focus of the aphakial eye falls 31.7 millimeters behind the vertex of the cornea, and 23.7 millimeters behind the (single) nodal point at its center of curvature. The absolute power ( „.,„-. =42.2 dioptries) of the aphakial eye is therefore about twenty-five dioptries less than thai of the average unmutilated eye. As the apha- kial eye has also suffered a total loss of accommoda- tion, it requires a strong convex glass in distant vision and a still stronger convex glass in reading. The effective power of a convex spectacle lens in- creases, however, for every increase in its distance from the (first) nodal point of the eye, so that a glass of ten to twelve dioptries worn about 15 millimeters in front of the cornea of an aphakial eye ordinarily suffices to advance its focus for parallel rays to the actual position of the retina. The convex glass also enlarges the retinal image by advancing the (second) nodal point (of the corrected eye) to a position farther from the retina than in the emmetropic eye. A partial adjustment for the near, with additional enlargement of the retinal image, may be obtained by wearing the convex glass still farther from the eye, but as such increase in distance is limited practically to the length of the nose it is generally too small to afford the additional help required in reading. In the case of aphakia in a previously hypermetropic eye stronger convex glasses, and in the case of aphakia in a previously myopic eye weaker convex glasses, are required for distance and in reading. In a case of pre-existent myopia of exceptionally high grade, REFERENCE HANDBOOK OF THE MEDICAL S( 1KN< i;s \. commoda Hon and Kef r.i. 1 1. .11 with excessive elongation of the eyeball, much weaker convex glasses suffice; a fact which Ion;; ago SUg- ge ted tin- surgical removal of the crystalline lens in cases of myopia of so high a grade as to constitute extreme and otherwise irremediable disability (see M>i<>pia). In corrected aphakia of one eye the retinal image is notably larger than in the fellow eye, but even with this drawback the correction is gener- ally of value by helping to keep the aphakia! eye in use in binocular vision. An uncorrected aphakial eye may, however, continue to take part in binocular vision, and it is also an important safeguard against the danger of colliding with a moving object, such as a horse or vehicle, approaching from the side corre- sponding to the affected eye. A considerable grade el astigmatism is frequently present in aphakia, and may be due either to original asymmetry of the cornea or to acquired asymmetry following the healing of a corneal wound or of the corneal incision in the operation for the extraction of cataract. Low grades of astigmatism are often overcome by looking obliquely through the strong convex glasses worn to correct the aphakia; higher grades may require correction by a special lens. (See Astigmatism.) Disorders of accommodation- occur as a result either of progressive induration of the crystalline lens, or of disordered innervation. The crystalline lens, which in a young child is of the consistency of a firm jelly, becomes gradually harder from year to year. With increasing indura- tion, the range of accommodation decreases until, after middle life, it is no longer possible for the emmetropic eye to accommodate for the ordinary reading distance. (See Presbyopia.) The age at which the failure of accommodation is recognized a- a disability varies according to the refractive con- dition. A myope whose farthest point (r) of distinct vision lies well within a reading distance of thirty- three centimeters (thirteen inches) never becomes presbyopic in the sense of being unable to read with- out the aid of convex glasses; but whereas in youth he reads easily with the concave glasses which correct his myopia, he is compelled, with advancing age, either to lay aside his glasses in reading or to exchange them for weaker concave glasses than those through which he sees well at a distance. In hypermetropia the loss of accommodation shows itself by an early recession of the near point (p), so that help is sought from convex glasses, perhaps long before the usual age of from forty to forty-five years. The young hypermetrope, wearing convex glasses which correct his hypermetropia, sees distinctly at all distances, anil it is only at the age of about forty-five years that he finds himself compelled to make use of stronger reading glasses. In no condition of the refraction does a presbyope see clearly at a distance and read easily with the same glasses. Either he is an emme- trope, in which case he requires convex glasses for reading, but sees imperfectly through them at a distance; or he is a myope, and so requires concave glasses for distance, and weaker concave glasses, or no glasses at all, or possibly weak convex glasses, in reading; or he is a hypermetrope, and so sees dis- tinctly at a distance with neutralizing convex glasses, but requires stronger convex glasses for reading. Paralysis or paresis of accommodation from defective innervation may be the result of an affection limited to the terminal ramifications of the ciliary nerves, or involving the oculomotor nerve in any part of its course or at its origin. It is generally accompanied by dilatation and loss of mobility of the pupil, and in many cases also by paralysis or paresis of one or more of the muscles supplied by the oculomotor nerve, namely, the levator palpebral superioris, the rectus superior, the rectus inferior, the rectus internus, and the obliquus inferior. A typical example of paralysis of accommodation dependent on suppression of the function of the terminal branches of the ciliary nerves is that which follows the instillation of a mydriatic solution into ilie conjunctival sac. Within fifteen minutes after the instillation of a drop of a solution of atropine sul- phate of a strength of one per cent. (1 :100), tne pupil begins to dilate, and within half an hour the dilata- tion reaches its maximum; the pupil no longer con- tracting under the stimul ong light, closely following the dilatation of the pupil, the ileal point i/ii recedes from the eye, ami the paralysis of accom- i lation is generally complete at the end of about an hour and a half. The dilatation of the pupil and the paralysis of accommodation continue without sensible change for about two days, after which both begin to pass away, the former very gradually, the latter more rapidly for two or three days and after- ward more slowly, until at the end of ten or twelve days the effect of the drug disappears altogether. A very weak solution of atropine, say of a strength of one one-hundredth of one per cent. (1:10,000), dilates the pupil in the course of an hour and a half or two hours, but without rendering it immovable under the influence of strong light, and without sensibly affecting the accommodation. Under full action of atropine the near point (/>) recedes from the eye until it comes to coincide with the far point (r). The visual disturbance varies greatly according to the refractive condition of the eye. In emmetropia distant vision remains clear, but it is impossible to read without convex glasses; in hypermetropia vision becomes indistinct for distance, and still more so for the near; in myopia of a rather high grade there may be no trouble in reading without glasses and the recession of the near point may pass unno- ticed. In the case of a hypermetrope or a myope wearing neutralizing glasses the visual disturbance is the same as in emmetropia. Several plants, of the natural family Solanacece, yield alkaloids whose action is nearly identical with that of atropine. Hom- atropine, a derivative of atropine or of hyosciamine, is less lasting in its effect, and is used to paralyze the accommodation in measuring errors of refraction. Cocaine, the active alkaloid of Erythroxylon coca, and euphthalmin hydrochlorate, a synthetic product used in ophthalmic practice, dilate the pupil without sensibly affecting the accommodation. Concussion of the eyeball is sometimes followed by more or less persistent dilatation of the pupil and loss of accommodation, without demonstrable gross ocular lesion. Paresis of accommodation, oftenest without marked dilatation or loss of mobility of the pupils,* is a frequent complication of diphtheria. It appears late in the disease, after recovery from the throat affection, and is generally accompanied by paresis of the faucial muscles giving rise to characteristic alteration of speech with difficulty in swallowing solid food and regurgitation of liquids through the nose. One or more of the external muscles of the eyeball may also be affected, and cases of true convergent st rabismus have been observed as a result of the exces- sive effort to accommodate in the weakened condition of the accommodation. The paretic symptoms simu- late those of overloaded accommodation in hyperme- tropia, and convex glasses are similarly helpful in reading. The instillation of a drop of a weak solu- tion of pilocarpine, several times in the course of the day, may also be helpful. Paralysis of accommodation with dilatation of the pupil (ophthalmoplegia interna) may be the only symptom of a circumscribed cerebral lesion. Oftener * Donders, who was the first to study the disturbance of vision in diphtheria, found dilatation with sluggishness of the pupils in the cases observed by him (1S60) at the time of a grave epidemic in Holland. Binocular paresis of accommodation unaccom- panied by dilatation of the pupils is now generally regarded as evidence of diphtheritic intoxication. 67 Accommodation and Refraction REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the paralysis includes one or more of the muscles supplied by the third nerve, or it may extend to the fourth nerve (trochlearis) and to the sixth nerve (abdu- cens), with resultant complete immobility of the eyeball (ophthalmoplegia externa). An overdose of one of the more active mydriatic drugs (belladonna, stramonium, hyoscyamus, etc.) is followed by wade dilatation of the pupils and paraly- sis of accommodation. With the elimination of the toxic agent the ocular symptoms disappear. Spasm of accommodation, with spasmodic contrac- tion of the pupil, has been studied almost exclusively as induced by Calabar bean {Physostigma venenosum). The instillation of one-fourth minim of a one-half per cent, solution of eserine (physostigmine) into the con- junctival sac is followed after five to ten minutes by spasmodic "twitching," with beginning contrac- tion of the pupil and displacement of the region of accommodation towards the eye. In the course of the next half-hour the pupil is reduced to a diameter of less than two millimeters, with advancement of the farthest point of distinct vision indicating an increase in refraction equal to about two-thirds of the absolute range of accommodation.* Recession of the far point follows, and is complete, in distant fixation, after a little more than an hour, but excessive accom- modation, in convergence for the near, persists for twelve hours or longer; near objects, seen under consciously relaxed accommodation, appearing as if farther away, and therefore larger, than under normal conditions (macropsia).t The instillation of eserine in larger quantity or in a stronger solution is followed by more intense and painful spasm, which may continue for several hours; the persistent instillation of a strong solution of eser- ine, in animals, is attended by general toxic manifes- tations ending in death. Pilocarpine (the active alkaloid of Pilocarpus jaborandi) acts much more mildly than eserine, but is, nevertheless, an efficient myotic and stimulant of the accommodation. Extreme contraction with immobility of the pupils is a typical symptom of poisoning by opium, and v. Graefe showed (1S61) that the hypodermic injec- tion of morphine, in therapeutic doses, is followed also by a temporary increase in refraction due to stimula- tion of the accommodation. In the earlier studies of the general toxic action of Calabar bean, in animals, strong contraction of the pupil was noted as a con- stant condition, and there can be little doubt that the myosis is accompanied by acute spasm of accommoda- tion. The hypodermic injection of pilocarpine in maximum therapeutic doses is not followed either by contraction of the pupils or by stimulation of the accommodation. Stimulation of the ophthalmic division of the fifth nerve (trigeminus), in animals, causes contraction of thr pupil, and the same (reflex) symptom, accompan- ied by photophobia, is generally present in cases of painful abrasion, phlyctenula, etc., of the cornea. Spasm of accommodation, with strongly myopic vision and a sluggish but not conspicuously contracted pupil, has been known to persist after apparently perfect recovery from a superficial injury of the cornea. Tension of accommodation is a permanent condi- tion in young hypermetropes, who necessarily make use of some part of their accommodation in distant vision; subjective tests, made with convex glasses, showing a lower grade of hypermetropia than is revealed after paralyzing the accommodation by * As measured by Donders. The advancement of the far point i I. 3 in patients wi th restricted than with large range of accommo- dation. The distance of the advanced far point from the eye is greater in hypermetropia, and less in myopia, than in emmetropia. t Conversely, as remarked by Donders (1851), in artificially induced paresis of accommodation, near objects, viewed under consciously increased accommodation, appear smaller than under normal conditions (micropsia). atropine. This state of unconscious tension may be maintained for many years in a person with normal acuteness of vision and ample range of accommodation, his hypermetropia first asserting itself as a recognized disability under the aspect of premature old sight (presbyopia). Tension of accommodation simulating myopia, may be induced in a young person by excessive use of the eyes in near work. Enforced study or per- sistent reading in a bad light, prolonged strain in fine needlework or in mechanical drawing, and subnormal acuity of vision in which compensation for imperfect definition is sought by shortening the reading or working distance, are among the more obvious excit- ing causes. The habitual use of the eyes at too short a distance under excessive convergence, inciting in turn to increased accommodation and convergence, is a principal initial and continuing factor in the development and progressive increase of myopia, Under atropine the acquired tension of accommodation disappears; and the correction of any existing ame- tropia, or of an astigmatism revealed by the shadow- test or by the opthalmometer and verified by sub- jective tests, may be all that is needed to reestablish normal conditions. Spasm of accommodation in near work, yielding promptly to atropine but recurring with the passing of the mydriasis, was observed by Donders in three cases; all relieved by atropine used, at intervals of a few days, for several months. Such cases are infre- quent, but probably not as rare as commonly supposed. John Green. Accouchement force. — See Labor, Induction of. Acephalus. — See Teratology. Aceta. — Aceta, or vinegars, are liquid preparations made by treating vegetable drugs or their active prin- ciples, with dilute acetic acid. Vinegar is no longer used as a menstruum, it place being taken by dilute acetic acid. There are only two aceta official in the U. S. P. of 1900; they are of uniform strength, ten per cent. The B. P. contains three aceta and the N. F., three. The official (U. S. P.) aceta are acetum opii (dose rn viii.) and acetum scillre (dose nx x.-xxx.). R. J. E. Scott. Acetal. — Diethylaldehyde, ethylidene -diethylic ether, CH 3 .CH(OC 2 H 5 ) 2 ; a substance produced by the imperfect oxidation of alcohol, distilled from a mixture of the latter with manganese dioxide, sulphuric acid, and water. It is a colorless volatile liquid of an agreeable odor and rather sharp but not unpleasant taste, leaving a nutty after-flavor. It is soluble in eighteen parts of water at 77° F., somewhat less at a lower temperature, and freely in alcohol and ether. Acetal possesses sedative and mildly hypnotic properties. It may be given for the relief of headache and nervous excitement and as an hypnotic in mild degrees of insomnia, especially in those cases in which the early part of the night is wakeful. The dose is from 1 to 3 fluidrams (4.0-12.0) in emulsion with acacia flavored with orange-flower water. T. L. S. Acetaminol. — Para-acetamidobenzoyl-eugenol ; oc- curs in the form of a whitish crystalline powder, soluble in alcohol, but very slightly in water. It possesses antiseptic and mildly hypnotic properties, and has been employed as an intestinal antiseptic in doses of five to fifteen grains (0.3-1.0). T. L. S. Acetanilide. — Acetanilidum (U. S. P.). Phenyl- acetamide, antifebrin, C„N 5 NH.CH 3 CO. This is one of the earliest of the antipyretic and analgesic syn- thetic preparations, introduced as a remedy by Kahn and Hoff in Germany in 1SS6, though first prepared by Gerhard in 1852. It is a monacetyl derivative of ani- line, prepared by the action of glacial acetic acid on ani- line, occurring as a white odorless crystalline powder, or in minute shining scales, having a slightly burning 68 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ArHIc KtliiT taste, soluble in 200 parts of water, in 4.2 parts of 90 per cent, alcohol, in IS parts of ether, and freely soluble in chloroform. Acetanilide is antipyretic, analgesic, and sedative, and is in large doses a cardiac and blood poison. Its first employment was as an antipyretic, but it is seldom so used now owing to its depressing effect. As an analgesic it is still largely used, being given to relieve headache, intercostal and other formse of neu- ralgia, and to still the pains of tabetic crises. As an analgesic it is one of the most powerful of the synthetic drugs, but at the same time one of the most dangerous, and should therefore be used with extreme caution. It acts upon the hemoglobin of the blood, reducing it to methemoglobin and so affecting its oxygen-carrying function and causing cyanosis; it depresses the action of the heart and causes excessive sweating and general debility, and when taken con- tinuously for some time tends to establish a habit. The dose as an anodyne is from one to three grains (0.00-0.2) ; as an antipyretic, two to four grains (0.13-0.25). It possesses antiseptic properties and may be used as a dusting powder to wounds, chan- eroidal and other ulcers, and is also used as an errhine in the treatment of epistaxis. In poisoning from an overdose, stimulants, strych- nine, and atropine should be exhibited, and heat should be applied to the extremities. Strong coffee may be of service and bicarbonate of sodium in large doses has been recommended. Acetanilide is largely employed as the active agent in many of the much advertised headache powders and a number of cases of acute poisoning from its indiscriminate employment by the laity have been recorded, as also cases of habituation from its long continued use. For this reason it has been urged that it be dropped from the Pharmacopoeia, but it is doubt- ful whether such action would diminish its use by the laity, and its really great service as an anodyne in severe pain, such as that of tabes, gives it a rank as one of the most valuable drugs of its class. T. L. S. Acetic Acid.— Acetic acid, CH,.COOH, the well- known acid of vinegar, is a liquid at ordinary tem- peratures, and miscible in all proportions with water. Mixtures of the acid and water in different proportions constitute the different grades of the acid in commerce. Strong acetic acid is caustic, largely through its prop- erty of dissolving the formed material of the connective tissues to a pultaceous translucent substance. Be- ing caustic, it is of course irritant, and swallowed in concentrated condition operates as a corrosive poison, the effects and symptoms being substantially the same as in corrosion by the strong mineral acids. But few cases of death have been recorded. The treatment is similar to that to be employed in case of poisoning by a mineral acid. In non-corrosive strength of solution (five or six per cent., the equivalent of vinegar), acetic acid produces the usual local effects of the sour acids — exciting the flow of saliva and tending to oppose sour fermentation of the food — and is also distinctly astrin- gent. Inhaled the fumes are reviving in faintness and may relieve headache. Acetic acid has many uses in pharmacy. It has been urged that the Pharmacopoeia should substitute acetic acid largely for alcohol as a menstruum for the preparation of extracts; and it has even been proposed that this class of extracts shall bear the special name "Acetracts." In medicine the strong acid may be employed as a caustic, as to warts or cancers, and the weak acid used to make refreshing acid draughts in fever, or cooling lotions in inflammatory skin affections. Acetic acid is official in the U. S. Pharmacopoeia in three forms: Acidum Aceticum Glaciate, Glacial Acetic Add. — This is defined to be "a liquid containing not less than ninety- nine per cent., by weight, of absolute acetic acid (CH,. COOH =59.58), and not more than one per cent, of water." It is "a clear, colorless liquid, of a strong, vinegar-like odor, and a very pungent arid ta te. At a temperature somewhat below 15° C. (.59° F.), the acid becomes a crystalline solid. At 1 17° to 1 ls J C. (242.0° to 211.1 " I'.j it boils, evolving inflammable vapors." (U S. P.) This grade of the acid is for pharinaeeul ieal uses. Acidum Aceticum, Acetic Acid. — The grade of acid thus simply named is a "liquid composed of not less than thirty-six per cent., by weight, of absolute acetic acid and about sixty-four per cent, of water, obtained by the oxidation of ethyl alcohol or by the destructive distillation of wood." It is "a clear, colorless liquid, having a strong, vinegar- like odor, a purely acid taste, and a strongly acid reaction. Specific gravity, about 1.04.5 at 25° C. (77° F.). Miscible with water or alcohol in all proportions. When heated, the acid is volatil- ized without leaving a residue" (U. S. P.). This is the acid that results from the purification of the crude acid — mult pyroligneous acid, so called — obtained by the destructive distillation of wood. This is sharply irritant and even mildly caustic. Dangerous symp- toms have resulted from swallowing it, undiluted, in quantity of two or three ounces. The acid maj' be used as a mild caustic, but its principal uses under its own form are pharmaceutical. Acidum Aceticum Dilutum, Diluted Acetic Acid. — It should contain not less than six per cent., bv weight, of absolute acetic acid (CTI 3 .COOH =59.58), and about ninety-four per cent, of water. Specific gravity, about 1.009 at 25° C. (77° F. ) (U. S. P.) This diluted acid is of the strength of the best qualities of vinegar, and is better than vinegar for all the pur- poses of the same, medicinal or dietetic. Squibb says: " If one part of alcohol be added to about two hundred and fifty-six parts of this diluted acetic acid — that is, about half a fluidounce to the gallon — and the mixture be set aside for a few weeks (the longer the better), enough acetic ether is generated to give it the full, clean aroma of fine vinegar, and then for table use it is very far superior to any vinegar made in the ordinary way by fermenting cider." Diluted acetic acid is the most convenient grade of the acid for medicinal use, and has also, in the U. S. Pharmacopoeia, superseded vinegar for pharmaceuti- cal purposes. For an acid draught a five-per-cent. addition to water is appropriate, and for a lotion a twenty-five-per-cent. addition. The popular notion that the habitual use of vinegar tends to deterioration of nutrition and health is certainly not true of a moderate indulgence, if indeed it be true at all. Edward Curtis. R. J. E. Scott. Acetic Ether. — Under the title Mfher Aceticus, Acetic Ether, the U. S. Pharmacopoeia makes official a preparation consisting of the ethereal salt, ethyl acetate (about ninety per cent., by weight), with a little contaminating alcohol and water, Acetic ether is described as "a transparent, colorless liquid, of a fragrant, and refreshing, slightly acetous odor, and a peculiar acetous and burning taste. Specific gravity, 0.883 to 0.885 at 25° C. (77° F.). Boiling-point, about 72° C (161.0° F.). Soluble in about seven parts of water at 25° C. (77° F.) ; miscible in all proportions with alcohol, ether, and the fixed and volatile oils. Acetic ether is readilj r volatilized, even at a low temperature. It is inflammable, burning with a yellowish flame and an acetous odor" (TJ. S. P.). Acetic ether should be kept in well stoppered bottles and away from lights or fire. The effects of acetic ether upon the animal economy are similar, in a general way, to those of common ether, the most important point of difference being that acetic ether is the slower in operation. For this reason this ether is not available as a surgical an- 69 Acetic Ether REFERENCE HANDBOOK OF THE MEDICAL SCIENCES esthetic; but, on the other hand, by reason of its agreeable odor, it makes an excellent and grateful cardiac stimulant, antispasmodic, and carminative, taken internally. Used externally, it may serve to mask disagreeable odors. It may be given internally, in quantities ranging from fifteen to thirty drops, well diluted with water or with some medicinal prepa- ration, to which the ether is added as an adjuvant or corrigent. R. J. E. Scott. Acetone. — Acetone, CH,.CO.CH„ dimethyl ketone, is a colorless limpid, and inflammable liquid of pungent quality, miscible in all proportions with water, alcohol, and ether. Its effects upon the animal system are, doubtless, of the general nature of those of the volatile alcohols and ethers, but the substance has never been systematically employed as a medicine. It is used for chemical purposes in the manufacture of chloroform, and as a solvent for fats and resins. It occurs normally, in small amounts, as an ingre- dient of blood, urine, etc. R. J. E. Scott. Acetonuria. Definition. — The presence in the urine of a pathological quantity of acetone, CO(CH 3 ) 2 . Historical. — Petters in 1S57 discovered acetone in the urine of a patient suffering from diabetic coma, and three years later Kaulich demonstrated its occurrence in ordinary cases of diabetes and added a clinical picture of the condition known as acetonemia. Kussmaul in 1874, writing on diabetic coma, first threw doubt on the previously expressed idea that a definite relation existed between diabetic coma and acetonuria, while Gerhardt later on showed the occurrence of diacetic acid in the urine, a substance which has, clinically, even greater importance. Occurrence. — Physiologically, acetone occurs in the urine in very minute proportions, probably never more than .02 gram being excreted in twenty-four hours. Pathologically, more than 5 grams have been in the daily quantity of urine. The main conditions under which increased acetone is found may be briefly summarized as follows: 1. Alimentary, i.e. according to diet; withdrawal of carbohydrates; this may reach 0.7 gram after pro- longed dieting. 2. Diabetes, especially after some duration of the disease and with protein diet or increased fats. 3. Fevers (often with diacetic acid and /3-oxybutyric acid as well); infectious diseases, e.g. enteric fever, sepsis, pneumonia, exanthems, tuberculosis, acute in- flammatory rheumatism; in the fevers it occurs only in prolonged cases, probably because of the nature of the diet; acute fevers present no increased acetonuria. 4. Starvation and inanition; cachexia; early car- cinoma of stomach. 5. Digestive disturbances with autointoxication; peritonitis. 6. Pregnancy with dead fetus. 7. Nervous lesions and mental disease; tabes; general paralysis; melancholia, etc. S. Artificially induced general anesthesia (chloro- form). 9. Experimental — after extirpation of the solar plexus or of the pancreas. 10. Medicinal — phlorizin; chronic morphinism. [For a discussion of the source and mode of pro- duction of the acetone bodies, see the article Acidosis.] Clinical Significance. — In all probability the acetone per se is harmless and the toxic symptoms are produced by the diacetic and /?-oxybutyric acids; and possibly also others, e.^. lactic acid' or volatile fatty acids, come into action, too, at times. At all events, it is the acid intoxication (or excessive acidosis, as it has been called) that induces the serious changes whioh occur. Patients manifesting this acid intoxication usually get diabetic coma if no intercurrent affection occur to carry them off. The Prognosis, then, depends rather upon the evi- dence of acidosis than of acetonuria to a large extent, and Hallervorden has for this reason suggested the importance of frequent estimation of the ammonia eliminated, this giving a fairly accurate idea of the acid intoxication. (More than three grams of NH 3 in twenty-four hours indicates excessive acidosis, while if more than four grams exist, the onset of dia- betic coma is almost certain, even though due treat- ment temporarily diminish the amount of NH 3 elimi- nation.) This theory is proven, too, by Stadelmann's and Minkowski's observations, that diminished CO a was in the blood (i.e. less alkalinity), and by the fact, too, that in severe diabetes the sudden restricting to meat diet (i.e. acid) is often followed by coma. The acetone is to some extent, however, in definite ratio to the intensity of the diabetes, and the presence of a large quantity is of grave import — though not as a prodrome of approaching coma, as Hirschfeldt once supposed. Intercurrent fevers, e.g. pneumonia, may greatly increase the acetone temporarily, and with convalescence the quantity may return to its previ- ous amount. So it was in the case of a diabetic whose urine increased during an intercurrent pneumonia from 0.4 gram to 4 grams acetone, daily, and with convalescence the amount returned to 0.4 gram in the twenty-four hours; coma did not supervene and the patient lived for months afterward, until fatal marasmus came on. It is well, however, to follow the acetone excretion in diabetes, for its increase is so frequent with threatening symptoms; hence the bene- fit, at such a time, of judicious administration of carbohydrates. The diagnostic significance of acetonuria lies in the fact that its presence to any extent with glycosuria renders the diagnosis of diabetes certain. Tests. — Before testing for acetone one should ascer- tain the possible presence of diacetic acid. For this, Gerhardt's reaction is to be tried and the following three steps must be taken: Fifteen cubic centimeters of urine are treated with dilute (not too acid) ferric chloride so long as it gives a precipitate. The pre- cipitate (ferric phosphate) is filtered and more ferric chloride added to the filtrate. In presence of diacetic acid a claret-red color appears. A second portion of the urine is boiled and the same test repeated after cooling. A negative result should follow, because the diacetic acid was decomposed by the boiling. (If a positive result were again obtained it would indicate the presence of acetic or some other acid in the urine.) A third portion is next acidified with sulphuric acid and shaken with ether. The ether is removed and shaken with a very dilute aqueous solution of ferric chloride, when the watery layer becomes violet red or claret red. The color disappears on warming or after standing twenty-four hours. In the absence of diacetic acid we proceed to test directly for acetone. No single test for acetone is completely satisfactory; hence the necessity of employ- ing several as confirmatory evidence. One may use the urine as it is, although it is more accurate to resort first to distillation. About 250 c.c. of urine are boiled after faintly acidifying with sulphuric acid, and, a good condensation being secured, all the acetone will distil in the first 20 c.c. When diacetic acid is present the urine should first be rendered faintly alkaline and carefully shaken up in a separator funnel with ether (the ether must be free from alcohol and acetone). The removed ether is then shaken up with water, which takes up the acetone, and this watery liquid is tested. Qualitative Texts. — Lichen's Iodoform Test. — Treat a few cubic centimeters of the distilled urine (which should be freshly voided always) with some sodium hydrate and iodine potassic iodide solution and gently warm. With traces of acetone a yellow precipitate of iodoform occurs, and this will be recognized by its odor and by the hexagonal plates or stellate crystals. While this test is delicate enough for acetone, there are 70 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acctplifncttdln many other constituents of the urine and other sub- stances (at least seventeen) which yield a similar re- action. Among them is alcohol; hence the possibility of error from using an alcoholic solution of iodine to make up one of the reagents — which must, of course, be avoided. Gunning modified the test by using an alcoholic solu- tion of iodine and ammonia instead of the mixture mentioned above. A black precipitate of iodide of nitrogen results, and this, in the presence of acetone, gradually disappears, leaving the yellow iodoform behind. The test, though not quite so delicate, is more accurate, neither alcohol nor aldehyde produc- ing a similar result; and, moreover, it is eminently suited for clinical purposes, in view of the temptation to test without the time-absorbing distillation. Legal's Sodium Nitroprusside Test. — Treat a feu- cubic centimeters of the urine with two or three drops of a freshly prepared concentrated solution of sodium nitroprusside and add a thirty-per-eent. solution of caustic potash. A ruby red color appears, which changes to yellow. Any urine may give this reaction. But if acetone be present in pathological amount the addition of acetic acid changes the color to a purple- red or violet. Paracresol and creatinin give some- what similar reactions. In presence of the former, however, the yellow color changes to pink on addition of acetic acid, while with the latter a saturation with acetic acid gives a yellow color, soon changing to green and blue. Acetone, under similar conditions, gives a carmine color. Fehr modifies this test by floating the acetic acid on the urine as the color changes to yellow. A violet is produced at the line of contact, its intensity being proportionate to the amount of acetone present. Notwithstanding its frequent commendation for clinical purposes, Legal's test is certainly unreliable unless the urine be first distilled. Le Nobel's test is similar. One adds an alkaline solution of sodium nitroprusside (so dilute as merely to give a faint reddish tint to the solution) to the urine; a ruby red color is obtained, soon changing to yellow. On boiling and adding the acid a greenish-blue or violet results. Penzoldt's Indigo Test. — Treat the urine with a warm saturated and then cooled solution of ortho- nitrobenzaldehyde and add caustic soda. If acetone be present the liquid becomes first yellow, then green, and finally indigo forms, which may be dissolved in chloroform. Chautard takes fuchsin solution into which a cur- rent of sulphurous acid gas has been passed. This decolorizes the liquid and gives it a clear yellow tint. When added to urine containing acetone a deep violet color is produced. Reynolds' mercuric oxide test depends on the power of acetone to dissolve freshly precipitated mercuric oxide. A mercuric chloride solution is first precipi- tated by alcoholic caustic potash. The urine is added to this and the mixture well shaken and filtered. If acetone be present the filtrate contains mercury, which may be detected by the black color on adding ammo- nium sulphide. Reynolds' and Gunning's tests are particularly recommended for delicacy and reliability combined. Quantitative Test. — Huppert's modification of Mes- singer's is that most recommended; Lieben's iodo- form test being the method on which it is based. Acetone forms iodoform when treated in an alkaline solution with iodine. By treating the urine with a known amount of iodine one need simply estimate the quantity unused by the iodoform to know how much has been combined. This can be done by titration with sodium thiosulphate solution. For the details of the method, as well as for the methods for determin- ing ,3-oxybutyric acid quantitatively, the reader is referred to Neubauer-Huppert's " Analyse des Harns," 1910. Charles F. Martin. Acctozone. — The trade name of a grayish-white powder e posed of equal parts by weight of ben- zoyl-acetyl dioxide ami an inert absorbent powder of infusorial earth. The active ingredient, C.ll .< '< M >.- (>.('< )( 'II-,, is similar in structure to hydrogen dioxide, the hydrogen atoms being replaced by acetic and benzoic acid radicles. It occurs as a white crystalline powder, very slightly soluble in water or alcohol, melting at 98° F. (36.6° C), and d mposed by heat and by alkalies. It decomposes organic material in the presence of water and is consequently anti- septic and deodorant. It is employed externally as an antiseptic in gonorrhea, ulcers, tonsillitis, corneal ulcers, and suppurative nasal and aural affections, being applied in the form of powder, ointment with petroleum base, or solution in water or oils. Its chief use, however, is as an intestinal disinfectant in typhoid fever and dysentery; in the former con- dition especially it acts very favorably in reducing tympanites, controlling diarrhea, and destroying the odor of the stools. For this purpose the powder is added to warm water in the proportion of seven and one-half to fifteen grains (0.5-1.0) to the quart (1,000 c.c. or 1 liter), the mixture being thoroughly shaken and then, after standing for an hour or two, decanted. The dose of the decanted solution is indefinite, one or two quarts being drunk in the course of twenty-four hours. Acetozone inhalant is a mixture of benzoyl-acetyl dioxide 2, chloretone 1, and liquid petrolatum 107; it is employed in the form of spray in diseases of the nose and throat. Ointments of 0.1 to 1 per cent, strength should be made with a petroleum base, as acetozone is gradually decomposed by animal or vegetable fats. Acetphenetidin. — Aoetphexetidinum (U. S. P.), phenacetin, CjHsO.CjHj.NHCOCH,; "a phenol deriv- ative, acetparaphenetidin, the product of the acetyl- ization of para-amidophenetol." Occurs in the form of a white crystalline powder or glistening scales, without odor or taste, soluble in 92.5 parts of cold water, 70 parts of boiling water, 12 parts of alcohol, and 20 parts of chloroform. Phenacetin, like the other synthetic members of its class, was introduced as an antipyretic but has found its chief employment as an analgesic, in which respect it is less powerful, but safer and less depressant than acetanilide. In ordinary doses it has but little depressant effect upon the heart, but in overdose it reduces the hemoglobin of the blood to met hemo- globin, whereby the oxygen carrying power is dimin- ished and cyanosis is produced. As an antipyretic it may be of service in sthenic fevers, but in cases of adynamia it should be employed with caution as it is apt to cause profuse sweating and is debilitating. The latter effect may be obviated in a measure by combining the drug with caffeine. As an anodyne it is given for the relief of headache, neuralgia, gastralgia, and the lightning pains of tabes, but for the latter is inferior to acetanilide. It is sometimes useful as a sedative and mild hypnotic in cases of sleeplessness due to fatigue, nervousness, or slight pain. The dose as an antipyretic or analgesic is five grains (0.3), repeated in two hours if necessary. It is best given in powder, in capsules, or in compressed tablets. In the treatment of poisoning by an overdose of acetphenetidin, heat should be applied to the extremi- ties, and stimulants, strychnine or caffeine, be given; if cyanosis is pronounced, inhalation of oxygen may be serviceable. It is recommended that acetphenetidin be pre- scribed under its official title, and not as phenacetin, the latter being the name of the patented German preparation and sold at a much higher price. It is further recommended that, when prescribed as acet- phenetidin, care be taken to see that it is sold at the 71 Acetphenctidin REFERENCE HANDBOOK OF THE MEDICAL SCIENCES price of this drug and that it be not charged for at the rate of the expensive phenacetin. T. L. S. Acetum. — See Aceta and Vinegar. Acetylene. — See Gas, Illuminating. Acetylsalicylic acid. — See Aspirin. Achondroplasia. — Chondrodystrophy. See under Na n is m . Acidol. — See Belaine Hydrochloride. Acidosis and Acid Intoxication. Definition. — While acidosis and acid intoxication are frequently used as synonymous terms, strictly speaking they represent quite distinct entities. Acidosis is a condition, pathological or otherwise, in which an excess of acid products is indicated by an analysis of the blood or of the urine. It is impossible in many cases to distinguish whether an excess has really been formed, or whether the normal amount only has been formed and this amount has been inhibited from undergoing further oxidation. In conditions such as diabetes it is quite certain that the amount of acid products eliminated is in excess of what may be formed during normal metabolism. In this con- dition, at least, one is forced to assume that an ex- cessive production of acid compounds takes place. Acid intoxication, on the other hand, distinctly im- plies a pathological condition of toxic character pro- duced by acid products formed within the organism. Acid intoxication may also be produced by the administration of acids, chiefly inorganic. This form of poisoning is of importance, as it has a com- parative bearing on the general problem of acid intoxication. The Compounds Taking Part in Acidosis. — The com- pounds immediately concerned in the problem of acidosis are three: /3-oxybutyric acid, acetoacetic acid (diacetic acid), and acetone. They are usually termed the acetone compounds, although it would be more ad- visable to speak of them as the oxybutyric-acid com- pounds, for this substance is the starting-point in the formation of the other two. 3-oxybutyric acid has the formula: COOH I H— C— H H— C— OH I H— C— H I H This by oxidation is converted into acetoacetic acid: COOH I H— C— II I c=o I H— C— H I H which by losing a molecule of carbon dioxide from the carboxyl group is converted into acetone: COOH H H— C— II ■ I C=0 I H— C— H I H H— C— H C=0 I H— C— H k /3-oxybutyric acid was discovered simultaneously by Minkowski and by Kiilz, although Stadelmann had previously been led to suspect the presence of an abnormally large amount of an organic acid in diabetic urines. He mistook a decomposition prod- uct of /3-oxybutyric acid, a-crotonic acid, for the former. /3-oxybutyric acid as formed in the body is a levorotatory syrup, which has been obtained by Magnus-Levy in a crystalline condition. Ferric chlo- ride does not give a red color with this acid. The presence of acetoacetic acid in the urine was in- dicated by the reaction discovered by Gerhardt, who found that certain urines gave a Bordeaux-red color when treated with an aqueous solution of ferric chloride. Further investigation of this color reaction, especially by v. Jaksch, led this observer to believe that he had isolated acetoacetic acid from the urine. From the unstable character of this acid it is safe to say that it has never been separated from the urine in a pure condition. There is no doubt, however, that the substance giving the red color is really acetoacetic acid. All the tests which urines give under these con- ditions are those of aqueous solutions of acetoacetic acid. The acid is extremely unstable, and rapidly breaks down in solution into carbon dioxide and acetone. Acetone was discovered in the urine by Petters and by Kaulich in 1S57, and was the first of the acetone compounds to be detected. It is therefore from an historical point of view that acetone has lent its name to this class of compounds. When attention was first drawn to the connection between /3-oxybutyric acid, acetoacetic acid, and ace- tone, it was thought that acetone was the first sub- stance to be formed. This by synthesis with, possibly, formic acid would yield acetoacetic acid, which on re- duction might be transformed into /3-oxybutyric acid. This has since been shown not to be the case. The administration of acetone has never been followed by an increase in the amount of either acetoacetic acid or /3-oxybutyric acid, while the converse almost invari- ably happens. The administration of /3-oxybutyric acid or acetoacetic acid to diabetics or to persons ab- staining from food is followed by an increase in the ace- tone content of the urine and of the breath. Furthermore, these compounds make their appear- ance in the urine in the following order: acetone, aceto- acetic acid, /3-oxybutyric acid. They disappear in the reverse order, fl-oxybutyric acid being the first to van- ish. As /3-oxybutyric acid is the last to appear and the first to leave, one can only conclude that its appearance indicates the greatest departure from normal metabo- lism, and that, being the first product formed, it appears in the urine only when the capacity of the or- ganism to convert it to acetoacetic acid and acetone is impaired. One other acid product of metabolism may be mentioned which has played no inconsiderable role in some late theories of acid intoxication. This is -iarcolactic acid. It may be connected with the arc- inn,- com] nds, bul Hi" relation, biologically, is not clear. Its place in acid intoxication will be discussed when eclampsia is considered. The Source op the Acetone Compounds. — Theoretically all three classes of compounds which enter into tissue formation — carbohydrates, fats, and proteins — may be the sources from which the acetone compounds are derived. As, however, the carbohy- drates occupy such an exceptional place in the mechanism of acetone-compound formation, only the latter two classes, viz., proteins and fats can be considered as being acetone formers. For a long time it was thought that the fats and fatty acids alone were the source of the acetone compounds. [Von Noorden still holds to this theory. Although no doubt, he says, a certain amount of the acetone bodies are formed within the organism from protein (amino acids), this process is not extensive enough to I 72 reference handbook of the medical sciences \i IcIii-Ih account for all or even a considerable part of the pathological acetone formation. Hammarsten also says that while we cannot deny the possibility of a formation of acetone from proteins, certain facts nega- tive the theory that the acetone bodies arise entirely from the proteins.] It is nevertheless probable that the ! fatty acids occupy a more or less secondary place and that the proteins, or, what is the equivalent, the amino acids, are the chief source of these compounds. According as a substance produces or inhibits the formation of acetone, it is classed as ketogenic or ketoplastic, or antiketogenic or antiketoplastic. Bor- chardt further subdivides the ketogenic compounds into those from which acetone is directly derived, which actually break down, yielding acetone or one of its forerunners, and those which are merely ketoplastic, that is to say, only increase the output of these com- pounds in the urine or the breath, without having contributed directly to their formation. With regard to the fats, their action is complicated by the fact that they consist of two parts, fatty acid and glycerol. Glycerol belongs distinctly to the class of antiketogenic compounds, and its inhibitory action may be so great as to prevent any ketogenic action which the fatty-acid moiety may have. As to the tatty acids themselves, the results of feeding these substances to diabetics or persons in a state of inani- tion are not altogether in concordance. Joslin, taking into account the absorption of these substances by the intestinal wall, was unable to attribute to them a ketogenic function, and this was particularly - true of palmitic and stearic acids. Oleic acid was V ketogenic. His results are confirmed by Geelmuyden. [Magnus-Levy, who regards the fatty acids as the chief, if not the sole, source of the acetone compounds, says it is nevertheless unnecessary to restrict the inges- tion of fat is diabetes. It is not the presence of a large amount of fat that causes acidosis, but only the in- creased decomposition of fat. The occurrence of acidosis, he says, depends not so much (if at all) upon the formation of acids or upon their combustion.] It is well known that when fatty acids or soaps are fed, the acids pass through the intestinal wall in the form of soaps, and are immediately synthetized to neutral fats, the glycerol for this purpose being supplied by the organism itself. Borchardt considers that the greater part of any ketogenic function which the fatty acids may have is due to the abstraction of this necessary amount of glycerol, and they, therefore, do not act as direct acetone formers. In a control of this statement, Waldvogel has injected olive oil under the skin, and found no increase in the acetone elimina- tion, although when this substance is given by the mouth the acetonuria is increased. Absolutely neutral fats have been shown by Geelmuyden and by Hagen- berg to decrease the formation of acetone. Hence, one must conclude that the greater part of the ketogenic action of fats, especially those of the higher fatty acids, is due to their content in free fatty acids, which in their resorption combine with the antiketogenic glycerol, and so remove it from its sphere of action. As the chief source of the acetone compounds come the amino acids produced by the breaking down of p^ytein substances. Between many of the secom- pounds — leucin, arginin, serin, cystin, etc. — and/3-oxy- butyric acid there is a very clear chemical relation- ship. Further it has been shown by Embden that the perfusion of blood containing leucin through the surviving liver results in a prompt increase in the amount of acetone in the blood. Baer and Blum fed leucin to diabetics and obtained an increase in the amount of acetone compounds in the urine. Bor- chardt fed protamines containing a large amount of arginin, and also obtained a decided increase of acetone in the urine. Other amino acids have been fed by Embden and Salomon with like results. These are tyrosin and phenylalanin. On the other hand, glycocoll, alanin, glutaminic acid, and asparagin when circulated through the liver did not increase the acetone content of the blood. The laws which govern the formation of acetone from the substances above mentioned are chemically somewhat complicated, and even yel have not been completely worked out. They depend in part on the capacity of the organism to remove the amino group, and effect an oxidation at the 5-carbon atom (the atom next that carbon atom to which is attached the terminal carboxyl-COOH group). One example will serve perhaps to indicate the type of reaction which may occur. Leucin has the following formula: CH 3 CH 3 V ■ H— C— H C— NH, II C< I'OOH By a simultaneous removal of the amino group, re- moval of CO a from the carboxyl group, and subse- quent oxidation, one may have the following hypothet- ical series of changes taking place: CH 3 CH 3 CH 3 CH 3 \y CH, CH, CH r CH r I I CH H— C— H0 » h— C— H3 > I H— C— H II— C— NH,a H— C Ha | I COOH COOH COOH The final step here is isobutyric acid. If now this compound be oxidized at the /?-carbon atom, one obtains acetic acid and acetone as follows: CH 3 CH 3 CH 3 CH 3 \/ \/ Acetone CH C=0 J-H — H- H COOH H — C + H Acetic acid COOH As the acetates are easily destroyed by combustion in the organism, the acetic acid formed in the reaction disappears, and acetone is left. Similar reactions may be made out for the other amino acids which produce acetone compounds. Arginin, one of the diamino acids, is markedly ketogenic, according to Borchardt, and therefore substances containing large amounts of "} -i protamines, and consequently arginin, such as thymus and roe, are to be avoided in cases of acidosis. Reactions in which the /?-carbon atom is attacked by oxidation have been very completely studied by Knoop. By using compounds in which a straight chain of a fatty acid is linked to a benzene group, he was able to show that in every instance oxidation was effected at this place. The rule, therefore, seems to be a general one in the catabolism of fatty acids. The quesion whether the fatty acids or proteins are the principal source of the acetone compounds is thus fairly well settled, for it is seen that with the proteins the intermediary metabolism must take place through steps involving the formation of a lower fatty acid. Of very great importance from the standpoint of acidosis are the antiketoplastic substances. As has already been defined, these are the substances which prevent the excessive formation of acetone compounds, or reduce the amount which is excreted by the urine or the breath. As v. Noorden remarks, the extension of these substances is one of the most practical points in the therapy of diabetes. 73 Acidosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Outside of the alkalies, such as sodium carbonate, or certain salts of easily oxidizable organic acids such as sodium citrate, the chief members of this group are the carbohydrates. Without exception, all car- bohydrates have the property of decreasing the amount of acetone compounds, whether produced by starvation or by diabetes. Owing to the somewhat close similarity between these compounds and glycerol, the latter is next in antiketogenic action. It is unfortunate, however, that its use in diabetes is attended with a marked increase in the amount of glucose eliminated. Another member of this class is alcohol. Neubauer has shown beyond question that alcohol diminished acidosis to a marked degree, and at the same time appeared to diminish the amount of sugar excreted. Besides these, certain of the amino acids are quite antiketoplastic. Of these may be mentioned alanin and asparagin. The experiments with glycocoll and glutaminic acid were not altogether positive. It is worthy of note that Eppinger gave amino acids with what would have been fatal doses of inorganic acids, and was apparently able to effect recovery. His results, and the conclusions which he has drawn from his work, will, however, bear a control. Basing his classification on the content of antiketo- genic amino acids, Borchardt arranges the proteins in the following order: Protamin, histone, egg-albumin, pancreas, casein. Protamin gives the highest amount of acetone, while casein gives the least. What the mechanism is whereby the carbohydrates and certain of the amino acids are able to effect a reduction in the excretion of acetone compounds, is absolutely unknown. One reason for this lack of knowledge is the incompleteness of our information regarding the normal intermediary metabolism of car- bohydrates and of fats. These are two of the most difficult of the problems of biological chemistry. Waldvogel believes that the carbohydrates act by sparing the fats from combustion, but it has been shown repeatedly, and the present writer has confirmed the results, that only a very small quantity of sugar is needed in the marked acidosis accompanying the starvation in a case of pernicious vomiting of preg- nancy, for example, to abolish all signs of acidosis from the urine, and this without in the least affecting the general condition of the patient. The amount of carbohydrate which is necessary to prevent the appear- ance of these compounds in the urine is even smaller than that used to abolish them, once they are present, and is by no means large enough to protect any very considerable quantity of body fat. Nasse some years ago suggested a process of "sec- ondary oxidation" of the fats as a result of the pri- mary oxidation of the carbohydrates, and a somewhat similar idea has been put forward by Hirschfeld. None of these theories has any very definite experi- mental groundwork, and on the whole they are quite inadequate. To sum up as briefly as possible what is known about the source of the acetone compounds, it may be said that the higher fats probably do not form acetone compounds. Some of the lower fats and fatty acids have this property. Certain of the amino acids are probably the chief source of these substances, and form them by losing the amino (NH„) group, with the loss of carbon dioxide, and oxidation at the /?-carbon atom. Thus, in effect, the amino acids are trans- formed into lower fatty acids, which are changed to /?-oxybutyric acid and acetone. Substances which give rise to glucose in the organ- ism are antiketoplastic. The exception to this rule i< alcohol, which apparently has the most useful prop- erty of diminishing the glucose and acetone bodies at tin- same t ime. As in the combustion of proteins large amounts of sulphuric and phosphoric acids arc formed, these also probably play a part in acidosis. Salkowski showed, 74 many years ago, that the administration of taurin to rabbits was sufficient to produce enough sulphuric acid by oxidation to poison these animals. This was a case of endogenous acid intoxication from inorganic acids. The Conditions under which Acidosis takes Place. — In the healthy subject there is one condition which produces the elimination of acetone compounds; this is starvation. Not only complete inanition will bring about this anomaly, but the mere abstention of the in- dividual from carbohydrates is almost equally effec- tive. The length of the fast which is necessary is very short, less than twenty-four hours, and in all subsequent discussions of acidosis and the pathologi- cal significance of acetone compounds in the urine this fact must constantly be borne in mind. Indeed, a large amount of the clinical importance which has been attached to these compounds is rendered abso- lutely worthless when it is found that the observations have included no consideration of the condition of nutrition of the patient or of the amount and kind of nourishment which he consumed. Abstention from food for twenty-four hours is usually sufficient to cause the appearance of acetone in the urine, so that it can be detected with Lieben's test. From the twenty-fourth to forty-eighth hour acetoacetic acid makes its appearance, and at the same time 3-oxybutyric acid may be detected. Under-nourishment for any length of time may also cause acetone to appear, especially if the supply of carbohydrates has been insufficient for the needs of the body. That simple starvation may produce a very considerable acidosis is shown by the recent work of Brugsch on the professional faster Succi. This person was a man with a very decided amount of body fat. During the twenty-fifth day of his fast he eliminated acetone compounds equivalent to 13.6 grams of /?-oxybutyric acid. Similarly Satta has shown that carbohydrate starvation alone may lead to an acidosis equivalent to 20.0 grams of oxybutyric acid. This is a degree of acidosis which would be considered high even in cases of diabetes. That all fasting subjects do not react with the same degree of acidosis is shown by a parallel case reported by Brugsch. This was a woman suffering from stricture of the esophagus. She was in the very extreme of emaciation, as was shown at the autopsy, when it was found that even the plantar fat had disappeared. This patient excreted practically no acetone com- pounds. From these two observations Brugsch was led to conclude that the source of the acetone com- pounds was the abnormal metabolism of body fat. This is not the only conclusion which can be drawn from the results. It is also possible that the patient had adapted herself to an extraordinarily small caloric need, so that the amount of tissue which she consumed was adequate for her. Other observers have seen similar large amounts of acetone com- pounds appear during starvation. Nebelthau's case, in which sixty-six per cent, of the total nitrogen was eliminated as ammonia, must be included in this group. Having shown that simple inanition may produce large amounts of acetone compounds in the urine, one is led to inquire which of the three classes of food- stuffs it is that the abstention from is most effective in causing the increased elimination of acetone com- pounds in the urine when it is withdrawn from the diet. As might be expected from their marked anti- ketogenic action, the carbohydrates, and they alone, are the substances whose withdrawal causes the fea- tures of acidosis. One cannot therefore speak in general of a starvation acidosis, but simply of a carbohydrate starvation acidosis. The reason why, as a rule, one gets a less severe type of acidosis in carbohydrate inanition than in complete starvation is due largely to the antiketogenic constituents of the proteins, and to the glycerol content of the fats. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acidosis [Tests. — For a description of the various tests for acetone, the reader is referred to the article Acctonunn. (3-Oxybutt/ric Acid. — This may be tested for quali- tatively by I he method (if Hart. Add 20 c.c. of water and two diups of acetic acid to 20 c.c. of mine. Boil gently until the volume is reduced to 10 c.c. Add enough water to bring the volume back to 20 c.c. and divide the fluid equally in two test-tubes. Add 1 c.c. of hydrogen peroxide to one of the tubes, warm gently for about a minute and allow to cool. Then add to each tube seven drops of glacial acetic acid and three or four drops of freshly prepared solution of sodium nitroprusside. Add 2 c.c. of concentrated ammonium hydroxide carefully down the side of each tube, so as to make a layer over the urine mixture. At the end of four hours compare the tubes. If /?-oxybutyric acid was present the tube to which peroxide was added will show a purplish red ring at the junction of the ammonia with the urine, while the control tube will show no ring or only a faint brown in case there was much creatinin present. If there is no /9-oxybutyric acid in the urine the two tubes will show no difference. Sugar does not inter- fere with the reaction but albumin should be removed.] Pathological. Acidoses. — There is possibly no one urinary diagnostic feature in clinical medicine which has been called upon to account for such a diversity of symptoms as the presence of acetone and its allied compounds. A partial list of the affections with which they have been associated is as follows: cyclic vomiting in children; vomiting in pregnancy; eclamp- sia; fetal death; postoperative intoxications, espe- cially associated with narcosis; hyperthermia; pul- monary tuberculosis; malignant growths; asthma; toxic conditions following the use of antipyrin, mor- phine, atropine; carbon-monoxide poisoning, etc. It will be noted that almost without exception the conditions are those in which undernutrition or short starvation is prominent. In the acetonuria following narcosis one is usually dealing with abstention from food for a period of time quite sufficient to provoke the appearance of acetone in the urine in healthy Individuals. What is of paramount importance in the considera- tion of these cases is a statement of the amount of the carbohydrate intake and of its resorption. It is quite possible, for example, in children with a severe gastror intestinal derangement, that sufficient carbohydrate may have been given to protect the child from an acidosis, but owing to the digestive disturbance the antiketoplastic substance is not resorbed, and so one has to do with simple carbohydrate starvation. In a careful analysis of the clinical literature dealing with acetonuria in its relation to acid intoxication one is struck with the fact that little attention has been paid to this side of the question. Mohr, in his valuable review of diabetic and non-diabetic autoin- toxications with acids, has come to a similar con- clusion, and is able to see in the acetonurias of these various conditions nothing but the acidosis resulting from an insufficient supply of carbohydrates. Spe- cial mention might be made of pernicious vomiting in pregnancy, because here the acidosis as revealed by the acetone compounds, and more especially by the relative amount of ammonia in the urine, has been made a criterion whereby nervous vomiting might be distinguished from a more pernicious type. The present writer has criticised this view severely, and since that time his attitude has been supported by others who have had occasion to consider the subject. Certain it is that it is physiologically impossible to indicate operative interference in cases of pernicious vomiting in pregnancy from either an analysis of the urine for ammonia or an examination of the acetone- compound elimination. The etiology of eclampsia has been the subject of numerous investigations in which the starting-point has been the view that acid intoxication plays a prominent part, and quite recently Zweifel has nar- rowed down the toxic agent to sarcolactic acid, which IS found in the urine during and after the seizures. Dreyfus has repeated and confirmed Zweifel's results as to the presence of lactic acid in the urine, but is quite unable to find any etiological relationship between the appearance of the acid in the urine and the convulsions. It is altogether probable that lactic acid in the urine in eclampsia i.-- the result of insufficient oxidation and increased muscular effort, and does not in any way figure as a cause of the con- vulsive seizures. It has been repeatedly found by Araki and others in the urine in cases of carbon-mon- oxide poisoning and other conditions where its forma- tion certainly gave rise to no additional toxic effects. Diabetic Acidosis. — When one comes to the consid- eration of diabetic acidosis one is confronted with a problem of singular complexity. Obviously one is dealing with a condition- which is most favorable to the elimination of acetone compounds. There is in the first place the usual strict diet of fat and protein, which induces prompt acidosis in the normal subject; there is secondly the incapacity of the diabetic to util- ize the carbohydrate which is formed in the body from protein, and possibly from fat. This incapacity is often so complete that on a strict diet containing only fat and protein, for every gram of nitrogen excreted the patient excretes 3.5 to 4.0 grams of sugar. One is not astonished, therefore, that a patient in this con- dition, rejecting unused the sum total of the antiketo- plastic substances, excretes very large amounts of acetone compounds. It is now important to decide whether this acidosis is merely a carbohydrate inanition effect, or has a specific quality not seen in the acidoses previously discussed. In so far as one may judge at present, one must acknowledge that diabetic acidosis presents features which seem to indicate a specific nature apart from the influence of carbohydrates. The literature on the subject is extremely full, but v. Noorden has summed up the evidence in favor of its specific quality as follows. 1. Certain diabetics tolerating a diet containing sixty to eighty grams of carbohydrate eliminate no more acetone than a normal person on full diet. On transferrence to a carbohydrate-free diet the amount of acetone compounds increases, but finally on the same strict diet diminishes. 2. Others with moderately severe diabetes may eliminate, on a diet containing carbohydrate nearly to the limit of their tolerance, one gram or more of acetone. By transferrence to a strict diet the amount of acetone compounds increases, and continues to increase so long as the strict diet is adhered to. 3. In the third group, one may have individuals with certain characteristics of severe diabetes. They react favorably, so far as the disappearance of glucose from the urine on a strict diet is concerned; and yet under all circumstances they excrete large quantities of acetone compounds in the urine. In these cases one also gets marked variations in the amount of the acetone compounds excreted which have apparently no causal relation with the type of food administered. Von Noorden mentions a case in which fifty to sixty grams of /3-oxybutyric acid were excreted daily over a very long period of time. Further, there are marked individual differences in the way patients react with the same amounts and qualities of food. From these considerations one is forced to the conclusion that the acidosis of diabetes is not entirely due to carbohydrate inanition. Acid Intoxication. — While there can be no doubt as to the nature and severity of an acidosis due either to carbohydrate inanition or to diabetes, the matter is not quite so clear when one comes to connect the appearance of the acetone compounds in the urine with definite toxic effects. Each of the compounds in this series has in its turn 75 Acidosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES been the subject of numerous investigations as to its toxicity. Twenty grams of acetone produce some drowsiness in a man. The injection of one gram of acetone hypodermically had no effect whatever in the general condition of a girl. According to v. Jaksch, acetoacetic acid is not toxic, and even doses as large as a gram have been given to a frog without, the slightest effect. The results with /3-oxybutyric acid agree in most respects with what v. Jaksch obtained with acetoacetic acid. Most of the experi- ments, it is true, have been performed with the inactive acid, while the acid formed in the organism is the'levorotatory modification. Schwarz was, how- ever, unable to produce any toxic symptoms with eight grams of the active acid when given to a dog. Wilbur, working in v. Noorden's laboratory, has apparently obtained some slight degree of toxicity with the active acid. Very recently Desgrez and Saggio have claimed that both acetoacetic acid and /?-oxybutyric acid are toxic and cause a "demineral- ization" of the organism. The results of the French authors do not appear to be well enough founded to deserve serious consideration. So far as positive evidence is concerned, we have little of direct value to indicate that the toxemia which leads to diabetic coma, or, as Naunyn insists it should be called, dyspneic coma, is an intoxication produced by acid products. Nevertheless, the opin- ion in favor of an acid origin is so universal, and there is so little to supplant it, that one must admit a weight of opinion in place of a weight of evidence. The reasons for viewing dyspneic coma as an acid intoxication are as follows, and are given very com- pletely by Naunyn in his work on diabetes. In the onset of coma, the percentage of carbon dioxide in the blood falls markedly below the normal thirty to forty volumes per cent. This indicates that the amount of carbonates present in the blood, by which the carbon dioxide is transported from the other tissues to the lungs, has decreased. It has also been shown that preceding the coma there is usually a marked rise in the amount of acids, both acetoacetic and oxybutyric, but this is not always the case; for numerous cases of coma are on record in which the amounts of these substances were lower at the time of the attack than for long periods previously. Further, the sudden change from a mixed diet to one contain- ing fat and protein only has often provoked serious symptoms, which Naunyn believes are due to the flooding of the organism with acid products both of inorganic (sulphuric and phosphoric) and organic character. The clinical observations, too, on the use of sodium carbonate in preventing the onset of coma have many features which cannot be ignored, and lead one to believe that this type of therapy is of very real value. As much cannot be said for the use of carbon- ates during the coma itself. Here the reports which can be relied upon are almost hopelessly unfavorable. One point which has been suggested by some authors as to the relation between the acid products appearing in the urine and the onset of the coma seems worthy of notice. It is quite possible that there is no definite re- lation between the urinary products and the onset of the attack, for the reason that it is not the amount of acids which appears in the urine which conditions the coma, but the amount which is retained by the tissues. This would explain why patients such as v. Noorden's excreted large amounts of acid in the urine without having any symptoms of acid intoxication. The pro- ducts were eliminated as quickly as they were formed. On the other hand, a patient might form quantities of acids which would not be eliminated, and that which was retained might exert its toxic effect. In explanation of the inefficacy of the sodium carbon- ate treatment, it has been urged that the alkali circu- lates in the fluids which bathe the cells, but does in it actually reach those intimate cell structures where the toxic action of the acids is exerted. The most critical analysis of the theory of acid intoxication has recently appeared from Tangl's laboratory. Two of his pupils, Szili and Benedict, have undertaken to compare the findings obtained in intoxication with inorganic acids with those got in diabetes. Szili made a careful study of the effects of inorganic acids on rabbits, dogs, and goats. These animals were injected with solutions of acids, and analyses made of the blood by titration, and by the estimation of the true reaction of the blood by means of gas-chain cells. It was found that with lethal doses of acids the blood had a lower concentration of hydroxyl ions than distilled water; that is to say, the blood, compared with distilled water, had actually become acid. At the same time, however, it reacted alkaline to lacmoid paper. Of extreme importance in this series of experiments was the fact that it was possible to bring the animals immediately from a state of dyspneic coma by the intravenous injection of solutions of sodium carbonate. As a result of this work Benedict undertook a study of diabetic coma, following the methods employed by Szili. He sums up the reasons which have been given for believing that, diabetic coma is the result of poisoning by acids as follows: 1. Severe diabetics produce, besides the normal acid products of metabolism, excessively large amounts of organic acids. 2. The fixed alkalies, sodium, potassium, calcium, and magnesium, are not sufficient to combine with the continual excess of acids produced, and hence large quantities of ammonia are used for this purpose. 3. As increased acid production and increased ammonia elimination almost always precede the onset of dyspneic coma, and as /9-oxybutyric acid is not toxic in itself, one must assume that the toxemia is due to the acid character of the compounds when the amount of alkali formed is not sufficient for their neutralization, (o) The similarity between the coma produced by inorganic acids and the dyspneic coma of diabetes has long been recognized. (6) Blood investi- gations of diabetics have led to the assumption of a decreased alkalinity of the fluid. The carbon dioxide content is lowered even to four volumes per cent, instead of the normal thirty to forty volumes per cent. The points which stand in the way of believing that diabetic coma is an acid intoxication are the following: 1. Between the dyspneic coma and acid intoxica- tion by inorganic acids there is a fundamental differ- ence which can scarcely be explained away. While animals poisoned by inorganic acids may be made to recover almost immediately by the intravenous injec- tion of alkalies, this is practically never the case in the coma of diabetes. 2. It appears impossible to define accurately a dia- betic coma. One often finds cases of carcinoma, inani- tion, or hepatic disease in which the terminal coma has all the clinical signs of diabetic coma. 3. The assumption of an acidification of the tissues rests on the finding of a diminished carbon-dioxide content of the blood; but one finds a similar decrease in this value in other conditions without coma inter- vening. On the other hand, cases of coma in diabetes are on record in which the carbon-dioxide content of the blood was scarcely below the normal. In a control of these differences, Benedict investi- gated the actual reaction of the blood in cases of dia- betes by means of the gas-chain cell. The amount of titratable alkali was also estimated. Eleven cases of diabetes were examined, of which three terminated fatally in coma. In the three cases of coma the con- centration of hydroxyl ions in the blood was from 0.99X10-' to 0.42X10-', with an average value of 0.74X10 - '. In normal subjects there is a variation from 4.1 X 10~' to 0.41 X 10-'. So that in all cases the reaction was alkaline within what has been found to 76 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acids, Organic be normal limits. It has also been shown that in other conditions, e.g. pregnancy, the alkalinity may fall to 0.2x10-' without any danger to life. He therefore believes that neither the results of Szili nor his own investigations lend any support to the view that the dyspneic coma of diabetes is due to an intoxi- cation by acids. Folin doubts that the evidence presented by Szili and by Benedict is sufficient to discredit the acid- intoxication theory, and bases his conclusions on the fact that the Hungarian investigators have viewed the intoxication from the standpoint of the physical reac- tion of the blood, and that poisoning with large amounts of acids does not yield comparable results with the slow toxemia resulting from the production of an excessive amount of acid in daily metabplism. While the latter point is certainly well taken, the present writer cannot agree that the former criticism is justified. The acid effects of solutions of acids are due solely to the concentration of hydrogen ions. If the effects of the organic acids produced in the ab- normal metabolism of diabetes are- not those of hydrogen ions, one must assign a name other than acid intoxication to the toxemia resulting from their action in the organism. C. G. L. Wolf References. Naunyn: Der Diabetes Mellitus. \\ aMvogel: Die Acetonkorper. v. Noorden: Handbueh der Pathologie des Stoffwechsels. Bd. i. and ii. Borchardt: Zentralblatt fur die gesammte Physiologie und Patho- logie des Stoffwechsels, N. F. 1, 129 and 641, 1906. Folin: Journal of the American Medical Association, 49, 12S, 1907. Benedict: Archiv fur cUe gesammte Physiologie (Pfliiger), 115, 106. 1906. Szili: Archiv fur die gesammte Physiologie (Pfliiger), 115, 82, 1906. Wolf: N. Y. Medical Journal, April, 1906. Embden: Hofmeister's Beitrage, 7, 121, and 129, 1906. Mohr: v. Noorden's Sammlung klinischer Beitrage, No. 4, 1904. Joslin: Journal of Medical Research, 12, 433, 1904. Knoop: Habilitationsschrift, Freiburg, 1904; Hofmeister's Bei- trage, 6, 150. 1905. Dreyfus, Biochemische Zeitschrift, 190S v. Noorden: Die Zuckerkrankheit und ihre Behaudlung. 6th Edi- tion, 1912. Hammarsten: A Text-book of Physiological Chemistry. English Translation, 6th Edition. 1911. Magnus- Levy: Johns Hopkins Hospital Bulletin, 46, 1911. Acids, Organic. Drfi nitrons. — Acids are compounds which when dissolved in water are dissociated, yielding positively charged hydrogen atoms; these hydrogen atoms may be replaced by metals with the formation of salts. Organic acids are characterized by the presence of one or more carboxyl (COOH) groups in which the hydrogen atoms may be replaced by metals to form salts or by organic (alkyl) radicals to form esters. The basisity of an organic acid is determined by the number of carboxyl groups it contains: Fatty Acid Series, CnH 2n O,. — Fatty acids are found in the body chiefly in combination with glycerin in the glycerides or neutral fats of adipose tissue. They are also found combined with alkalies, as soaps, and, in small quantities, as free fatty acids. Free fatty acids occur in the intestine as a result of the breaking up of neutral fats in pancreatic digestion. Some of the lower members of the series are found free in blood and sweat. As we ascend the series, the molecules become more complex and the melting and volatilizing points rise. For each acid they vary slightly, accord- ing to the mode of preparation. Many fatty acids crystallize in characteristic forms. The following are of most physiological importance: Formic acid, H.COOH, is found combined as salts in minute traces in normal urine, and in increased amount in certain diseases with deranged meta- bolism, such as leueocythemia and diabetes. It is present in the stings of certain insects, giving them their irritating qualities. It is a colorless liquid, of strong odor, volatilizing at 100° C. Acetic acid, CH..COOH, is found in the intestine and sometimes in the stomach as a result of fermenta- tion processes occurring in carbohydrates and higher fatty acids. Its salts are present in normal urine in t races, and in increased amount in diabetes and leuco- cythemia. In the diseases named, it is also found in the urine combined with acetyl, CH 3 .CO, to form diacetic acid, CH 3 .CO.CH 2 .COOH. Acetic acid has a characteristic odor like vinegar, a sour taste, and forms transparent crystals which melt at 17° C. Propionic acid, CH 3 .CH 2 .COOH, occurs occasion- ally in sweat. It is present in the blood, urine, and vomit of certain diseases. It is the first fatty acid to form a neutral fat with glycerin. It has an odor like acetic acid and volatilizes at 142° C. Butyric acid, CH 3 .(CH 2 ) 2 .COOH, is found in the intestines and occasionally in the stomach, as a result of fermentations. It may be formed from the decomposition of proteins, carbohydrates, fatty acids higher in the series, or lactic acid. It is found in sweat, and traces have been demonstrated in blood and urine. It is present in milk and butter, combined with glycerin as butyrin. Butyric acid is an oily liquid, volatilizing at 162.3° C. and solidifying at -19° C. Isovalerianic acid, (CH 3 ) 2 .CH.CH 2 .COOH, is found in cheese, the sweat of the foot, and the urine in cer- tain diseases. It is a product of protein decomposi- tion. It is found combined as a neutral fat in dolphin blubber. It is an oily, colorless liquid, smelling like rotten cheese, and volatilizing at 176.3°. Caproic acid, CH 3 .(CH 2 ),.COOH, is found in the feces and sweat, also in cheese, is formed from putre- faction of proteins, and occurs as a glyceride in butter. It is an oily, colorless liquid, with a faint, unpleasant smell. It volatilizes at 205° C. and solidifies at - 18° C. Caprylic acid, CH 3 .(CH,) 6 .COOH, and Capric acid, CH 3 .(CH,),COOH, are found in sweat, in cheese, and as glycerides in butter. Ca- prylic melts at 16.5° C. and volatilizes at 236° C" Ca'pric melts at 30° C. and volatilizes at 270° C. Laurie acid, CH 3 .(CH 2 ), .COOH, and Myristic acid, CH,.(CH,) 12 .COOH, are present as glycerides in human fat and in butter, also combined as esters in spermaceti. Laurie acid melts at 43.6° and myristic at 53.8° C. Palmitic acid, CH 3 .(CH 2 ) 14 .COOH, is found as a glyceride in all animal fats and combined as esters of cetyl and myricyl alcohol in spermaceti and bees- wax respectively; it is also found combined with cholesterin in wool fat (lanolin). It melts at 62° C. Stearic acid, CH 3 .(CH,)i„.COOH, is found combined like palmitic acid in animal fats and spermaceti. It melts at 69.2° C. Margaric acid is a name sometimes applied to a mixture of palmitic and stearic acids. Arachidic acid, CH 3 .(CH,)„.COOH, is found in butter as a glyceride. It melts at 75° C. Cerotic acid, CH 3 .(CH 2 ) 25 .COOH, is found free in beeswax. Combined as cetyl ether, it forms the principal part of Chinese wax. The free acid forms granular crystals, which melt at 78° C. Acrylic Acid Series, C n H 2 n 2 - 2 0,. — Some of the higher members of this series form compounds with glycerin, resembling the neutral fats. The most important member of this group physiologically is — Oleic acid, CH 3 .(CH,)„.(CH) 2 .COOH; it is found united with glycerin in all the fats of the body, as a liquid fat, olein, which holds the higher fats of the fatty acid series in solution at the body temperature. It is more abundant proportionally in the fats of cold- blooded animals and in vegetable oils. Gh/colic Acid Series, C n H,n0 3 . — Carbonic acid, OH. COOH, is unknown in its free state, being doubt- less too unstable to exist. Its salts, however, are present in large quantities in the body, and play an important part in the alkalinity of the tissues and 77 Acids, Organic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES fluids. Its corresponding oxide, C0 2 , is the principal form in which carbon leaves the body. Glycolic acid, H.CHOH.COOH, does not occur in tic body. Lactic acid (better distinguished as ethylidene- lactic acid), CH 3 .CHOH.COOH, exists in three isomeric varieties: 1. Fermentation lactic acid is present in sour milk, and in the stomach and intestines during digestion. It is also found in small quantities in the muscles and brain, and in diabetic urine. It is a colorless or faintly yellow liquid of syrupy consistency. It may be regarded as a mixture of the two following from which it is distinguished by being optically inactive. 2. Paralactic or sarcolactic acid is the principal acid of meat extracts and of muscle, and is also found in numerous glands. It is present in the sweat in puerperal fever, and in the urine after severe fatigue, in acute yellow atrophy of the liver, and in phos- phorus poisoning. It is dextro-rotatory to polarized light. 3. A third levo-rotatory lactic acid has been obtained by the fermentation of cane sugar by a special bacillus. Oxybutyric acid, CH 3 .CH 2 .CHOH.COOH, found along with diacetic acid and acetone in the blood and urine of diabetes, is an odorless syrupy liquid, which mixes freely with water, alcohol, and ether, and rotates polarized light to the left. Oxalic Acid Series, CnH 2 n 2 — ( . — Oxalic acid, COOH.COOH, is found in small quantities in the urine as calcium oxalate, and often occurs in excess after the ingestion of rhubarb, strawberries, or cabbage. It is usually increased where the amount of uric acid is increased. It may be obtained in the laboratory along with urea and carbonic acid gas from the oxidation of uric acid, and it is believed to be formed from the latter in the body to some extent. Oxalic acid is a violent poison. It crystallizes from aqueous solutions in large, transparent prisms, which effloresce when exposed to the air. Succinic acid, COOH. (CH 2 ),. COOH, has occasion- ally been found in the urine after the ingestion of asparagus and other vegetables and fruits. It has also been detected in the sweat, the intestinal con- tents, and in the thymus and thyroid glands. It forms large colorless crystals which are unaltered by the air and which fuse at 180° C. Amino Acids are cleavage products obtained by the decomposition of proteins by various means and represent in part the nuclei making up the protein molecule. Chemically they are organic acids which contain one (monoamino) or two (diamino) amino (NIL,) groups. They may also contain either one (monobasic) or two (dibasic) carboxyl (COOH) groups in which the hydrogen is capable of being replaced by a metal or base. The most common and important amino acids are the following: I. Aliphatic (fatty) series formed from acids belong- ing to or derjved from the fatty acid series and in which the arrangement of atoms is essentially in an open chain. 1. Monoamino acids. A. Monobasic. Glycin, glycocoll or ammo-acetic acid, CH,.- NIL.COOH. Alanin hi- ,i -amino-propionic acid, CH,.CH.- NIL.COoII. Serin, oxyalanin or oxyamino-propionic acid, CIL 0H.CH.NH 2 .C00H. Amino-isovaleric acid, (CH,).,.CH.CH.NH.„- COOH. Leucin or a-amino-isobut vl-acetic acid, (CH 3 ) 2 .CH.CH 2 .CH.NH a .COOH. R. Dibasic. \ partic or a-amino-succinic acid, COOH.CH.- NH 2 .CH 2 .CO()ll. 78 Glutamic or a-amino-glutaric acid, COOH - CH.NIL.CIL.CLL.COOII. 2. Diamino acids. Lysin or «-s-diamino-caproic acid, NH 2 .CH,.- CH 2 .CH,.CH 2 .CH.NH,.COOH. Arginin or guanidin-amino-valeric acid, NIL- NH 2 .CNH.CH,.CH 2 .CH 2 .CH.NH 2 .COOH. 3. Acids containing sulphur. Cystin or <*-diamino-;9-dithio-dilactylic acid, (CH 2 .S.CH.NH 2 .COOH) 2 . Cystein or a-amino-^-thio-propionic acid, SH.CH,.riL.\lL.C.,.OH, cresol- sulpnuric acid, C,H 7 .O.S0 2 .OH, indoxyl-sulphuric acid or indican, (' Jl. .\.<>.SO„.OH, and skatoxyl-sul- phuric acid, C H,.N.O.S< >..< HI. These acids are all found in the urine, and are de- rived from the phenol, cresol, indol, and skatol which are formed in the intestines as a result of the putre- faction of proteins. Any circumstances favoring the latter process, such as intestinal diseases accompanied by obstruction, increase the amount of these acids in the urine. Aromatic oxyacids, of which the principal are paraoxyphenyl-acetic acid, C„H ( .OH.CH 2 .COOH, and REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acne paraoxyphenyl-propionio acid, C„H 4 .OH.C s H 4 .CO< Ml, are formed from tyrosin in small quantities in the in- testine and pass unchanged into the urine. Nucleic Acids. — These are acids rich in phosphorus, of complex and variable composition, found among the most characteristic constituents of cell nuclei. They combine with proteins to form varieties of nu- olein and nucleoprotein. Among the products of their decomposition, the most important are phos- phoric acid and the alloxuric bases, also known as the tanthin or still better as the purin bases. Uric Acid. — C s H t N 4 3 , trioxypurin, is found in adult human urine to the extent of from seven to ten grains per day, combined with bases to form urates. In birds and reptiles it replaces urea in the urine as the principal end product of protein metabolism. In man it is derived principally from the nuclei of broken- down cells and from the purin bases contained in the food. The extent to which it is formed from pro- teins in the body cannot be considered settled. For further details about uric acid, see Urine. Wesley Mills. William S. Morrow. Acids, Therapeutic Action of. — (See also under heading of each individual acid). In treating of the therapeutic action of acids, consideration is given to the stronger acids which possess all the chemi- cal characters of this group in a marked degree. The most important are sulphuric, nitric, hydrochloric, phosphoric, acetic, citric, and tartaric acids. Of other so-called acids, represented by boric, benzoic, ol- eic, carbolic, salicylic acid, etc., the chemical charac- ters of the true acid are either absent or gradually diminish until they are over-shadowed by other important therapeutic properties. When applied to the tissues, their local effect varies from the powerful corrosive action of sulphuric acid to the mild irritation of the vegetable acids. Sulphuric acid is destructive to all tissues, altering and destroying them beyond recognition. It is extremely hygroscopic, and this affinity for water is the cause of its great penetrating and diffused action. It combines with the albumin, fibrin, etc, producing a jelly-like mass which may be partially discolored and charred. The milder solutions simply coagulate and disorganize the albuminous structures. Nitric acid acts similarly, but is less severe. In addition to its corrosive effects, it produces a characteristic yellowish stain, which serves to distinguish it from other acids. A somewhat similar stain is caused by bromine and iodine, but marks of either of these are readily re- moved by a little caustic potash, while the nitric acid stain becomes of a brighter hue by the action of the alkali. Hydrochloric acid is very much weaker. It does not cause the same destruction of tissue as the other two acids, but the parts become white or whitish brown by its coagulation of the albumin; at times bulke and blisters may form. On the soft mucous surfaces, the strong acid may produce a swollen, structureless mass. The other acids, with the exception of glacial acetic acid, are simply irritants. In medicinal doses, the beneficial effects of dilute acids are marked, but how far this is due to their local action or is secondary to action after absorption, is still an unsettled question. After absorption they lose their acid character. They combine with the alkaline bases in the blood, and render it less alkaline, but never produce acidity. They are excreted as sulphates, chlorides, etc. The presence of hydroch- loric acid in the gastric juice is a true secretion of the gastric glands. As eseharotics the strong acids are a useful adjunct to the therapeutic armamentarium. Sulphuric acid is not so much employed as it was formerly, when it was a favorite reagent for removing morbid growths. Its painful effects and great pene- trating power are objectionable, and it is replaced by other caustics which are more easily controlled. This penetrating property, however, renders ii , as well as nitric acid, of value in bites and wounds of poison- ous animals. Nitric acid is always selected when any destruction of tissue is desired. It removes the necrosed tissue and produces a healthy growth of granulations. Hydrochloric acid is seldom used, although it was at once time often employed to destroy the membrane in diphtheritic throats. The use of acetic arid is almost limited to the slow removal of warty growths and the treatment of ringworm. In very dilute solutions all acids possess a cooling and refreshing action when applied to the surface of the body; they also exert an astringent effect upon the blood-vessels and sweat glands, as when employed to prevent or lessen the night sweats of phthisis. Nitro- iiydrochloric acid baths and compresses have been ex- tolled as a means of relieving the hepatitis of hot climates. When administered as a beverage all acids are most refreshing. This is well known in tropical countries. Lemonade, lime juice, dilute phosphoric, acetic, citric, and tartaric acids are universally employed. Their effervescing salts are particularly useful. They prove refrigerant and disinfectant, promote digestion, and if there is any diarrheal tendency, their astrin- gent properties become of service. Beaumont Small. Acne. — Definition. — Acne may be defined as a disease of the sebaceous glands of the skin and of the follicles of the lanugo hairs attached to them, thus being both a folliculitis and a perifolliculitis. It is characterized by their inflammation and suppuration and often by their destruction, with a resulting scar. The term acne has been qualified in accordance with various salient features presented by its lesions or with certain clinical characteristics predominant in a case, and there are therefore found in literature such terms as acne vulgaris, pustulosa, punctata, juvenilis, adolescentium, etc. All, however, rep- resent the same process. In addition to these, the name acne has also been applied to a large number of affections, which have nothing whatever in common with true acne, but which represent totally different pathological entities, and among these are included tuberculous affections, drug eruptions (iodine and bro- mine acne), or folliculitides of artificial origin (tar, oils, and grease, etc). For the sake of simplicity and definiteness, the disease will be treated of here under the heading of acne simplex — the more superficial form — and of acne indurata — the deeper-seated variety. Acne rosacea, being a compound process, will receive separate mention. Symptomatology. — Acne Simplex. — Acne simplex possibly represents the most common form of the disease, as it is the one developing particularly about the age of puberty and in young people. Instances have also been seen at a much earlier age, and like- wise later in life, about the climacteric. Apparently, it occurs more often in the female than in the male sex, but the ratio between them is probably more relative than exact. The lesions characterizing the affection occur without regularity or symmetry, though they are usually distributed bilaterally. Still, variations are met with, such as one side of the face being intensely attacked, and the other side only silghtly, and sometimes it is found unilateral. Acne occurs on the face especially, but it also often appears on the chest and shoulders, and sometimes on the upper arms, or it extends down the back even to the thighs. The lesions characterizing acne simplex are come- dones, papules, and pustules. In this variety of the disease, the comedo, or popularly the blackhead, as a rule constitutes a central point around which the inflammatory changes take place. These can usually be seen and traced in every case, and consist of redness 79 Acne REFERENCE HANDBOOK OF THE MEDICAL SCIENCES around the comedo, then formation of a papule, and lastly transformation into a pustule. Lesions may, however, arise independently of the comedo. The lesion having become pustular, remains as such for a few days; the redness then begins to fade and a crust forms, which falls off in the course of a few days or more, leaving a slight stain, or a scar, or a pitting. The pustular transformation does not, however, take place in all of the lesions. Many of them having reached the papular stage, remain in that form for a variable length of time and then gradually undergo involution. Neither do all the comedones become im- plicated and result in papules or pustules, but many persist in situ unchanged. In consequence, on an affected surface all stages of the disease are usually met with, and comedones, papules, pustules, crusts, stains, and scars are seen more or less aggregated i^G^mm? Fig. 16. — Section through a superficial acne lesion (acne simplex). (Author's drawing.) together without order or regularity, the whole constituting the condition known under the name of "pimply skin" or "pimples." The lesions of acne simplex present no especial subjective symptoms, though when handled the inflamed ones are sometimes slightly painful. Occa- sionally a burning sensation or itching is complained of. The scars and stains resulting from the lesions vary in degree, in number, and in size. In many cases, no scars are produced and the subsidence of the inflam- matory symptoms marks the end of the lesions. Others, however, leave decided stains and scars. The stains may remain for a few weeks only; but the writer has seen them persist for months with scarcely any change. As a rule, they gradually fade and ultimately disappear without leaving any pigmenta- tion or trace. In the cases in which scarring takc^ place, the scars often remain for all time, though occasionally the skin seems to smooth out entirely after a few years. These differences in the results of the lesions are naturally dependent upon the tissues of the individual affected, the formation of scars being commonly found in strumous subjects and in those suffering from malnutrition of various origin. When an acne lesion is opened and its contents evacuated, these will be found to consist of pus, blood, sebaceous matter, and the comedo, when this latter is present. After evacuation, the lesion heals rapidly and the process is at an end. Still just next to that gland, another may become attacked, and in that way the disease constantly renews itself, lesions appearing every day and the same train of symptoms repeating themselves for a varying period of time. Acne always runs a chronic course; that is, a limit of existence within which it ceases to recur cannot be made, and the comforting assurance so often given to young patients that when they reach legal age their affliction will disappear, is based upon fancy and not at all upon fact. The simple variety of acne may be present during the entire course of the affection, or it may become of the severer type — the indurate form — or it may be complicated by the development of a rosacea. The simple and indurate forms, however, very commonly coexist, one or the other preponderat- ing from time to time. Acne Indurata.— The deeper-seated variety of acne — the indurate form — presents clinical symptoms differing in degree and extent from those which occur in the type just described. Comedones are often present, but they do not constitute an essential portion of the process, nor do the lesions have their origin in connection with them. The efflorescences of acne indurata vary in size from a pea to a small nut. They originate deep in the tissues and enlarge slow-ly or rapidly, requiring some days and even a week be- fore softening. The inflammatory reaction is not limited to the gland alone, but affects the surrounding tissues, and while in cases in which the lesions arise acutely their color may be a bright red, in others it may be dull red and even purplish. In shape, great variations are seen, and the inflamed lesion may be rounded, or elongated, or irregular, and it may also, by the implication of several contiguous glands, give origin to a furuncular or abscess-like formation. The Fig. 17. — Section through an acne indurata pustule. (Author's drawing.) occurrence of the suppurative change is in some cases very active, and there is a rapid transformation of the indurated area into a pus cavity; but in others, only a small amount of pus forms in the central portion, and the hard and tense condition of the original lesion persists. Spontaneous rupture does not occur, and unless its contents are evacuated mechanically, the lesion may remain for days and even weeks, slowly undergoing involution. After it has been opened, it may refill again, and even many times, or until thor- ough evacuation of all its contents has taken place. Acne indurata is much more apt to leave scars than acne simplex. The scarring, however, occurs most readily in subjects of lax fiber, or who have strumous antecedents, or who are accustomed to empty the lesions by hard squeezing or other irregular mechani- cal means. The scars produced have no charac- 80 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES PLATE IV - * - : : - -- a < * r ~ - ^ £ REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acne teristics and are generally at first purplish and livid, but finally they become white in color. Keloidal or fibroid degeneration has been seen by the writer as a Bequela. This form of the disease attacks the same localities as have been mentioned for acne simplex, but it occurs on the trunk more frequently than the latter. The lesions may occur singly, discrete, and only few in number, or they maybe very numerous and more or less aggregated together. In fact, patches may occur on which they are so crowded that it is difficult to make out the separate lesions. \rne indurata tends to run a chronic course and to persist for a number of years. Only a few lesions may appear from time to time, or there may be severe out- breaks, and crop aftercrop may arise until the affected surface is covered with the manifestations of the process — papules, pustules, crusts, and scars — and every stage of evolution and involution of the disease be present at tin- same time. It is doubtful if spontaneous disappear- ance of the indurate form ever takes place, though Fig. IS. — Acne Cachecticorum of the Face. (From a photo- graph taken by Dr. George H. Fox.) such is not infrequent for the simple variety. In connection with both the simple and the indurate type of acne, seborrhcea oleosa occurs very commonly, the skin then presenting a greasy, oily aspect, being yellowish in color, with most usually the follicular orifices dilated, giving the surface a sieve-like ap- pearance. The process known as seborrhoic eczema {dermatitis seborrheica) is also a frequent com- plication, the skin then presenting, in addition to the acne lesions, scaly patches of irregular outline or patches covered with thin greasy squamae or even fatty crusts. It is in such eases that itching is generally complained of. Besides these, any other cutaneous disease may coexist with an acne. Acne Cachecticorum. — The form of cutaneous eruption to which the name of acne cachecticorum is given occurs in poorly nourished, marasmic, strumous individuals, though cases have been recorded which developed in those perfectly healthy. The process is Vol. I.— 6 generally associated with tuberculous glands of the neck and with lichen scrofulosum. The trunk and lower extremities tire must commonly the- seat of the eruption, though the arms may be affected and like- wise the face. The Lesions are of large size — pea to a nut ; they are dark red, purplish, and even livid in color; they are not tense or prominent, but fla' ened and flaccid. No sebaceous plugs are present, and the contents are scanty, consisting of a seropurulent fluid. They form crusts, and underneath these ulceration occurs. In some cases, the lesions become hemor- rhagic. After healing has taken place, a livid and purplish scar of irregular shape persists for a long time, finally becoming white. Occasionally, the hands are affected and become edematous and bluish-red, and covered with nodules and pustules. It is doubtful to-day whether this process should be regarded as an acne at all. In its course and general symptoms it differs greatly from acne indurata, though it is possible that the differences are due more to the soil Fig. 19. — Acne Cachecticorum of the Back. (From a photo- graph taken by Dr. George H. Fox. J conditions in which the process occurs than, to any special pathological causative factor. Still, owing to the presence of the tuberculous glands and the coexist- ence of lichen scrofulosorum, a tendency exists to regard it as a form of "scrophuloderma" and of tuberculous origin. Iodide acne and bromide acne are eruptions caused by these drugs when taken internally. The iodic acne occupies the same regions as acne in general, though it is very apt to be more disseminated over the surface. There are no comedones, but the lesions appear as an acute eruption of hard papules, which may enlarge and become pustular. General symptoms of iodism are usually coexistent. The bromide acne appears often on the face, but has a predilection for the hairy surfaces — scalp and eyebrows. The lesions are papules, pustules, and tubercles. They often form around the hair follicle and the lesion is pierced by a hair. Both of these may be caused by any iodine or 81 Acne REFERENCE HANDBOOK OF THE MEDICAL SCIENCES bromine compound, and though the eruption generally ceases with the cessation of the drug, it may, however, persist for months afterward. Acne picea, tar acne, occurs in those regions upon which tar has been used. The orifices of the sebaceous glands become blocked up with the tarry plug, which acts in a similar manner as the comedo and leads to perifollicular inflammation and the formation of a papule. Pustulation also takes place at times. The same condition may result from the use of chry- sarobin. The application of ointments, particularly in those regions in more or less constant contact with each other — the inguinal and the axillary regions, for instance — very often produces a follicular disturbance analogous to an acne, in so far that the lesions implicate the sebaceous glands and consist of papules which become, later, pustules. There may also be referred to here the folliculitis of the face and arms of flax spinners (Purdon), and the eruption occurring on the thighs, which is due to the oils and grease used by spinners in their vocation (Leloir). Pathology. — The pathological changes in acne are constituted by inflammation of a sebaceous gland, the occurrence of suppuration, and in a greater or lesser degree the destruction of the gland and the surrounding tissue. The cause of these changes may be of various origin and is certainly not a single specific one. It may be the comedo or other agent blocking up the follicular orifice, and acting as a foreign body causing perifollicular congestion and inflammation through some chemical change. The causal agent may, moreover, be some pathogenic microorganism present in the follicle prior to its closure, or carried to it through the circulation. The fact that certain microorganisms have been found to be especially associated with the production of pus has suggested that the acne pustule was the result of infection of the sebaceous follicle by some one or other of these pyo- genic germs. Most text-books on diseases of the skin give Staphylococcus albus as the cause of acne vulgaris in addition to the predisposing causes. Many investigators could get only Staphylococcus albus in cultures from acne lesions and this organism is undoubtedly an active factor in some, if not all stages of the disease. Unna in 1893 found a small bacillus in smears and sections from comedones together with the bottle bacillus and several forms of cocci. Only poorly nourished plate cultures of the bacillus could be obtained — no subcultures. Unna thought these bacilli were the cause of acne. Hodara in 1894 confirmed Unna's observations and grew the bacilli in mixed cultures but did not get any pure culture. Sabouraud in 1894 published his first com- munication upon his microbacillus of seborrhea but did not believe the organism to be the direct cause of acne. Gilchrist in 1899 isolated a bacillus in pure culture from acne vulgaris lesions which be believed to be the cause of the disease. In 1903 Gilchrist confirmed his previous work by finding the Bacillus acnes present in 240 smears from 86 patients; and pure cultures of the organisms were obtained from 62 lesions. He also found that the sera from patients suffering from severe acne caused clumping or agglu- tination of the Baccillus acnes even when diluted 1-100, which led him to think that the anemia, coated tongue, and constipation were probably the result of acne and not predisposing causes of the disease. Engman con- siders the organisms described by Unna, Sabouraud, Gilchrist, and himself to be identical. He found the organism was grown only with the greatest difficulty and was unable to obtain subcultures. Fleming, Western, and Lovejoy have since noted the constant presence of Bacillus acnes in the lesions of acne. Smiley reports 100 cases of acne vulgaris in which the acne bacillus was present in all. In eighty-six per cent, of his cases the accompanying organism was the Staphylococcus albus; in ten per cent, he found the Staphylococcus albus and aureus together; in three per 82 cent, the Staphylococcus aureus alone; and in one per cent, the Staphylococcus citreus and albus together. In the writer's opinion Bacillus acnes may be the cause of the acne lesion, but it certainly is not the only cause. The bacillus can frequently be iso- lated from the sebaceous follicles of the nose of people who have never had acne. Experience and the ob- servation of a great many cases nave shown that the various functional and pathological conditions men- tioned in the paragraph on etiology play a most important part in the production of the eruption. Under the influence of these various etiological factors the resisting power of the skin is lowered. As a result the acne bacillus is enabled to assume patho- genic properties where before it had existed as a harmless saprophyte of the skin. Pathological Anatomy. — According to many writers the starting-point of the inflammatory change is around the follicle of the lanugo hair attached to the gland, the latter becoming only secondarily impli- cated in the process. The writer has, however, frequently found the hair follicle absolutely intact and not concerned in the pustular formation. The inflammatory changes always begin around the follicle — that is, it is primarily a perifolliculitis. The tissues are infiltrated with round cells which are located at first around the network of blood- vessels supplying the sebaceous gland attacked. Unna states that the infiltration consists of plasma, large fusiform " mast " and a few giant cells, leucocytes being found only when suppuration has occurred. The degree of infiltration varies in different lesions and cases. The writer has found that in acne simplex lesions, infiltration is more superficial and located about the duct and upper part of the gland, while in the indurate form it is deeper and around the body of the gland especially. It may also extend widely throughout the cutis; and several contiguous glands becoming affected, they melt together into one inflammatory and suppurating area. The peri- follicular inflammation having extended to the gland, its parenchyma becomes infiltrated, its cavity is distended, and its walls ruptured in places. Its con- tents are then composed of serofibrinous fluid, sebaceous debris and leucocytes, some intact glandular epithelium, and often the comedo. In acne simplex the gland is not always destroyed, but in acne indu- rata it generally is. The same changes may affect the follicle of the lanugo hair attached to the gland. Etiology. — The etiological causes active in the production of acne, whether of the simple or indurate variety are manifold, and the process cannot in any sense of the term be regarded as of specific origin. Whether the many disturbances or systemic condi- tions found in connection with these cases are to be estimated as of causative importance, or as simply of predisposing effect, is a question which will be deter- mined when the pathological origin of the disease is absolutely established. Until then it can only be said that without their proper valuation and con- sideration, no case of acne can be understood or its needs correctly estimated, for it is more upon these etiological factors that treatment should be based than upon any other feature presented by the proc- ess. Age plays an important part, as the inception of the disease in the large majority of cases is at or about the time of puberty. Still it occurs at other ages, and the writer has seen it develop at every period of life between puberty and the climacteric, and even later. In youth, acne simplex is most common, but acne indurata occurs most frequently after twenty-five. That it tends to disappear at the age of twenty-one — a belief so current among the laity and unfortunately the general medical profes- sion also— is an unwarranted assumption, due to the fact that many patients have at that age recovered from one or another disturbance of nutrition incident REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arnr to their development, and occurring during the pe- riod in which stability of their tissues was in a stage of transition; that is, major etiological causes of the disease had by that time been removed by nature, by general treatment for other systemic condition':, nr by greater care of the functional and general health on the part of the individual afflicted, through educa- tion and possibly observation of the relation existing between the eruption and some deviation from normal health. Menstrual and uterine disorders are frequently accused as predisposing factors in the production of acne, but still too much stress should not be laid upon them alone, since the cause of the menstrual disturb- ance may more properly be the important factor. At any rate, an aggravation of an existing acne will commonly occur before, during, or after a menstrual epoch. And yet the abnormal conditions which affect this function may be entirely removed, but the eruption will persist; or the acne may be radically eured, "hile 'he functional or other disturbances of the uterine organs remain unchanged. In assocation with the process, all other forms of functional and nutri- tive disturbance are also met with. Constipation is very frequent and not uncommonly chronic catarrhal forms of diarrhea. Chlorosis or anemia of variable grades and debility of various origin are often the basic factors. Gastric and intestinal dyspepsia are common, though in my experience it is most usually fermentative intestinal indigestion which is of impor- tance. Dilatation of the stomach has been stated to be particularly common in these cases, but it is undoubtedly exceptional. Mental and physical ex- haustion, excesses of any and every kind, masturba- tion, urethral irritation, a sedentary life, excessive exercise, the gouty, rheumatic, or strumous consti- tution, all must be mentioned as causes of acne in themselves or through their influence upon the systemic health. But if analysis is applied to all of these, it cannot be evident that the whole may be comprised in the category of lowered or debased nutrition, as all are productive of more or less marked nutritive disturb- ance of the organism. In consequence, the etiology of acne can be briefly stated to depend especially upon some disturbance occurring in the functional or systemic health of an individual, which results in disordered or lowered nutrition. External and local causes, however, also play a certain part in the pro- duction of the disease. Among these, there may be mentioned exposure to cold winds, to irritation of various kinds, inattention to cleanliness, etc. The face, the locality most generally affected, is that surface especially and constantly exposed to such factors as changes of temperature, to dust and drift of every description carried by the winds, to irritating influences of many kinds, and the fact that it is attacked so disproportionately in frequence to other surfaces equally or almost as rich in sebaceous glands would suggest that these various external agents and causes have an influence in developing or at least in aggravating many, if not all, cases of the disease. As particular causes of acne, the atrophic form of rhinitis has been mentioned, and recently a German colleague has claimed that all cases of the process owe their origin primarily to some slight or severe ulcerative or erosive process in the nasal cavities, which allows entrance of pyogenic germs into the lymphatic circulation. The acne due to the use of iodine and bromine compounds has as its direct inducing cause one of those substances, and is a drug eruption; not an acne in a strict sense, but one of artificial origin. The same may be stated in regard to the folliculitis due to the closure of the follicle by tar — after use of a tar ointment — and known as acne picea; while the many other processes dubbed acne of one kind or other, having nothing in common etiologically with acne simplex and indurata, should all be strictly disassociated from these. The effect of diet upon the disease is of some importance, since it may originate the process, through the functional disturbances which it may create, or it may aggravate an already existing acne. Among the articles of diet which may be particularly men- tioned are sweets of all kinds, pastries, oatmeal, cheese, nuts, highly seasoned and rich foods, shell- fish, etc. Milk in certain individuals appears to have the effect of causing an outbreak of lesions; so also has cream, fermented drinks, such as beer, etc., champagne, and syrups with soda or natural waters. Diagnosis. — There should be no difficulty in making the diagnosis of a case of acne. Popularly known as "pimples" or a "pimply face" or an attack of "blackheads," it is so common that its recognition should be immediate. Especially is this the case with acne simplex, in which the comedo plays so important a role; but acne indurata may at times offer some points of doubt. The papular form of eczema may be differentiated by its occurrence on the extremities as well as on the face, and it is never limited to the latter. Its lesions are smaller, often crowned with a minute vesicle, and they tend to coalesce into patches; they are very itchy, and when opened do not contain sebaceous debris. The vesicular or pustular elevation is superficial and results in the formation of epidermic scales and small exudation crusts. The pustular syphilide may be mistaken for acne, and vice versa; and so much is this the case that one form of syphilitic eruption has been named acneiform. These lesions may be limited to the face, but they are more often coincident with syphilitic manifestations on other parts of the body or on the mucous membranes. They tend to form groups, to dry and become covered with crusts; and when these are removed, a punched-out ulceration filled with seropurulent fluid and bounded by a more or less infiltrated wall is found. Many mistakes in diagnosis are made between an indurate acne and the superficial gummatous syphilide — the so-called tuberc- ular syphilide — especially when the latter is situated on the nose. But the error should not occur when it is borne in mind that the syphilide as a rule is circumscribed in its occurrence, its lesions are grouped, indolent, undergo softening and crust formation, and beneath the latter ulceration occurs. The process very usually extends slowly in an excentric or serpiginous manner, leaving more or less marked cicatrices. Acne indurata, on the other hand, runs a more acute course, is painful and furuncular in aspect, occurs here and there without reference to preexisting lesions, does not tend to form groups, heals up rapidly after evacuation, does not ulcerate nor tend to progress in a serpiginous manner, and frequently leaves no scar, or at the most one superficial and ill defined. There is a papular form of erythema occurring at the menstrual epoch in women which is very usually con- founded with acne. It is papular in character, though occasionally a pustule occurs. It appears on the face especially, but sometimes over the neck and shoulders. Its appearance is brusk, a few days before, during, or just after the menstrual epoch. It may consist of a few or of many lesions, which are frankly inflammatory and about the size of a small pea. They do not contain any comedo or sebaceous matter; they itch and burn, persist for a few days to a week, and then subside, to reappear, however, at the time of the next period. This eruption, purely a reflex papular erythema, is usually regarded as an acne, but it should be strictly separated from it. Prognosis. — The prognosis of an acne is favorable, and it can be said that all cases of the disease are curable, provided that the etiological factors existing in any given case are correctly estimated, and that 83 Acne REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the therapeutic efforts are carried out carefully and systematically by the patient. Acne also may and does disappear spontaneously, but that is the case when the one or other cause of the process has also been removed by course of time, improvement of general somatic conditions, etc.; but in view of the disfigurement, scarring, and changes which may occur in the skin from the disease, it is not advisable to wait for a spontaneous involution and to leave the patient without such proper care as will keep the process within bounds or gradually cause its entire cessation. In giving to a patient the prognosis of his or her acne, it should also be borne in mind that the same causes can produce the same effects, and that the complete or lasting cure of the eruption will therefore depend upon the individual's avoidance of the particular cause or causes or factors which have been found to be the basis for the existence of the disease in any given case. As to the length of time needed to cure a case, definite statements should not be made, since the duration of treatment will have to depend upon the response of the patient to the remedial agents made use of, the care and system with which the orders of the physician are carried out, the age of the patient, and particularly upon the pos- sibility of removing the etiological factor or factors. Still, if not absolutely cured, no case should be dismissed as incuraDle, as all can be very materially benefited by proper care. Treatment. — The methods, procedures, and reme- dies pertaining to the treatment of acne are mani- fold and various, being such as have to do with the general systemic health, and such as are local and applicable to the lesions themselves. In no sense of the term is there any specific medication in vogue or any drugs which can be regarded as specific, but every case has to receive such treatment as is indicated by the conditions found to exist. The statement just made refers especially to the internal and general systemic care, and in these particulars there is no disease in which, as it may be put, " individualiza- tion" of treatment is so necessary and called for. As a rule, no two cases can be treated alike, but each must receive such special advice as may be judged to be required, after a thorough investigation into the bodily and functional health of the patient, his habits, mode of life, diet, etc. Under these circum- stances, should constipation be the factor in the case, it should be relieved by cascara sagrada, aloin, or some other remedy affecting the bowels, or by means of diet, proper exercise, cold douches, etc. Gastric or intestinal indigestion, fermentative processes, should be appropriately combated by dietary measures, the mineral acids, pepsin, etc., or by intestinal an- tiseptics — resorcin, sulphocarbolate of soda, salicin, charcoal, etc., and by such other measures as are in- dicated for these conditions. If debility or anemia exists, then tonics are called for: iron, mix vomica, mercury, the vegetable bitters, feeding up, general hygienic methods, etc. The ferrum reduetum, the carbonate, and the dry sulphate of iron have proved the best in my experience; hemogallol is particularly good when the stomach rebels against the other forms or when constipation exists. Except to tuberculous subjects, the iodide of iron should not be given, owing to the possibility of the iodine causing an eruption. When administering iron in cases of acne, the blood should be tested at the beginning of its use for the percentage of hemoglobin, and retested every two to three weeks. Only in this way can certainty be had that the iron given is being assimilated and the blood state is or is not improving. Practi- cally, Fleischl's hemometer answers all requirements for testing. For strumous subjects, cod-liver oil. the hypopnosphites, and the malt preparations are e pecially valuable. If, on the other hand, the acne occurs in gouty subjects, in those who are rheumatic or plethoric, who show evidences of deficient elimina- 84 tion, then alkaline mixtures, the potassium salts — ex- cept the iodide and bromide — lithia, saline purgatives, colchicum, the salicylates, strict regimen, etc., are of the greatest service. In other words, every indica- tion obtained from investigation of the patient's history should be duly estimated and receive such attention as it requires. It is useless to take up each seriatim, but all should be considered together in order to obtain as rapid progress as possible. The effects of calcium sulphide are illusory: none when given alone; but when exhibited together with dietary regulations, with other internal and local treatment, then improvement is seen in the case. But the result is obtained by those same measures when no calcium sulphide is administered. Arsenic is of use under certain conditions, but should not be regarded as a specific. As a rule, more harm than benefit is done by it. It is of value in certain cases in which anemia or debility is present. In acute examples of the disease it is contraindicated, but it may be of benefit in those which are chronic in type. In those acnes which are complicated by a seborrhea oleosa, or in which the process is sluggish and the lesions are indolent and leave congested stains, ichthyol internally is frequently of value. Beginning with five-grain doses three times a day, the amount may gradually be increased until gr. xv. ter in die are being taken. The drug is harmless, and for its best effects should be continued for several months. The question of diet is of some importance, but yet it should not be carried to an extreme, nor be regarded as the keynote of the treatment. In general, it may be stated that the diet should be composed of nutri- tious and easily digested food, and the various arti- cles chosen or forbidden should depend to the greatest extent upon the digestive conditions in existence in the individual case under care. As a rule, I have found that it is advisable to forbid in all cases such articles as are comprised under the heading of sweets — desserts, candies, jams, preserves, pies, rich pud- dings, etc. — and also oatmeal, cheese, and nuts. Besides these, the diet should exclude stimulating, highly seasoned, and indigestible foods of all kinds. Oysters are allowable, but lobsters and crabs will be found injurious. Clear soups, plainly cooked fish, roast and broiled and boiled meats, poultry and game, vegetables of all kinds, salads with plain vinegar and oil dressing are perfectly allowable for all cases, but at the same time the diet in these as well as in all particulars will have to be varied according to the necessities of the individual case. In may thus be found that in one milk, cream, butter, and fats will be beneficial, while in others they will be injurious; in some, a light claret or Rhine wine with the meals is distinctly beneficial, but in others all wines will be harmful. The same remarks are pertinent as regards beer, alcohol, tea and coffee; and on the whole, it may be stated that so far as diet is concerned, the same rule should be followed as has been laid down for the internal medication of acne — that is, it should be made to conform to the needs and the require- ments of the individual afflicted, and not with a view of furnishing a specific regimen which shall of itself remove the affliction. General hygienic laws should also be enforced. Exercise in moderation, but not, however, to the excessive point it is carried to-day, is of value, and so also is a change from a sedentary to an active life. Attention to personal cleanliness, to bathing, to early hours is clearly indicated, and dissipation and excesses of all kinds should be avoided. The local treatment of acne is of equal importance with the internal and with the general care of the patient, for by these means the lesions of the disease ran be removed and a healthy action of the skin can be brought about, and that even before the pre- disposing causes have been entirely disposed of. Many cases, moreover, can be cured by external REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acne treatment alone, but the writer has failed so far to obtain such a result from exclusively internal care. Both, in reality, should go hand-in-hand in order to get the best and most rapid cure of the process. The first requisite in the local treatment is the use of soap and water. The surface of the skin, the seat of an acne, should be thoroughly washed night and morning. Any good toilet soap is all that is neces- sary, but a marble or sand soap has been recom- mended, as well as the Tr. saponis viridis. Super- fatted soaps containing resorein, ichthyol, sulphur, or mercuric chloride are also advised and used, but unless left on the surface over night, for instance, they offer little advantage over a plain, pure soap. Tar soaps are decidedly injurious in these cases, particu- larly if rubbed info and left on the skin, inasmuch as the tar may lead to the development of an acne picea. The water should be fresh and cool — about the temperature of the room; and in the writer's opinion and experience, hot water is injurious. Still, it is recommended by many as of value when applied for a number of minutes every night at as high a temperature as can be borne by the patient. Face straining is also advised by some, the external remedy ordered being afterward rubbed into the skin. The writer certainly cannot vouch for the value of either one of these procedures, as he himself has never found them other than objectionable, increasing the amount of the eruption, inducing often a seborrhoea oleosa, accompanied by a relaxed condition of the skin and dilated follicular orifices, and causing the skin to have a sieve-like appearance. He has also found that these procedures were liable to cause a persistence of the process and to occasion frequent relapses. The same statements he would also make in regard to facial massage, so frequently recom- mended and used to-day, as in his experience he has found that it often causes an outbreak of acne and invariably aggravates a preexisting one. Still these may in some cases be beneficial, but they certainly are not adapted for all, and should not be made use of as regular modes of treatment. The comedones should be dealt with according to the directions given under that section. Curetting, both for them and the acne lesions, has been recom- mended by various writers — Hebra, Jr., Fox, Brocq; a dermal curette is used, and the face is gone over and thoroughly scraped once every week or ten days. The operation is rather painful, and though at times there may be rapid improvement, yet unless the pa- tient is treated locally and internally at the same time, the relief is only temporary and a marked relapse is apt to follow. I wish to emphasize this statement because in a large number of cases which have come under my observation the previous treat- ment consisted solely of repeated curetting, and yet the relief afforded had been only temporary. Inci- sion of all the lesions with a sharp-pointed bistoury and complete evacuation of their contents constitute very desirable steps. When the acne lesion has been quite large, or a veritable abscess has formed (through the coalescence of several lesions), or such an abscess has reformed despite repeated openings with the knife, it is advisable to swab out the cavity with pure carbolic acid or with pure or fifty per cent, ichthyol. An ordinary match slightly sharpened is all that is necessary for conveying the antiseptic into the cavity. For lesions which are indurate, indolent, and obstinate, not containing pus, linear scarification has been recommended by Vidal and electrolysis by Brocq. The latter procedure invar- iably, however, causes more or less marked scars. For the obstinate lesions, the writer has obtained good results from the emplastrum hydrargyri, or from pure ichthyol, or from the unguentum hydrar- gyri nitratis diluted one-half or more. The local agents and remedies which have been used and recommended for the treatment of acne are innu- merable and of the urn I various kinds. Yet all which will be found beneficial possess some degree of antiseptic action. The application chosen should vary according as the process is acute in character, or partakes rather of the indolent and chronic type. For the former, soothing applications should be used, and for the latter those which are stimulating and capable of causing a certain amount of active reaction in the tissues. In all cases, liquid agents, solutions, etc., are far preferable, and only occasion- ally are salves and greases advisable. When the eruption is acutely inflamed, there can be used a lotion of R Magnesias carbonatis, Zinei oxidi, aa, gr. xv.; Acidi carbolici, gr. x. (or Acidi borici, gr. xv.j or resorcini, gr. v., etc.); Aquae rosae, gi. M. Cala- mine may be substituted for the magnesia in the lotion, or aqua calcis can be used instead of the rose water. Other lotions suitable for these cases are: Liquor plumbi subacetatis diluti, or R Bismuthi sub- nitratis, 3ij.; Ichthyoli, gr. xv.; Aqua; rosae, aqua? calcis, aa 5 ss. M. If the patient's skin is a dry and harsh one and a seborrhea oleosa does not complicate the acne, then an ointment can be used. Suitable ones would be: R Acidi salicylici, gr. xv.; Zinci oxidi, gr. xl.; Unguenti aquae rosae, 5i.; or a two per cent, ichthyol ointment, or one containing boric acid, three to five per cent., etc. The remedy chosen should be kept more or less constantly on the affected surface, in order to obtain the best results, and if possible it should therefore be used both day and night. The large majority of acne cases being, however, of the chronic type, a greater choice of remedies is needed, and they are also required when the acute stage of the disease has subsided and the case has also become indolent in character and course. Of especial value are applications containing sulphur. It may be used in powder form mixed with starch in the proportion of one to four, or as high as one to one, that is, equal parts, But it is in lotions that sulphur is most useful, though many recommend it in the form of a ten-per-cent. ointment or paste. R Sulphuris sublimati, gr. 1. to 5%; Crete pra?parate, kaolini, aa_5 ij-; Unguenti aquae rosae, §i. M. Apply freely at night and remove with soap and water next morning, and then rub in well a two-per-cent. salicylic or other mild ointment, or apply a three- to five-per- cent, boric-acid lotion several times through the day. A very strong resorein paste is also of benefit at times. Its strength may be from ten to twenty-five per cent. or even more according to the indolent nature of the case. It should be applied by the physician and its effects closely watched, as resorein has a very power- ful reactionary effect on the skin, and will cause a diffuse peeling off of the epidermis. The reaction produced may give some very undesirable results, but when the procedure is carried out with care it is usually of great benefit. The number of applications necessary will vary in each case, and the paste should be discontinued when the epidermis has a seared, yellow look, and exfoliation is imminent; a mild, soothing salve should then be substituted for it. The process may be repeated a number of times, but a milder resorein paste should be used after the first peeling has occurred. This method, which is rather heroic, necessitating the patient's confinement to the house, is of great value, but necessarily of restricted use, and, the same results being obtainable by milder measures, it should be reserved for obstinate and rebellious cases. In the severe forms of acne indurata and acne pustulosa Bier's hyperemic treatment may be found useful. Suitable cupping glasses may be applied or an elastic bandage round the neck may be worn. There are a large number of lotions in use for acne, which, together with other ingredients, contain some proportion of sulphur. Of these, there may be men- tioned: R Sulphuris sublimati, 5 ij.; JStheris, spir- 85 Acne REFERENCE HANDBOOK OF THE MEDICAL SCIENCES itus vini, glycerini, aa .> ij.; Aqua calcis, aquas rosas, aa 5 iv. M. (Crocker). R Sulphuris lactis, 5 iv.; Tineturae saponis viridis, 5 x.; Glycerini, 5 vi.; Spir- itus vini, 3i. M. (Elliot). R Sulphuris lactis, S iss.; Glycerini, 5 i.; Spiritis vini camphorati, 5 x.; Aquas rosae, q.s. M. (Besnier). These various combinations owe their efficacy for the most part to the sulphur they contain, and may be varied according to the physician's wishes. One of the most useful will be found to be: R Zinci sulphatis, potassii sul- phidi, aa gr. xv.; Sulphuris lactis, gr. xx.; Aquas rosae, Si. M. When made with fresh drugs and properly prepared, this lotion is of very great value. It should be applied at night after the face has been thoroughly washed with soap and water, and allowed to remain all night. If irritation is produced, cold cream can be used during the day. It is wise, however, to keep up the effect of the treatment even during the day, and for this purpose a lotion of boric acid can be used or a one- to three-per-cent. solution of resorcin in water, but preferably in alcohol and water, equal parts. A very beneficial lotion is R Acidi borici, gr. xv.; Resorcini, gr. x.; Acidi acetici ililnti, 5 ij; Spiritus vini, 5 vi. M. Potassium sul- phide, o i., in rose water, 5 iv., is also recommended. The mercuric salt is often of value, but it should never be used in conjunction with sulphur prepara- tions, owing to the probable formation of sulphurct of mercury on the surface. Authors recommend P» Hydrargyri bichloridi, gr. xv.; Ammonii chloridi, gr. xxx. to lxx.; Alcoholi, 5 iv.; Aquas, Oi. M. The formula of the "Oriental Lotion" as given by Hebra is: R Hydrargyri bichloridi, 3 i.; Aquae destillatas, 5 iv.; Ovorum iij albumen; Succi citri recentis, oiij-l Sacchari, oi- M. Another formula recommended by the writer is: R Hydrargyri bichloridi, gr. iij. to vi.; Acidi salicylici, gr. xxx.; Acidi acetici diluti, 5 iss.; Spiritus vini, o iiss. M. When using any of these lotions, it should be remembered that more or less desquamation and peeling of the horny layer takes place, and it is advisable to warn patients of the fact. When this occurs, it is wise to discontinue the application and to use an indifferent salve until the reaction has subsided, and then to begin anew with the lotion. Ichthyol as an external agent is most valuable in certain cases. It may be used in watery solution — five to fifty per cent. — or it may be added to any of the foregoing formulae, with the exception of those containing mercuric chloride. The writer has found it of especial benefit in cases in which pustulation was a marked feature; and in full strength or in a fifty- per-cent. dilution it has very commonly served the purpose of aborting a beginning lesion. In those instances of acne in which from time to time one or two papules begin to develop, the ichthyol applica- tion, as mentioned, has been a most valuable agent in cutting short the career of such fresh lesions. In the case of patients in whom there is no complica- tion of a seborrhea oleosa, but who have a natural dryness of the integument, ointments are especially of use. When indicated, they should be such as possess antiseptic properties, and may contain various remedial agents. Among the many recommended, the unguentum hydrargyri ammoniati, five to ten per cent., may be mentioned, and also one made with the red or yellow oxide of mercury — three to ten per cent. A ten-per-cent. sulphur ointment may be of value, or the hypochloride of sulphur may be used — ten to fifteen per cent., or the iodide of sulphur — three to ten per cent. At times the following for- mula will be found a good one: R Unguenti hydrar- gyri oxidi rubri, oij.; Unguenti sulphuris (U. S. P.), 7> iij.; Unguenti aquas rosae, q.s. ad 5i- M. In ordi- nary cases the writer would advise: R Acidi borici, gr. x.; Resorcini, gr. x.; Acidi acetici diluti, o iij- ; Lanolini, ,~vi.; Unguenti aquas rosae, oij. M. In addition to these, there may be mentioned calomel ointment, three to ten per cent., /3-naphthol oint- ment, five per cent., or one containing dermatol, or oxychlorate of bismuth, etc. In cases character- ized by indolence, the unguentum hydrargyri nitratis, diluted (1 to 8, 1 to 4, or 1 to 2), is of benefit. Chrys- arobin, pure carbolic acid, tincture of iodine, have also been used in individual instances with benefit. That is, there is a host of external remedies or "cures" for acne embodied in literature, but when dealing with a case of the disease it should always be kept in mind that each case represents an individual, and whatever line of treatment is instituted it should involve the use of an antiseptic, should be adapted to the peculiarities of each individual patient's skin, and should be adjusted in accordance with the inten- sity of the lesions existing in each case. Vaccine Therapy. — The vaccine therapy of acne has received considerable attention of late and nu- merous articles are to be found in the literature advo- cating its use. At first it was thought necessary to use the opsonic index as a guide to the size of the dose and the frequency of repetition. Experience, how- ever, has shown that the opsonic index is unreliable and impracticable and that the clinical effect upon the patient is the best guide as to the size and frequency of the dose. As a result the use of the opsonic index as a guide in vaccine therapy has been almost uni- versally discontinued. Stoner in 1911 collected 139 cases of acne from the literature which had been treated by bacterial injections. Practically all had received injections of Staphylococcus albus alone. Of these 139 cases seventy-nine were reported as cured, forty-eight as improved, nine as not bene- fited, seven had discontinued treatment, and one was still under treatment. Gilchrist considers that Staphylococcus albus vac- cine is very helpful in cases of acne of the superficial pustular type, that is, when the Staphylococcus albus as a secondary invader predominates. Engman considers that albus vaccine alone is of little value in the treatment of acne vulgaris. He, in fact, rarely uses it as he looks upon the Staphylococcus albus as a secondary factor of no therapeutic impor- tance. Fleming in 1909 was the first to present any convincing demonstration of the use of acne bacillus vaccine. He treated three cases with a mixed vac- cine of Staphylococcus albus and Bacillus acnes, Fleming claimed that while the staphylococci are always associated with the pustular lesions of acne, the acne bacillus is the true etiological factor and, in order to produce an immunity to the disease, vaccines of both organisms must be used. Engman claims that treatment with acne bacillus vaccine, provided a proper technique is adopted, yields most brilliant results. He considers that indifferent results are the fault of the technique and not the fault of the method. He recommends small doses sufficient to cause a short negative phase. His initial dose is three to five million and he rarely finds it necessary to give as high as seven to ten million. The dose is repeated at five- to seven-day intervals and the treatment is supplemented by means to produce local hyperemia, thus bringing an increased quantity of immune serum to the part. He finds stock vaccines very reliable and can be used in most instances. Gilchrist recom- mends an initial dose of five million of the Bacillus acnes, and increases gradually each week to thirty million unless the negative phase becomes pronounced., which indicates that too much vaccine is being given. He uses the Bacillus acnes vaccine alone, unless the secondary invader predominates markedly. King- Smith found in cases due to the acne bacillus that treatment with Bacillus acnes vaccine alone was rather disappointing; in cases where the acne bacillus and Staphylococcus albus were both present in large numbers treatment with vaccines made from these organisms gave good results — at least fifty per cent, showed marked improvement; in cases in which 86 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \t nc Necrotica Staphylococcus albus alone was found the correspond- ing vaccine gave excellent results. Lovejoy reports fifty cases treated with acne bacillus and a polyvalent staphylococcus vaccine with very satisfactory results. He gave from three to five million of the acne bacillus at a dose and from 150 to 2.30 million of the staphy- lococcus vaccine. Stock vaccines seemed to give as good results as autogenous. Smiley treated 100 eases of acne vulgaris with autogenous mixed vaccines with such uniformly good results that when one can control the patient a cure of the condition can be promised in every case. The associated symptoms, such as headache, constipation, anemia, mental and phvsical lassitude, etc., were greatly modified or entirely disappeared in those patients thus treated. In consequence Smiley believes with Gilchrist, that the acne bacillus or its toxins are responsible for the associated symptoms and conditions occurring in acne infections. Treatment with a stock vaccine was not satisfactory in regard to clearing up the sequel* or complications. It will be seen from the foregoing that the more recent workers are unanimous in reporting beneficial results in the treatment of acne vulgaris with Bacillus acnes vaccine. They all recommend small increasing • repeated at a five- to seven-day interval. The initial dose is usually three to five million and only Gilchrist finds it necessary to increase beyond ten million at a dose. He occasionally gives thirty million. Opinions vary as to the value of staphy- lococcus vaccine in the treatment of acne vulgaris. Most reports show that it is of benefit only in the dis- tinctly pustular cases. The writer cannot agree with the opinion of Gil- christ and Smiley that the headache, anemia, con- stipation, etc., so often associated with acne are due to the absorption of the toxins of Bacillus arms from the local lesions. If these symptoms are treated with appropriate remedies as outlined when dis- cussing the internal treatment he thinks the possibil- ities of success will be much greater than if vaccine treatment alone is relied upon. X-ray Treatment. — Many authorities claim that the most rapidly effective local treatment for acne is found in the skilful use of the z-rays. Recurrences are said to happen less often. Many cases, however, can be managed just as well without it and it would seem best to reserve its use for persistent rebellious cases, especially of the indurated type. The use of such a powerful and at times dangerous remedy as z-rays for such a simple condition as acne, which can usually be successfully treated by other simple and perfectly safe methods, seems unjustifiable. More- over, when relapses occur they are much more rebel- lious to x-ray or any other form of treatment. If used at all its use should be limited to acne indurata of the back and shoulders. Frequently one sees the development of an atrophic wrinkled skin with tel- angiectases even under the most careful use of the x-rays, and this condition would of course be of less moment on the back than on the face. It is not necessary to produce a dermatitis to get good results. In fact, it is better if possible to attempt to get the curative effects without producing the slightest erythema as in this way the possibility of producing future atrophy is much lessened. The exposures should always be made most carefully. A soft to medium tube should be used at ten to fifteen inches distance and for three to four minutes duration twice weekly. If improvement is shown it is best to adhere to such cautious technique. Geoege T. Elliot. Acne Necrotica. — Si/nonyms: Acne frontalis, seu varioliformis; acne pilaris; acne rodens; acne atro- phica; folliculitis varioliformis, etc. Perhaps no affec- tion has so many different designations in actual daily use. It is very desirable that some term acceptable to dermatologists of all countries be selected by agreement, for our knowledge of this disease cannot but be retarded by this lack of consensus. At present the tendency appears to be toward the use of the terms acne varioliformis, and folliculitis varioli- formis despite the fact that some of the others are more logical. Definition. — A chronic, recurrent, papulo-pustular affection, having its seat about the hair follicles, lead- ing to necrosis of the involved tissues and terminating in a variola-like scar. Symptomatology. — The site of predilection is the forehead, at the margin of the hair, and it is this fact which gave rise to the name acne frontalis. A wider acquaintance with the affection, however, has shown that it involves other regions. It may extend to the hairy scalp, the face, the neck, and the interscapular and intermammary regions. Cases of more or less generalized eruptions of papulo-pustules terminating in necrosis and scar formation have been described, which present many of the clinical features of this malady. The primary lesion is generally stated to be a papule which soon becomes encrusted and covers an underlying ulceration. Sabouraud describes the elementary lesion as an umbilicated vesicle always seated about a hair. Within two or three days it attains its full dimensions, about three millimeters in diameter. Its central portion then sinks below the level of the surrounding integument, becomes harder, encrusted, and gives to the observer the impression that it is mortised into the skin. The color of the crust, at first a yellow or brownish yellow, darkens with age. The lesion may remain in this state for several weeks; exceptionally two or more pustules may become confluent. On removing the crust or after its spontaneous separation, a red, moist, or dry depression is left which eventually because white like the variola scar. Superficial lesions healing with shallow depressions, and deeper ones leading to depressed scars, are generally encountered in every case (Unna). The presence of lesions in various stages of evolu- tion, with pigmented and non-pigmented scars of older ones, makes up the peculiar clinical picture of the disease. Pathology and Morbid Anatomy. — It is now gen- erally conceded that acne necrotica is a perifolliculitis probably of locally infectious origin. Sabouraud insists that the affection demands for its development hair follicles previously infected with his microbacillus of fatty seborrhea. It is not possible to have acne necrotica, according to this writer, unless these infected follicles are invaded by the yellow staphylococci which are the essential agents in producing the disease. The infection takes place at the follicular opening, and from this point invades the epidermis in a circular manner, giving rise, as the process increases, to an intense leucoeytosis in the papillary and subpapillary dermal regions. The final stage is characterized by a dry necrosis of all the involved tissues. Sabouraud w T as unable to differentiate the yellow staphylococcus, which he found in all lesions of acne necrotica, from ordinary Staphylococcus aureus from other sources. The distinct clinical lesion to which it is supposed here to give rise may be due to the previous damage to the follicle by the microbacillus of seborrhea, to its admixture with this organism, to a change in the virulency of the staphylococcus, or to other causes which we are at present unable to determine. Microorganisms had been previously described in these lesions by Touton, Unna, myself, and others. Touton was not inclined to attribute to them any pathogenic importance. Unna, however, considers the affection due to a mixed infection with a small bacillus and his diplococci of seborrhoic eczema. In lesions examined by myself, staphylococci 87 Acne Necrotlca REFERENCE HANDBOOK OF THE MEDICAL SCIENCES were found which are probably identical with those described by Sabouraud. In substance it may be stated that acne variolifor- mis (Hebra) is an inflammation of the pilo-sebaceous system, probably microbic in origin, leading to destruction of these organs and the surrounding derma, and that Bazin was correct in naming the disease acne pilaris. Etiology. — Acne necrotica is essentially a disease of adult life. It is rarely seen before the age of thirty, and may develop late in life. Men are more frequently affected than women. Some of the older dermatological writers attributed it to syphilis. Although sometimes mistaken for a grouped papulo-pustular syphilide on the forehead or at the sites of acne necrotica, it does not owe its existence to that infection. Its more frequent occurrence among those in the low T er walks of life, and its location in the majority of instances on the forehead, exposed to the pressure of unclean hat bands, lend weight to the theory of local infection. A pre-existing fatty seborrhea is, according to Sabouraud, an absolutely essential condition for the development of an acne necrotica by affording a locus minoris resistentitc, and determining the clinical features of the eruption. Diagnosis. — The absence of comedones and the sites affected, together with the depressed encrusted lesions, intermingled with white and pigmented scars, easily enables one to differentiate this variety of folliculitis from acne vulgaris. Its differential diagnosis from a papulo-pustular or a grouped pustulo- tubercular syphilide is more difficult. The history of frequent recurrences extending over months or years, which patients with acne necrotica give us, together with the absence of concomitant manifesta- tions of syphilis, should enable one to separate the two diseases. Syphilis again shows no predilection for the hairy parts of the face which the former affec- tion does in a striking manner. Other varieties of pustular affections of the follicles do not give rise to the peculiar and rapid tissue necrosis with its resulting variola-like scar. It is questionable whether the generalized eruption of papulo-pustules resulting in scar formation like that of acne necrotica of the face should be included with this disease in a single group. This disseminated eruption, to which various names have been given, as hydradenitis suppurativa, acnitis, necrotizing granuloma, etc., frequently begins as a deep-seated papule about the coil glands or in the con- nective tissue of the derma independently of the gland- ular structures. While the two diseases present many similar clinical features, it is quite probable that they depend on different infectious agents. Boeck claims for the generalized eruption a close relationship with lupus erythematosus, and believes that both affections are due to the toxic products of the tubercle bacillus ab- sorbed from a focus in some part of the body. Prognosis. — It is not difficult to cure a single attack of the eruption, but recurrences are the rule. and we have no certain means of preventing them or of limiting their frequency. Treatment. — The various internal remedies recom- mended by dermatological writers have probably no value in curing the attacks or preventing relapses. The lesions are quite readily healed by ointments containing sulphur, resorcin, /3 naphthol, salicylic acid, ammoniated mercury, or calomel. These drugs may be used in the strength of two to five per cent, or stronger. Careful attention should be paid to the h}'giene of the scalp and to personal cleanliness, as the agent pro- ducing the infection is probably widely scattered. The scalp should be frequently washed with the ordinary tincture of green soap, followed by lotions containing bichloride of mercury, 1:1,000, to insure its disinfection. Resorcin lotions (two to ten per 88 cent, in alcohol and water, equal parts), with the occasional use of sulphur or salicylic-acid ointment, may be used alternately with the bichloride lotion. It is only by the persistent use of local antiseptic applications, not only to the eruption itself, but to the surrounding skin, that we may hope to prevent or delay relapses. J. A. Fordyce. Literature. Pick: Archiv f. Dermat. u. Syph., p. 551, 1SS9. Touton: Verhand. der Deutsch. dermatol. Gesellschaft. Zweiter u. Drifter Congress, p. 2S7, 1S92. Unna: Histopathology of Skin Diseases; English translation, p. 366. Fordyce: Journal of Cutaneous and Genito-Urinary Diseases, voL xii., p. 152. 1S94. Sabouraud: Ann. de derinat. et de syph., tome x., p. 841, 1899. Acne Rosacea. — Synonyms: Acne erythematosa, gutta rosacea; acn6 rosee; Couperose; Kupfernase. Definition. — Acne rosacea represents not one disease, but a rosacea with a superimposed acne. Rosacea is a congestive disturbance affecting the nose and portions of the face, transitory at first, but after- ward becoming permanent, and represented by red- ness, dilatation of the cutaneous blood-vessels, the formation of a telangiectasis, and in some instances by more or less hypertrophy of the connective tissue Fig. 20. — Acne Rosacea. Showing Dilated Blood-vessels. (Author's drawing.) and the glandular elements of the skin. The acne lesions developing in the course of the process are secondary products, and are expressions of an inflam- matory process affecting the sebaceous glands. Symptomatology. — Rosacea attacks especially the nose and the neighboring portions of the cheeks, though it may extend laterally to the malar prominences, or even implicate the forehead and the chin, and in some eases the entire face, with the exception of the orbital spaces. The symptoms characterizing the process vary in degree and in intensity according to the stage and the grade of the affection. In the earlier stages, there is only more or less marked hyperemia or congestion of the nose and cheeks, occurring after eating or drinking, or after exposure to cold, or at the time of menstruation. The symp- toms are usually transitory, and, remaining in exis- tence for a short space of time, disappear without leaving a trace. The patients generally complain that there is at the time a sensation of heat or of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acne Rosacea burning, but yet the skin itself is cold to the touch. This recurrent congestion may take place for a variable length of time, alternating with a return to normal conditions; but sooner or later the hyperemia occurs more often and apparently without cause or induce- ment, and gradually the redness becomes a stable and permanent fact, varying only in degree from time to time. The congestive disturbance, when permanent, is diffuse and sluggish in character, with- out definite outlines, and the redness returns only slowly after pressure. At times, however, it may be active and may simulate an erysipelas or acute der- matitis. When exposed to the cold, the affected surfaces are liable to become bluish and cyanotic in appearance. The stage of permanent congestion may persist for a variable length of time without any further change occurring in the skin. But sooner or later there develops upon the nose and other surfaces a condition of telangiectasia, represented by fine, tortuous, dilated blood-vessels. These vary in size, being usually more prominent and larger on the alae nasi, and they sometimes present in their course dis- tinct varicosities. The telangiectatic condition may be slight or severe, and in some cases attains such a height that the entire nose and cheeks are covered with distinctly evident tortuous vascular dilata- tions, varying in color from bright red to purplish red, according to the temperature and the somatic condition of the affected individual. The process, as a rule, does not progress beyond this stage, but occasionally and after long existence, a fibriod degeneration of the surface attacked takes place. It is the nose, however, which, as a rule, is the seat of this change, the other portions of the face being affected only to a slight degree and moderately thick- ened. The nose under these conditions becomes hyper- trophied as a whole, and on portions of its superficies there may in addition arise lobulated or peduncu- lated, firm growths of various sizes, which sometimes attain enormous development (rhinophyma). In all of the stages of rosacea a seborrhea oleosa generally coexists. The affected surface is greasy, the orifices of the sebaceous glands are dilated, and minute drops of oil can be seen exuding from them after the flushing has subsided, and even independ- ently of the hyperemia. When the congestion has become permanent, these orifices may be so exces- sively dilated that the skin has a sieve-like appearance, but it is in the hypertrophic form of rosacea that the greatest degree of dilatation is found. In other eases, the affected surface is scaly and dry or covered with small, thin, yellowish scales, or with larger greasy, soft crusts. The patients complain of itching and burning, and these symptoms are invariably associated with a yellow, scaly discoloration of the interpalpebral space and with a certain grade of what is generally called pityriasis, or seborrhea sicca capi- tis. The clinical picture presented by these cases is quite distinct from that of the others described and represents a complication of rosacea and dermatitis seborrhoica. In fact, the presence of the latter process alone may and frequently does lead to the same congestive and hyperemic objective appearances as originate from other and different internal causes. A further and very common complication of a rosacea is acne, which, in the majority of cases, sooner or later arises on the congested surface. It is when the two processes are combined that an acne rosa- cea may be said to exist. The lesions may be either of the superficial (simplex) variety or of the deeper (indurata), or both may be present. They will be found on the nose and cheeks, singly or very numerous, and occurring in numbers on the nose, in which organ they frequently cause considerable defor- mity and also very marked pain. In themselves, the lesions differ in no wise from those others which occur independently of rosacea. The course of the process is always a slow one. and, having developed, it persists in varying degree for an indefinite period of time, or until its inducing cause or causes have been removed by appropriate cure or treatment. Slight subsidences of the congestive disturbance and of the acne lesions are generally seen to alternate with exacerbations. Pathology and Morbid Anatomy. — Rosacea is primarily a vasomotor neurosis, resulting in retarda- tion of the circulation in the superficial capillary plexus. Although at first transitory, this paretic condition of the blood-vessels becomes, through fre- quent repetition, somewhat fixed. In consequence the congestive redness becomes permanently estab- lished, and the telangiectases and varicosities gradu- ally become evident. The implication of the blood- vessels is not limited to the superficial ones, but may extend to the deeper plexus, and so all the vessels throughout the skin may be affected. In conse- quence of the congestion, the sebaceous glands are influenced and the seborrhea oleosa arises. The acne lesions owe their origin to the resulting debased nutrition of the skin. In some cases new connective tissue forms about the blood-vessels and the folli- cles, thus producing a thickening of the corium and causing ultimately either the hypertrophic form of the disease, or, in very severe cases, rhinophyma. On the other hand, one form of the hypertrophic stage is attributed to an increase in size of the sebaceous follicles. The histological anatomy of the first stage of rosa- cea has been found by the writer to be represented by a dilatation of the blood-vessels in the upper portion of the cutis and by a few collections of round cells about them. In the second stage, there was an increase in degree in these features, many dilated vessels having thin walls, and large lumina being found widely distributed throughout the corium, which was also slightly thickened and edematous. In the third stage (rhinophyma), marked hyper- plasia of the connective-tissue elements of the skin had taken place, and the sebaceous glands were also somewhat enlarged. The blood-vessels were large and tortuous and their coats were thickened. Sub- stantially the same changes have been found by others, but Unna also ascribes the formation of the growths in some cases to an enlargement and multiplication of the sebaceous glands, which thus constitute the major part of the rhinophymatous change. In other cases he states that the connective-tissue hypertrophy predominates, though the glandular change may also be a prominent feature. The investigations of Hans Hebra led to practically the same conclusions. The histopathology of the acne lesions occurring in connection with rosacea does not differ from that of the same efflorescences wdiich arise independently. Etiology". — Rosacea develops more frequently in women than in men, and while occurring especially after the age of thirty and in older people, yet it also is not infrequently seen in younger persons. It arises in women very commonly in association with pu- berty, with menstrual and utero-ovarian irritation, and especially at the menopause. It also is liable to appear during pregnancy, in sterile women, and very frequently among those others who come in the cate- gory of old maids. In both sexes, disorders of the gastrointestinal canal are potent factors in the pro- duction of the congestive disturbance, and in indi- vidual cases there will therefore be found such dis- turbances as constipation, gastric or intestinal indiges- tion, fermentative processes, etc. Anemia is often the basis of the cutaneous disease, and so also is plethora. The gouty and rheumatic diatheses are prone to favor the development of the disease both directly and through those functional and other dis- turbances which are so liable to occur in those who are subjects of these constitutional conditions. Sed- entary habits strongly predispose to the process, and 89 Acne Rosacea REFERENCE HANDBOOK OF THE MEDICAL SCIENCES hence rosacea and its accompanying feature, acne, very commonly affect seamstresses, sewing girls, and others obliged by their occupation to forego outdoor or physical exercise. In connection, however, with their confining occupations, it should also be mentioned that these same individuals are usually subjects of func- tional bodily disturbances, due to their diet and poor hygiene. The morphine habit has been claimed to produce the disease, and it has also been attributed to various intranasal processes, such as atrophic and hypertrophic rhinitis, chronic catarrhal inflammations of various degrees, and sycosis of the vibrissa. Seb- orrheic dermatitis is claimed by Unna to be a most important cause of rosacea in women. It would be more correct, however, to regard its effects when located on the nose as in the line of producing a red- ness similar to rosacea, through the inflammatory congestion incident to its presence, than to claim that it causes that latter disease itself. Exposure to cold and bad weather is an external factor in the etiology of the process. The writer has seen sun- burn determine its existence, and in a number of cases a slight chilblain condition of the nose led to objective symptoms simulating accurately a mild rosacea. Face steaming, use of very hot water, con- tinual exposure to the heat of a fire — all enter into this category. The effect of diet and abuse of spir- ituous liquors is generally very well known. The articles of diet which are injurious are practically the same as have been mentioned for acne, and their effects are not so much in themselves, as in the gastro- intestinal and other disturbances which they may bring about. When used in excess, all liquors may lead to the development of a rosacea, but the most pernicious are fermented drinks, such as ale, beer, porter, and also sweet wines and liquors, port, etc. Tea, when improperly used, may have a similar influence, owing to the injurious effect of the tannin on the gastrointestinal canal. The influence of smok- ing in itself is certainly remote, though it possibly may indirectly operate through the production of a catarrhal or other intranasal irritation. In many cases, however, no definite etiological cause can be discovered. Diagnosis. — The diagnosis of rosacea will be obtained from the history of its development, as well as from the clinical symptoms presented by it. As the disease occupies, as a rule, the nose and neighbor- ing portions of the cheeks, it will be found that the persistent redness was preceded by intermittent flushing, and was followed by superficial capillary dilatation and the formation of telangiectases and varicosites. Lupus erythematosus, which commonly occupies the same surfaces, may be differen- tiated from a rosacea by the distinct delimitation of the patches constituting it. The outlines, though irregular, are sharply defined, the edges are usually elevated and enclose a scaly area. The patches tend to enlarge by peripheral extension, and as a rule atrophic changes occur over the affected area. Erythematous eczema should also be differentiated from rosacea. It occurrence is not limited, however, to the same localities, but it appears anywhere on the face, or neck, or- other surface. It appears bruskly as an acute process, which in time may become chronic in character. The affected portions are some- what swollen from serous exudation; they are scaly and rough to the touch, or have a glazed, varnished appearance, and there is much burning and itching. When syphilis exists on the nose, either in the form of the papulo-pustular grouped syphilide or when there are cutaneous gummata, errors in diagnosis are not only possible, but are not infrequent. If attention, however, is paid to the history of the development of the redness and of the lesions dis- cretely located or aggregated together in groups upon it; if it is noted that beneath the crusts distinct ulcer- ation with subsequent scarring occurs, and that there is a tendency as regards the gummatous lesions to serpiginous extension with consecutive cicatrization, then the diagnostic difficulty should give no trouble. The term erysipelas is used very loosely both by medical men and by patients, and it is a most common fact to hear the latter complain of an erysipelas, which in reality is a rosacea of several months' or years' standing. They often state that their diagnosis was that made by their physician. It should, how- ever, be remembered that, though erysipelas does frequently affect the nose primarily, yet it is an acute process,, begins with slight or marked chills, and is accompanied by elevation of temperature and such other somatic disturbances as are never associated with a rosacea. Prognosis. — The prognosis of this cutaneous affection will depend to a great extent upon the possi- bility of removing its inducing cause or causes in any given case and upon the ability to prevent their recurrence. An entire and absolute cure is obtain- able and can be effected, or if not this much, at any rate a most decided amelioration of the symptoms. Treatment. — In the treatment of rosacea or acne rosacea, very much the same procedures are called for as have been detailed for acne simplex and acne indurata. The cases require both internal and external care, the former being such as will remove or modify that defect in functional or physical health which may be found in the case under consideration at the time, and the latter being such as will bring back tone and vasomotor control to the paretic blood-ves- sels, or will destroy them, or, in the severest grades of the disease, will remove the disfiguring growths which have arisen. In general it may be said that all inter- nal medication should be such as will correct the exist- ing constipation or gastrointestinal disturbance present in the case. If uterine or ovarian irritation exists, it should be attended to; and also gout, rheuma- tism, and lithemic conditions should receive proper attention. Anemia or plethora, the tuberculous diathesis, and every other factor should be properly estimated and seen to, and all matters pertaining to errors of diet should be diligently investigated. As a rule, cheese, oatmeal, sweets, pastries, nuts, ferment- able articles, and such as are highly seasoned, stimu- lating, and liable to tax the digestive powers, should be forbidden. Beer and alcohol and all sweet bever- ages should be stopped, though a light claret with water or a dry Moselle wine may be allowed at meals. Coffee without milk is perfectly allowable, but tea should be cut off, unless it is very weak and freshly made. With these exceptions, the diet should be of a simple, easily digested, and nutritious character. The needs and digestive capabilities of each patient should be studied, and the food taken should be such as is found appropriate. So far as drugs are concerned, it may be stated that in many of the cases in which the process is in its inception, in which the redness has not become persistent, but is represented by periods of flushing and of retrogression, the mineral acids are particularly useful. Especially is this the case with the dilute nitric, muriatic, or nitromuriatic acid. Another class, however, may require alkaline remedies and diuretics, the citrate and acetate of potassium, or some of the more recent ones, uricedin, urotropin, aspirin, etc., or it may be saline purgatives that are called for. By means of these it is possible, in the early cases, to divert the blood current from the face to some other part of the body. When the congestive disturbance of the nose and face has become a stable fact, then a very useful remedy is ichthyol. Begin- ing with doses of gr. v., it should be increased until gr. xv. are taken t.i.d. It may be given in pill or capsule form, or simply diluted with water or coffee. Toler- ance to its peculiar taste is quickly established, and only rarely have I found the remedy to be objection- 90 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aconite able or distressing to the patient. Resides these particular remedies — and they should be given in conjunction with those others demanded by the necessities of the individual case — ergot and ergotin have been recommended, as well as belladonna, digitalis, quinine, codliver oil, etc. But all of these are intended to meet indications furnished by certain cases, and should not be regarded as of general or extended value. Arsenic may be said to be al\v:i\ - injurious in rosacea. The local treatment is of the utmost importance, and some, if not many, instances of the disease may be relieved by it alone. In acute cases, characterized by active hyperemia and burning, soothing applications are to be used. The magnesium carbonate and zinc oxide, or the calamine and zinc lotin referred to in the article on Acne, is indicated; or a lotion of R Bismuthi subnitratis, gr. xxx.; Bismuthi oxychloratis, gr. xl. ; Magnesia? carbonatis, gr. xx. ; Aqua; rosa;, 5 i., or the Liquor soda;, chlorinata;, diluted 1 :20, or less, or more, may be applied. A very thin boiled starch poultice is frequently of great value, as is also the official liquor calcis. The majority of the cases of rosacea coming under treatment are, however, of the chronic type, have passed beyond the primary stage, and require a very different order of local treatment — one which is stimulating in its effects and which is intended to improve the vasomotor tone of the paretic vessels. For this purpose, stronger applications than are needed in acne in general are called for, and a stiff paste is often useful — R Resorcin, gr. 1. to cl.; Kaolin, zinci oxidi, aa 5 ij.; Unguent, aqua? rosa;, g i. M. In place of the resorcin, ichthyol may be substituted in the strength of ten to fifty per cent., or the ichthyol may be used pure. The pastes are applied every night until a decided reaction has been produced and the horny layer has a glazed appearance and is beginning to exfoliate. The paste used should then be replaced by a mild, soothing ointment, R Acidi salicylici, gr. x.; Zinci oxidi. '.) ij.; Unguent, aqua; rosa;, o i-J or an > r other similar salve. When the exfoliation has ceased, the surface will be found much improved in all probability, and the same paste, or a weaker one, may again be applied and the same course followed. This procedure may be kept up until all the redness has disappeared, or toward the end the lotion given under Acne — R Zinci sulphatis, Potassii sulphidi, aa. 5 ss.; Sulphuris lactis, 5 i-,' Aqua; rosa;, o i- — may be applied. To obtain the same result, caustic potash solutions (two to ten per cent.) have been recommended, or vigorous washing with green soap. Likewise Vleminckx's solution in full strength or diluted one-half, or even weaker, is at times ot benefit. Chrysarobin has been advised and used, but the danger of conjunctivitis from its appli- cation on the face renders it of doubtful service. When seborrhoic dermatitis is the cause of the rosacea, resorcin and sulphur are particularly called for. They may be used either in ointment form or in water, or in alcohol and water, equal parts. The acne lesions which may be coincident with the rosacea do not require any special treatment, but the telangiectasia and dilated blood-vessels remaining after subsidence of the congestive disturbance have to be dealt with. They may be destroyed by multiple scarification, care being taken to split the vessel longitudinally with a fine-pointed knife and then to make transverse incisions. It has been recommended to touch the open vessel along its length with nitrate of silver, but that usually leaves a scar as a result. Iodine and pure carbolic acid have also been advised, but when the scarification has been properly done, none of these measures is necessary. Excellent results are obtained from electrolysis, and also from the use of the thermocautery. As regards the former, the needle used for electrolytic destruction of super- fluous hair is all that is necessary. The needle at- tached to the negative pole of a galvanic battery should penetrate the vessel before the circuit is closed — that is, before the electric current is turned on. The positive pole — sponge moistened with water or salt solution — is grasped by the patient after the needle has been introduced into the vessel. The procedure IS very painful and requires much time, and scarring is very liable to result. The thermocautery acts on the same principle, but it is neither as painful nor as liable to cause scars. A needle point should be used, such as is furnished with the Mikrobrenner introduced into practice by Unna of Hamburg. Much the same result may, however, be obtained if an ordinary sewing needle grasped by a needle holder be heated in an alcohol flame and made use of to puncture the dilated blood-vessels in their course. The method is simple, and I have found it absolutely as efficacious as the more showy and impressive ones previously mentioned. When the case is one of hypertrophic rosacea, in which the development of connective-tissue growths in greater or lesser degree has occurred, surgical interference is called for. Ablation of the excrescences is necessary and may be done with the knife or the galvanocautery. Electrolysis has been recommended, but is of uncertain value, if not entirely without result. For a discussion of the value of vaccine and i-ray treatment the reader is referred to the article on acne where these questions are taken up fully. In acne, rosacea Staphylococcus albus vaccine is more generally called for, as the lesions are more usually of the pustular type. George T. Elliot. Acoin. — A synthetic hydrochloride of dipara- anisylmonophenethyl-guanidine, introduced by Trolldenier, in ls.99, as a safe and efficient local anesthetic substitute for cocaine. It occurs as a white crystalline powder, soluble in about fifteen parts of water. Instilled into the conjunctiva it produces anesthesia without increasing intraocular pressure or exerting any cycloplegic effect, but is somewhat irritating and is therefore not recommended when inflammation is present. It is said to be free from the systemic effects of cocaine. It is also used in one per cent, solution for subconjunctival injection, in which use it is less painful than cocaine. It is recommended in 1-1000 solution in physiological salt solution for the production of infiltration anes- thesia by the Schleich method. In one-per-cent. solution it has been employed as a local anesthetic in dentistry. Aconite, Aconittjm. — (Monkshood, Wolfsbane.) "The dried tuberous root of Aeon Hum Napellus L. (fam. Ranunculacece) collected in autumn; yielding, when assayed by the process given below, not less than 0.5 per cent, of aconitine." (IT. S. P.) This definition will probably be amended in the forthcom- ing revision by omitting the requirement of autumn collection, and permitting a short piece of the stem- base to be attached to the tuber. Aconitum L. is a genus of some sixty species, dis- tributed almost throughout the Northern hemisphere. Many of the species resemble one another so closely that even from the examination of complete speci- mens, with flower and fruit, botanists have reached diverse conclusions regarding their identity or dis- tinctness. It is therefore not remarkable that the detached medicinal portions should be found difficult of differentiation, or that various species should have been found mixed in commerce. As the chemical and medicinal properties of the different species vary greatly in degree, the tubers of at least one species being used for food, these mixtures become serious in the case of such an important drug. Of late, much more care has been exercised than formerly, so that this adulteration, intentional or accidental, has be- come infrequent. Partly because of this element, and 91 Aconite REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ■ r f f ^i Y p. partly because experiment has proven the activity of the drug to increase under cultivation, the British Pharmacopoeia now requires that only the cultivated English tuber shall be supplied. It is also cultivated in various continental localities. These cultivated products are much more expensive than the ordinary drug, but their specification appears fully justified, except when a standardized drug or preparation (see Constituents) is employed. The official species occurs abundantly in the moun- tainous districts of Central Europe, extending up the mountain sides to a very high elevation, as well as deep into the valleys. The plant is cultivated as an ornamental flower in the United States, where occa- sionally it escapes. The tubers used in medicine are collected in Europe. Since the herb, although unofficial, is much used in medicine, the entire plant is here described. The simple, stiff, upright stem of aconite rises from 50 to 100 cm. (20 to 40 inches) from the ground, bearing numerous alternate leaves, and a long, close, terminal, spike-like, raceme (Fig. 21). The leaves are sub- rotund, from 5 to 20 cm. in diameter (2 to 8 inches), rather stiff and thick, smooth, shining, and dark Fig. 21. — Aconitum napellus L. green above and paler be- low. The blade is pal- mately three-parted; the lateral segments are again divided nearly to the base. The narrowly wedge- shaped divisions are further three or two lobed, and these lobes are again incised, or cleft, with linear and pointed tips. The leaves become less compound toward the upper part of the stem, and are finally reduced to three- or several-cleft bracts. They have no marked odor, but upon being chewed produce, like the tuber, a persistent stinging sensation in the mouth. They are poisonous and contain a small and uncertain amount of aconitine and considerable aconitic arid, the latter of no therapeutic importance. The flowers are of striking appearance; the corolla is nearly want- ing, and its place is taken by a large colored calyx, of which the upper sepal is developed into a deep cup- shaped helmet, that sits upon the rest of the flower like a bonnet (Fig. 22). The pistils are three, containing numerous small ovules. The form of the mature tuber gives the specific name to the plant (napellus, a little turnip). It is a simple, conical, tapering tuber, ending in a long, slender, cylindrical tap-root, and bearing numerous rootlets upon its sides (see Fig. 23). From its scaly crown arises the flowering stem, and at the base of this stem a short stolon extends horizontally under the ground, and bears on its extremity a young tuber, more or less developed according to the season, and destined to produce the plant of the succeeding year. There may also remain upon the other side of the crown a similar but dead connection between the present tuber and the remains of that of the preceding year. This habit of growth well enables us to determine the sea- sun when the tuber was collected. When it shall be- come positively determined at what season it is most Fig. 22. — Entire Flower of Aconitum napellus. active, this knowledge will doubtless prove of the greatest value to us. Fresh aconite tuber is brown externally, white within, and has a biting benumbing "taste," which has caused it to be occasionally stupidly mistaken for horseradish. The dried tuber, which constitutes the usual drug {Aconitum, U. S. P.; Aconiti Radix, B. P.; Tubera Aetiniti, P. G.; Racine d'aconit impel, Codex Med., etc.), is from 1 to 2 cm. in diameter at the base, and from 5 to 7 cm. in length (two-fifths to four-fifths inch, by 2 to 3 inches) ; more or less shrivelled and wrinkled longitudinally especially below; often curved and twisted, or broken. The external color is dark brown; internally it is grayish, showing, after being soaked up, in a transverse section, a distinct, five to eight pointed stellate cambium ring, in each angle of which is a well-developed fibrovascular bundle. Fre- quently the tubers are attached in pairs; when not, the scar where they were broken apart can be seen. The taste is similar to that of the fresh root, but the stinging sensation may be a little de- layed. Spanish aco- nite is large, stout, and of a light dirty- brown color. It is usually deficient in strength. Aconite, even when coming solely from Aconitum napellus, is variable in quality. The age of the root has much to do with this. Grown in differ- ent countries, or un- der varying circum- stances, it is subject to considerable varia- \ tion in quality. Composition. — Its active constituent is the alkaloid Aconi- tine, described below. The determination of its aconitine percent- age therefore constitutes a perfect method of esti- mating its quality. Owing to difficulties in its extrac- tion, this determination was formerly impracticable, but a reliable method of assay is now given in the Pharmacopoeia. It has also been proposed to deter- mine the presence of the normal percentage of alka- loid by securing the tingling effect upon the tongue and lips by the use of a solution of a specific degree of dilution; but the personal equation is so great, and the effects of training so important, that this method has not found favor. The amount of aconitine, in a first-class sample, will be about seven one-hundredths of one per cent. In addition to the aconitine, there is a small quantity of picraconitine or isaconitine. Besides the alkaloid, a large amount of aconitic acid, combined with calcium, is present. Resin and slight amounts of fat and sugar are also found. The aconites were known to the ancients, both in Europe and Asia, as poisons, and are said to be still used by some of the hill tribes of India to envenom their arrows. They were employed as medicines in Germany in the twelfth, and on the islands of Great Britain in the thirteenth centuries, but after- ward fell into disuse until 1762, when Stoerck of Vienna again introduced them to the medical pro- fession, since which time they have been constantly used. Physiological Action. — There is nothing in the Fig. 23. — Tubers and Roots of Aconitum napellus. 92 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES AronlCic Acid composition of aconite which materially modifies the action of the aconitine. Primary Effects. — It sharply stimulates certain of the nerve endings on coming into contact with them, as well as certain of the encephalic centers. These effects upon the nerve endings are evidenced by a tingling sensation in the skin, whether the aconite be directly applied or be carried there in the circulation. A similar tingling is produced upon contact with the mucous membrane, ami this becomes a severe irrita- tion when the drug is applied in concentrated form, as when the dust of the alkaloid is inhaled or reaches tin- eyes. This effect of aconite upon the mouth is markedly to increase the salivary and mucous secre- tion. It produces some increase of perspiration in the same directly stimulating manner on being carried to the skin. Under careful observation, spasmodic contractions of voluntary muscular fiber can be seen, while stimulation of the vasomotor mechanism (whether central or peripheral is not certainly known) results in arterial constriction, when other and antago- nistic influences resulting from the drug's action are excluded. At the same time, the pupil is temporarily contracted. Under the same conditions of control, increased cardiac action is observed. A slight diu- retic effect, in spite of decreased blood-pressure, is probably due to direct renal stimulation. Stimu- lation of the medullary centers is plainly evidenced by the strong cardiac inhibitory action which is the most prominent effect of the drug, and by convulsions, which in poisoning often occur before the respiration has failed sufficiently to produce them. There is a powerful stimulation of the respiratory center, though the action is temporary, irregular, and spas- modic. The vomiting which is often present may also be due in part to the same central stimulating cause. When nausea is present, the diaphoresis is increased. The powerful action on the vagus results in a marked slowing of the heart, and as the systole is much the more abbreviated, the heart is weak as well as slow, and blood-pressure is reduced. The tempera- ture falls, partly owing to this cause, partly to the perspiration, and, some think, partly by reason of the disturbance of the heat centers. Secondary Effects. — The secondary effect of aconite i- to paralyze the parts at first stimulated, though these are affected in very different degrees as to both strength and promptness. Failure of the sensory nerve endings produces anesthesia where tingling before existed, so that a sensation of numbni'- is experienced. The stimulated respiration changes to a depressed one, and convulsions from this cause frequently ensue in poisoning. Vasomotor con- striction disappears, as does secretion due to pe- ripheral stimulation. The pupil often becomes dilated. The promptness with which these secondary symptoms appear is proportional to the size and con- centration of the dose, so that the primary symptoms may be almost altogether wanting. In all cases, they supervene so soon, and are so much more pronounced and continuous, that they, rather than the primary, constitute the medicinal effects of the drug. Of all, the cardiac depression and lowered arterial pressure, which are continuous, are the most prominent effects. In poisoning, conspicuous modifications of the medicinal effects occur. The tingling in the ex- tremities may become extreme. Constriction of the throat, with a sensation of strangling is also severe and alarming. Salivation and vomiting are prompt, the latter being violent, convulsive in character, and persistent. The heart becomes very erratic, although upon the whole weakness is rapidly progressive. The respiration is painfully depressed and convulsive. Muscular weakness, which may be quite persistent even after recovery, is added to nerve depression. After a very brief period of cardiac stimulation the pulse becomes slower, more feeble, irregular, and dicrotic, then flickering, ami finally imperceptible; respiration is shallow and hurried; there are chills and subnormal temperature. There is great weakness and prostration; slight exertion provokes sym and sometimes cardiac pain. The patient is in fear of death, restless: the face is pale, the lips arc blue, and the surface is covered with cold perspiration. The extremities are cold, sometimes paralyzed, and sometimes affected with pains in the joints. The eyes arc staring, glistening, and the pupils usually dilated, with more or less complete loss of sight or diplopia. In some instances the patient becomes delirious, though generally perfectly conscious to the last; sometimes he is attacked with cramps and con- vulsions, and sometimes he is comatose. The urine is generally retained. Respiratory failure is the usual cause of death. This, with cardiac paralysis, is sometimes almost instantaneous when large quant i of a liquid preparation are swallowed. Otherwise, the above-described symptoms come on successively. The tingling and numbness of the mouth are very characteristic, and are succeeded by similar sensations over the surface of the body, especially in the hands and feet. The skin soon becomes cold, though there is more or less perspiration. There is dilatation of the pupils. There is progressive muscular weakness, accompanied by feebleness and ultimately, in fatal cases, paralysis of respiration. Although some aconitine is excreted, especially by the urine, it is for the most part quickly burned up in the system, so that if a fatal result is not prompt, recovery is apt to occur. Vomiting should be en- couraged, warm water containing iodine in potassium iodide solution being used to wash out the stomach. Atropine is a physiological antidote, as is digitalis. External heat is very important. Alcohol should be used cautiously. Artificial respiration may save the patient even when death seems to be impending. Aconite is one of the most useful drugs of the Phar- macopoeia. It works especially well with children, and even very small doses often work satisfactorily. Because of the rapidity with which it is destroyed in the system, doses should be small and often repeated. The "special cases in which it is useful are those of sthenic character, in the relief of congestions. It is a very safe and moderate agent for lowering the tempera- ture, as well as for relieving tension. It tends to lessen inflammation and is especially useful in many forms of sore throat. All forms of throbbing pain, such as earache, toothache, and headache, are likely to be relieved, as are painful disorders of the respira- tory organs, such as pleurisy. Great relief is often experienced from its use in inflammatory rheumatism. Scarlet fever and the fever of measles and similar diseases are often markedly benefited by aconite, but care should be taken to avoid excessive depression. Neuralgic pains are often benefited by local applica- tions, preferably by inunction. It must never be overlooked, however, that fatal absorption may thus take place. The official preparations and their doses are as fol- lows: Fluid extract, one to two minims; tincture (of ten-per-eent. strength), five to fifteen minims. The extract, no longer official, is still considerably used, in doses of one-half to one grain. (See also Aconitine.) Other species of aconitum having similar properties in marked degree are A.ferox Wall, of India, contain- ing pseudaconitine, and A. Jiachcri of Japan, con- taining apparently aconitine, but which has been called japaconitine. H. H. Rushy. Aconitic Acid, C,H e 6l occurs in large amount in combination with calcium in aconite, also in adonis and other plants of the Ranunciilacecv and elsewhere. Either water or alcohol will dissolve it. It deposits in thin plates. This acid is also yielded upon heating citric acid. It has no special medicinal properties. II H. R. 03 Aconitina REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aconitina. — Aconitine. " An alkaloid obtained from aconite (C 34 H„NO u =640.55). As the Pharma- copoeia defines aconite as proceeding from A. napellus L., the above definition is equivalent to a require- ment that the alkaloid be obtained from that species. The percentage is variable, and should be stated in connection with every lot and preparation of the drug. Aconitine occurs in white, flat or pris- matic crystals and is soluble in twenty-two parts of alcohol, and in 3200 parts of water. When heated rapidly, it melts at 195° C. (3S3° F.), but when heated slowly, it decomposes and melts at 182° C. (359.6° F.). It is a compound of acetic acid with the alkaloid benzoyl-aconine, the latter being a compound of benzoic acid with the alkaloid aconine. Both of the two last-named occur to a greater or less extent in aconite, as derivatives of the first. Neither possesses the properties of aconitine, nor are they poisonous. To the incompatibilities of alkaloids in general, aconitine adds that of being decomposed by alka- lies, owing to its peculiar composition, as above described. The properties and uses of the alkaloid are fully stated under the title Aconite. Its activity is, how- ever, so intense that it has to be used and handled with the most extreme caution, as will be appreciated when it is considered that there is but a half pound of it in a ton of aconite, yet the safe dose of the root is limited to about five grains. Its external use is for the relief of rheumatic and neuralgic pain. The ordinary commercial alkaloid has been used in ointment up to two-per-cent. strength, but that of the pure crystalline alkaloid should be limited to 0.2 of one per cent. There is great danger of absorption, and it should be applied only to the unbroken skin. Internally, it may be used in pill form or in freshly made solution, in doses of gram 0.0001 to 0.0003 (^ to ^ grain), and not more than ten times these amounts per day. Pseudaconitine, from Nepaul or Indian aconite (.4. ferox Wall.), is equally poisonous. Its properties are under investigation, and it is not unlikely that it may be found worthy of introduction. H. H. Rusbt. Acormus. — See Teratology. Acoustic nerve. — See Ear, Anatomy and Physiology of the. Acrochordon. — From &Kpov, extremity, and yopS-fi, cord. A small fibrous growth, usually peduncular, of the skin, especially of the neck or eyelids. It may occur at any period of life but is more common in the aged. See Fibroma of the Skin, under Fibroma. Acrodermatitis Chronica Atrophicans. — This term was applied by Herxheimer and Hartmann to a type of affection previously included under idiopathic atrophy of the skin. It is also held to be a form of dermatitis atrophicans diffusa, limited to the extrem- ities; somewhat as sclerodactyl is a local type of scleroderma. Some dermatologists have insisted that these forms of atrophy of the skin must be minimal forms of scleroderma, a possibility barely mentioned by others, who merely state that the two processes show at times some points of resemblance. The initial stage shows a soft, doughy infiltration having a bluish-red hue, which is a prelude to the atrophic stage, in which the skin becomes smooth, shiny and tense. These lesions do not as a rule appear in the fingers as the name suggests, but are prone to arise in the course of the limbs, especially on the knees and elbows. Authors mention especially the "ulnar strip," a narrow atrophic band which Occupies the ulnar side of the arm. Other favorite Idealities are the face and soles of the feet. Some cases terminate in spontaneous recovery in a few weeks, while in others the affection may last for many years, yet leave no permanent atrophy. About sixty cases are on record (see also Atrophia cutis idiopathica). Edward Preble. Acrodynia. — Epidemic erythema, a somewhat obscure disease, said to bear considerable analogy to pellagra. It was first observed at Paris in 1828, occurring there as an outbreak in one of the infirma- ries for old men. The epidemic subsided during the winter months to break out again in the spring, but was considered to have been extinguished during the severe winter of 1S29-30. A few cases, however, were noted from time to time during the years 1830 and 1831, since when the affection has not again been observed in Paris. In Mexico, in 1866, during March and April, an epidemic said to be acrodynia broke out among the Mexican and Algerian soldiers at Zitocuaro. On the Continent it had been observed on a small scale since 1831, chiefly among Belgian and French soldiers and prisoners, the last occasion being in a French regiment stationed at Satory, near Versailles, in 1874. This epidemic was not very clearly demon- strated, however, to have been one of acrodynia, and of late the existence of such a disease has even been questioned. The general symptoms are said to be in some respects similar to those of chronic arsenical poisoning. Commencing with gastrointestinal irri- tation, redness of the conjunctiva, edema of the face or limbs, there are soon added formication, pains in the fingers and toes, a burning sensation, and pricking or shooting pains in the palms and soles, and a feeling of weight in the extremities, especially the lower. Hyperesthesia of these parts, especially the soles of the feet, and sometimes anesthesia, are present. Cramps, spasms, and tetanic contractures are almost always constant symptoms. There is no fever, and the disease is rarely fatal, except in the old and feeble or from the diarrhea which is present in all cases, recovery taking place in a few weeks or months. The chief cutaneous manifestations of the disease are erythematous and pigmentary. The erythema makes its appearance early in the course of the disease and may be very general, affecting, however, chiefly the extremities, more particularly the hands and feet, and here especially their palmar and plantar surfaces. It may be pre- ceded or accompanied by the formation, chiefly on the hands and feet, of vesicles or bullae filled with a clear or at times more or less sanguinolent effusion, and is followed by desquamation or exfoliation of the epidermis, while a dark brown or blackish pigmenta- tion spreads itself over the abdomen, chest, axilla?, and other parts, being more pronounced in the warm regions of the body. Alibert, in his description, the only one coming from a dermatologist, says (" Mono- graphic des dermatoses," Paris, 1S33, p. 12) that what particularly attracted his attention in most of those afflicted with the disease was this black color which affected the integument, nearly all who presented themselves for treatment having the tint of a chimney sweep. The pathology of the disease is obscure; there are no special postmortem changes, but in several cases in- flammation of the pia mater and spinal arachnoid was found. Though the disease bears a close resemblance to pellagra, the general and cutaneous symptoms are more varied in acrodynia than in pellagra; and while in the latter the backs of the hands and feet are attacked, it is the palms and soles that are affected in the former. The disease was regarded (Chomel, Recamier, etc.) in Paris as being due to spoiled cereals, but nothing positive on the score has been proven. The most efficient treatment was claimed to consist in counterirritation of the spine. Charles Townshend Dade. 94 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acronwualy Acromegaly. — Synonyms: Megalacria, acromegalia, pachyacria, Mane's disease. Definition. — Acromegaly, from inpov, extremity, and uiyat (fiej-aX-), great, is a chronic disease, charac- terized by an abnormal increase in the size of the extremities, viz., hands, feet, and generally head, due to an hypertrophy of the bones and soft parts of these regions. History. — The first to recognize this disease as a Separate entity was P. Marie, who wrote upon the subject in the Revue de Medecine, vi., 297, 1886, describing two cases which he had discovered while assistant to Professor Charcot. The first cases dis- covered and reported as acromegaly (in 1885 Wads- worth reported a case as myxedema which was un- doubtedly acromegaly) in America were those of O'Connor and Adler, both of which were published in 1888. For the early bibliography the following may be consulted: New Sydenham Society Reports, London, 1891; Joseph Collins' articles in the Journal of Nervous and Mental Diseases, December, 1892, and January, 1S93, the alphabetical bibliography in the writer's article in the Yale Medical Journal, Decem- ber, 1S97; Guy Hinsdale's monograph in Medicine, 1898; and the chronological bibliography of Harlow Brooks in the Archives of Neurology and Psycho- Pathology, vol. i., No. 4, 1S9S. The later bibli- ography is given in the monograph of Bernhard Fischer, "Hypophysis, Akromegalie und Fettsucht," Wiesbaden, 1910. Symptomatology. — General Condition. — The acro- megalic patient comes to the physician complaining of headache, disturbances of vision, severe joint pains, and sometimes ringing in the ears; or the condition is discovered while the patient is under treatment for an entirely different disease. The pain in the head is the most frequent subjective symptom, and is often severe and even terrific. There may be, and fre- quently are, pains referred to various parts of the body, often to the joints, which are more or less per- sistent but neuralgic in character. Frequently there is tingling of the hands, feet, or ears, often with numbness of the fingers, but with no great loss of sensibility. There are generally increased and often ravenous appetite, increased thirst, dyspepsia and polyuria, and generally constipation. As a rule, in women menstruation is absent and in men the sexual appetite is diminished. The weight during the developing period of the disease always increases, and so does the height to a certain extent, at least till the period when kyphosis develops, when more or less loss of height takes place The gradual increase in the size of the hats, shirts, gloves, and shoes worn affords evidence of the enlargement of the head and extremities. In women the increase in the size of the fingers, as shown by the inability to wear the wedding ring, is a positive evi- dence of growth. In most cases earlier photographs of the patient can be obtained and compared with the present condition. Clinical Inspection. — In acromegaly all of the pro- jecting portions of the body are greatly enlarged — hands, feet, chin, lips, nose, tongue, ears, and often the genitalia. Of these parts the bones, cartilages, and soft tissues are all hypertrophied. The face is oval, the cheeks are flattened, the forehead is retreat- ing and low, the nose enlarged and often massive, and exophthalmos may be present. The ears are gener- ally enlarged and the hair of the head is strong and thick. The intellectual faculties may or may not be impaired, and somnolency is sometimes present. Taste and smell are rarely affected, while hearing is occasionally disturbed and sight is frequently im- paired. The voice is loud and deep. The reflexes are generally normal, at least not markedly impaired, and the electrical reactions are normal. lhiul. — The forehead is low and retreating, due to the growth forward of the superciliary ridges, which, with the elongation and forward projection of the lower jaw, gives the oval or elliptical face so charac- teristic of this disease. The hair is thick and strong, and the eyebrows are often heavy. The face is entirely too large, being out of all proportion to the cranium proper. The skin of the face is thickened and of a yellowish-brown color, most marked on the eyelids, with perhaps here and there a molluscous growth. The skin of the forehead is often redundant and thrown into many transverse wrinkles and folds. The cheeks are flattened, and appear sunken, largely due to the prominence and projection of the malar bones. The circumferences of the orbits are promi- nent, and the eyelids are large, due to the thickening and widening of the tarsal cartilages, with more or less hypertrophy of the skin, especially of the lower lid, where it may fall in folds, with occasionally the appearance of edema. The eyeballs are large and generally more or less prominent, even to the con- dition of exophthalmos. The nose, even for the size of the face, is too large, often immense, due to the thickening of the nasal cartilages and to the great hypertrophy of the soft parts. It is wide, thick, and may be pugged. The mucous membrane is often thickened. The superior maxillary bones may or may not be enlarged, but are frequently lengthened from above downward; however, they are never enlarged to the same extent as is the lower jaw. The upper lip is generally thick and projecting, but never attains the size of the lower lip. The lower lip is almost in- variably thick, everted, and projecting, and is a characteristic feature. The enlargement of the lower jaw is one of the characteristic changes in this disease, although acro- megaly can occur without it. Sooner or later prog- nathism generally occurs; it is due not only to the growth of the body of the lower jaw, but also to the widening of the angle and the changes in the glenoid fossa. The external ear is generally increased in size. The cartilages and the soft parts both take part in the growth, and the former may become in places as hard as bone, while the external auditory canal may be lengthened by the growth of its cartilage and nar- rowed by exostoses from the bony wall. The tongue is broad and thick and frequently double its normal size, almost entirely filling the cavity of the mouth, so that the sides show indenta- tions from the teeth. The upper surface of the tongue is often deeply corrugated and marked by deep lines and fissures, and the papilla? may be prominent and projecting. The speech is rendered thick, heavy, and slow by the massive tongue, while the prog- nathism allows the labial and dental sounds to be but poorly articulated. The tongue is generally clean, but may be covered with a grayish-yellow coating. The soft palate is often thickened, the uvula may be wide and long, even as large as a little finger, and the epiglottis has been found considerably thickened. The larynx is enlarged, either as a whole or in one or more sets of its cartilages. The aryepiglottic liga- ments may be thickened and the vocal cords hyper- trophied. These laryngeal enlargements cause the voice to be loud and" harsh, while the pitch is much lowered in men and made masculine in women. The submaxillary and the lymphatic glands of the neck may be enlarged. The thyroid gland nvay be normal in size, hypertrophied, cystic, or so atrophied that it cannot be found. The neck is short and thick, and the head leans forward, while the cervicodorsal kyphosis causes the long projecting chin almost to rest on the sternum. Body. — Sooner or later the irregular growth of bone in the spinal column causes deformity of the spine. This deformity is almost constantly a cervicodorsal 95 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES kyphosis, giving a humpback appearance which is very characteristic of this disease. Occasionally scoliosis is also present, and sometimes there is a compensatory lumbar or dorsolumbar lordosis. The spinous processes of the vertebrae may be abnor- mally prominent, especially the lower cervical. The size of the chest is greatly increased, especially at the level of the ensiform cartilage, where it reaches its o-reatest circumference. Laterally the chest Flu. 24. — Acromegaly. (Author's Case.) appears flattened, while the anteroposterior diameter is often enormous, due to the forward projection of the lower end of the sternum. The sternum is generally widened and thickened, with prominent transverse ridges. The xiphoid cartilage is hard, wide, ami projecting. The clavicles are most enlarged at the sternal extremity, but the acromial end is also thick- ened. The ribs are wide and very oblique, and al their junction with the more or less enlarged and ossified costal cartilages are found bony nodules, not unlike the rachitic rosary, and nodosities may appear on the ribs themselves. The hardening of the liga- ments iiiid cartilages of the chest causes a peculiar stiff and constrained up-and-down or out-and-in 96 motion of the lower part of the thorax during respira- tion, and the abdominal respiration is increased. The abdomen is generally flattened and even ap- pears retracted from the forward projection of the sternum and costal cartilages, though rarely it may be large and pendant. The pelvis is enlarged, the ilia are wide apart, the crests broad and prominent, and the pubic bones are especially hypertrophied at the symphysis. The external genitals may or may not be enlarged. The clitoris may be hypertrophied, and the vagina may be lengthened, but the uterus is generally small and atrophied. Upper Extremity. — The shoulder joint may be, but rarely is, much enlarged; the elbow joint may be in- creased in size; the forearm is often enlarged at its lower third, especially just above and at the wrist; the wrist joint is almost always large. The hand, widened, thickened, and often lengthened, is massive and enormous, and appears heavy and cumbersome for the relatively small arm to carry. The ends of Fig. 25. — Typical Hand in Acromegaly. (Author's Case. ) the metacarpal bones and phalanges are enlarged, giving prominent joints. The skin of the hand and the subcutaneous tissues are greatly hypertrophied, so that the normal lines of the palm are greatly deepened. At the upper part of the hand, and over the metacarpal bone of the thumb, and on the ulnar border, the hypertrophy of the soft parts is excessive. The fingers, by the growth of phalanges and soft parts, become of the same width and thickness at the tips as at the bases, giving the appearance called "sau- sage-shape," which is a characteristic feature of this disease. The fingers may appear somewhat flattened, unci, according to Marie, there is often a swelling at the articulation of the first and second phalanges. The nails are flattened, short, and sometimes widened, but always appear too small for the enlarged fingers, whose redundant flesh laps over them at the sides. There are strongly marked longitudinal striatums, sometimes even with ridges, and there may be trans- verse striations on the nails. They are often brittle, breaking off or cracking easily. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES PLATE V Fig. 1. Fig. 2. Fig. 4. Acromegalic Skeleton (Osborne's Case) At the Yale Medical School Fig. 1. — Normal skeleton. Fig. 2. — Skeleton of Acromegaly showing Kyphosis, enormous anteroposterior diameter of thorax, great obliquity of the ribs, long arms reaching almost to the knees, large feet, great project- ing os calcis, etc. (author's case). Fig. 3. — Spine of Fig. 2; shows co-ossification of bodies oi dorsal vertebrae and many bony unions of spinous and transverse processes. Fig. 4. — Skull of Fig. 2, showing enormous inferior maxilla, prognathism, projecting supraorbital ridges, large and prominent malar bones, etc. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acromegaly Lower Extremity. — The thighs are generally not in- creased in size, although the condyles of the femurs may be prominent and enlarged, which with the hy- pertrophy of the patellar causes a marked enlarge- ment of tin' knees. The upper ends of the tibiae and fibulae may or may not be enlarged, but the lower ends of the leg bones are generally found hypertrophied, causing prominent malleoli and large ankle joints. The tendo Achillis is frequently prominent and hard- ened. The bones of the feet are all enlarged, especially the os calcis, which projects backward, giving a marked prominence to the heel. The foot is thick and broad, with a prominent cushion of thickened skin and subcutaneous tissue on the external border, a characteristic feature of the foot in acromegaly. The toes are all large, but more especially the big toe, which is immense, and crowds the other toes together. The skin of the foot is redundant, hypertrophied, and thickened, especially on the toes. The nails of the toes present appearances similar to those of the fingers. Acromegaly is primarily a symmetrical disease, one part enlarging correspondingly with its fellow on the other side; but exceptionally one side of the body, more often the right, is larger than the other. Be- sides this slight asymmetry of the two sides of the body, some atypical cases have occurred in which one or several toes or fingers were found to be larger than their fellows, or one side of the face and head was much larger than the other side. Muscles. — At first the muscle growth and muscular power are increased, and sometimes the development of the muscles may be very great. Sooner or later, however, the muscles become atrophied in greater or less degree, and the muscular power is greatly dimin- ished, even to the point of compelling the patient to remain in a sitting or reclining posture, or in bed. There may be intermittent attacks of great loss of muscular power, followed by periods of improved strength. Skin. — The subcutaneous fat may be increased or diminished, but later it is generally found diminished, except perhaps on the diseased portions of the body. The skin on the affected parts is hypertrophied, and where exposed is olive brown or yellowish in color. This yellow color is most marked on the face, and here most noticeably on the eyelids. The face may, however, be pale, or the nose may be red, and the skin may be dry and harsh from diminished sebaceous secretion. There is frequently increased perspiration, coming on with slight exercise, or even without ex- ercise, either general or local on the diseased portion of the body, and especially frequent on the legs. This perspiration may have a disagreeable odor. The growth of the hair all over the body is increased, especially on the legs, and on the head it is thick, strong, and coarse. There may be pigmentations on the skin, and pendulous growths of molluscum fibro- sum frequently occur on the face, especially on the eyelids, and on the chest or back. Multiple fibro- mata of the skin may occur, of the size of a millet- seed, and fatty nodules may be found beneath the skin. Blood-Vessels . — There are always vasomotor dis- turbances of the affected portions of the body, as shown by the tingling, flushing, and local sweating. The flushing is often accompanied by a "burning pain." Besides these signs, which denote the dilata- tion of the small blood-vessels, there is a marked tendency to a dilated and varicose condition of the Superficial veins, especially of the legs. Hemorrhoids are often present, varicocele may be, and profuse epistaxis may occur, while the arteries may show signs of beginning atheroma. Albuminuria or peptonuria may be present, while polyuria is a frequent symptom. Glycosuria has been so many times present as to suggest some metabolic connection between pituitary disease and disturbances of the sugar mechanism. Vol. I.— 7 Sight. — .More than half of all cases of acromegaly show deranged vision or optic signs during some stage of the disease. The physical cause of the ocular disorder is largely the pressure of the enlarged hypophysis on the optic chiasm. That in some cases one eye, in others both, and in still others the ears alone are affected can be explained by the con- dition of the bony environments of the sella turcica in the individual skull, the enlarging pituitary body tending to escape in the direction of least resistance. If the middle clinoid processes are small, the pressure will be exerted early on the optic commissure; or if one of these processes is smaller than the other, the pressure will first be exerted on that side, and but one eye may be affected. Exophthalmos is often present, due both to actual enlargement of the eyeballs and to bony growth in the orbital cavities, or perhaps to associated thyroid disease. The pupils are generally normal in size, but may be dilated, and the reaction may be slow to light but normal to accommodation. Nystagmus, both rotary and vertical, has been present, and divergent strabismus has been noted in a few cases. Narrowing of the visual fields has been found in all degrees, even to bitemporal hemianopsia, and signs of optic neuritis due to pressure may be found even before the vision is much impaired. Optic atrophy, partial or complete, of one or both eyes, is of frequent occurrence. The retina? may show venous congestion, and the arteries may be small or they may appear pale, or a congestion as of a neuroretinitis may be present. Hearing. — The hearing is not generally affected, but occasionally there has been decided deafness, and in several cases there has been continuous and unceasing tinnitus aurium. When this is constantly present there is either pressure on the cavernous sinuses by the enlarged pituitary or an actual growth into them of the pituitary tumor. The ringing is often in- creased on lying down, so that the patient cannot sleep except in the sitting position, and anything that increases the blood pressure even momentarily will increase the tinnitus and often give it a pulsating character. The drum membrane may be hardened, thickened, and almost immovable. Smell and Taste. — These are but rarely affected. Nervous Phenomena. — A most constant symptom is pain in the head, which may be referred to any region, but is generally frontal or vertical; in one of the writer's cases it was located in a small circumscribed spot, tender to pressure, over the region of the anterior fontanelle. This pain may be so mild that it is hardly complained of, or so violent as almost to render the patient insane. The headache is often, like the tinnitus aurium, made worse on lying down or by anything that increases the cerebral blood pressure. Pain may be present in the joints, especially the knees, and is often severe in the fingers. Pain is frequently complained of in the chest or abdomen, shooting around the body or confined to one side, or it may be lumbar or sacral. Almost every subject of acrome- galy has pain, more or less constant and severe, in some part of the body, often without any local cause. Crepitations may be found in some of the joints, which, of course, would account for the pain there, though there is no swelling or any evidence of acute inflammation. Sometimes a peculiar nervous sensation is com- plained of, a sensation as of a nervous discharge or electric shower, starting from the top of the head and passing quickly over the body to the feet. This is sometimes described as giving the sensation of the rolling of shot; hence it has been termed the "shot feel." There are no marked or constant paresthesias in acromegaly, though slight numbness or prickling of the affected parts is often complained of, most fre- quently in the fingers. The tactile sense of the fingers may be impaired, so that small objects can- 97 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES not be readily handled, and sewing, knitting, or even dressing becomes difficult. Sometimes an inter- mittent vasomotor spasm in the fingers has been noted, causing localized anemia with severe pain, while formication or hyperesthesia of the hyper- trophied parts may occur. General numbness anes- thesia, analgesia, and impaired perception of heat or cold, are rare conditions in this disease. The electrical responses of the muscles and nerves are rarely abnormal, and the reflexes, both deep and superficial, are generally unimpaired. Occasionally the patellar reflex is diminished, and rarely it is absent on one or both sides. The mental faculties in the majority of cases are not affected, but loss of memory, dulness or sluggishness of the mind, apathy, and depression have all been recorded. Marie says that there may be a state of gnat good humor, but, on the contrary, melancholia is more frequent. There may be great irritability, while there may be delusions, and the patient may be refractory and suspicious; he may develop de- cided insanity, and may even show suicidal and homicidal tendencies. This condition may be persis- tent or intermittent, or may last for a short time and not recur. Another interesting condition which seems quite frequently to occur in acromegaly is a persistent drowsiness even to somnolency. Vertigo may occasionally occur and be severe enough to cause the patient to grasp something for support. At- tacks of syncope are sometimes a frequent symptom. It is probable that the conditions showing sudden and serious brain trouble, all of which point to cere- bral tumor, are due to the first sharp pressure which the enlarged pituitary body exerts upon the brain, having perhaps suddenly burst from its bony moorings. Pathological Anatomy. — Hypophysis Cerebri. — A lesion of the anterior lobe of this structure is probably always present in cases of acromegaly.. Fia. 26. — Section of Parenchyma of the Thyroid filand. The whole gland weighed 101 grams. (Author's Case.) Usually there is a distinct enlargement, or hyperplasia (adenoma), of the anterior lobe, but it may be normal in size or there may be cystic or other form of de- generation, the latter being probably always second- ary. The changes found here will be discussed in the section on Pathogenesis. 98 Thyroid. — The thyroid gland is not infrequently ab- normal in acromegaly. It may In- hypertrophied and give a hypersecretion and all of the symptoms of exophthalmic goiter, or it may be atrophied and cause some myxedematous symptoms, or, which is probably most frequently the case, the gland is first hypertrophied and then connective-tissue growth displaces the glandular parenchyma, and though the gland is actually enlarged, it is producing a diminished secretion, and a partial myxedema occurs. This accords with the symptoms of a long-continued acro- megalic case, and with the frequent autopsical " ' -V* - ' • ■ . ■ • . 9 *f iu> N % 1 ■ ft ) Fig. 27. — Section of Thoracic Thyroid Gland. The whole gland weighed 36.5 grams and contained a large amount of iodine. (Au- thor's Case.) finding of an enlarged and heavy thyroid gland sometimes containing a greatly diminished amount of iodine. This gland may also show cystic degenera- tion. In one of my cases a large supernumerary thyroid gland was found in the upper part of the thoracic cavity, which contained a large amount of iodine. Thymus. — The thymus gland has several times been found enlarged and in one instance a fatty growth in the region of the thymus has been reported. In these cases instead of thymus glands they may have been supernumerary thyroids. A thymus gland contains no iodine (Mendel). Brain. — The brain has frequently been found en- larged, but may not be, even in cases which show increase in size of almost every other organ of the body. The pineal gland has been found double its ordinary size, and little tumor growths have been found attached to the base of the brain. Calcified and even ossified plates have been found in the dura mater, and its attachments to the skull may be ossified. The arteries at the base of the brain may be enlarged and thickened, especially some one artery in the circle of Willis, while another artery or another part of the same artery may be distinctly narrowed. The arteries may become distorted and tortuous, and the posterior cerebral has been found knotted and imperforate. The cranial nerves have been found either normal or enlarged. The nerve changes in the brain and cord, if there are any, are probably secondary to the Vascular changes. As in this disease we find the blood-vessels almost con- stantly changed, we may expect to find all kinds of changes due to a greatly modified blood supply, be it in an organ or in nervous tissue. Spinal Cord and Nerves. — The medulla and spinal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acromegaly cord are generally normal, but the pia of the cord has b een found I hickened, and some of the columns of the ,.,,i,l may be degenerated. Probably, however, as above stated, all nerve degenerations of the brain or spinal cord are due to foregoing vascular changes. The nerves of the body, and especially of the extremities, may be enlarged generally, this change being due to an increase in the interstitial connects e tisane. They may show sclerosis in some places and fat tv changes in others, and their vessels may show hyaline degeneration. flu i -*'' < Fig. 2S. — Section of the Pituitary Body. (Author's Case.) The ganglia and nerves of the sympathetic system show no special changes, though they may beenlarged, and from the same cause as in the case of the spinal nerves, viz., from connective-tissue growth. Heart. — The heart is probably always enlarged in acromegaly, by reason of an actual hypertrophy, especially of the left ventricle; this being due to the increased work which it must perform in overcoming the resistance offered by the thickened blood-vessels. Later the heart, though hypertrophied, becomes weakened by the impaired action of its muscle fibers due to connective-tissue formation or perhaps to the presence of fat globules, or else to the impaired blood supply of its walls, which in turn is due to thickening of the intima of its own nutrient blood-vessels. Blood-Vessels. — The vascular changes are a con- stant feature of acromegaly, the intensity of these changes or their localization causing the many variations of symptoms or conditions seen in different cases of acromegaly. More or less generally all over the body the coats of the arterioles are thickened, the intima being the most affected. This may also be true of the veins, although in many places the vein walls seem to be thinned, allowing varicose conditions to take place. This may occur in the lower extremi- ties, or as hemorrhoids, or in the large veins of the arms and neck. The epistaxis noticed in some cases is probably due to this weakening of the blood-vessels. The blood is normal, or late in the disease it may show simple anemia. Lungs. — The lungs are not often affected, but many times, both in autopsical reports and in clinical accounts of cases of acromegaly, "phthisis" has been mentioned, or tuberculous consolidation has been found. Chronic bronchitis, edema, or passive con- gestion can develop from a weak heart action in the later stages. The Digestive System. — The stomach and intestines present no specific abnormalities. The pancreas often shows changes, especially in those cases in which glycosuria has been present. The liver is generally enlarged, sometimes very greatly, and mav show a great increase in connective-tissue growth (hypertrophic cirrhosis). There may be a passive congestion or fatty degeneration of the liver. The spleen may be enlarged by passive congestion and an increase in its connective tissue. Genito-Urinary System. — The kidneys are often found diseased (chronic nephritis), or I hey may be cystic. They and the suprarenal glands may be increased in size. Microscopical examination of the genitals shows an increase in connective-tissue growth and even al limes the formation of fibrous tissue; these I'li.r being accompanied by a gradual diminution of all functional activity. Skin. — The skin is hypertrophied over the affected portions of the body, sometimes in a marked degree. This is especially true of the scalp, hands, and feet, all of the layers of the skin taking part in this thicken- ing. The sweat glands may have a double layer of epithelium. Fibromata, neuromata, and elephantia- sis of the skin have been observed, and molluscous growths are of frequent occurrence. The sub- cutaneous fat may be increased or decreased in thickness, but in the later stages it is probably nearly always decreased. Muscles. — Many of the muscles at the time of death, unless I he patient dies early in the disease from some intercurrent affection, are found atrophied, and yet there may be many local hypertrophies. Certain muscles, especially the deltoid or the supraspinatus, may become greatly hypertrophied, forming veritable muscle tumors. Fir,. 29. — Section of Branches of Vessels near the Posterior Tibial Artery, Showing Thickened Intima. (Author's Case.) Skeleton. — In well-marked cases nearly all of the bones of the body are enlarged, although a few individual bones may not take part in this increased growth. The long bones undoubtedly show the greatest enlargement and growth at their extremities, due to the tendency of the articular cartilages to ossify; still in many instances the shafts of the bones are also decidedly enlarged. The spongy bones of the skeleton are all more or less thickened, and all articular surfaces, whether of long or spongy bones, show a tendency to spread out, widen, and grow more prominent. The flat, thin bones, while increasing in extent show a tendency to become thinner in their plates. This is not true of the cranial bones, because the spongy tissue in the diploe increases in thickness. We sometimes find a thinning at the ends of the long bones, just back of the articular surfaces, while they are at the same time extending their articular sur- faces. This growth of bone is an hypertrophy, the 99 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES new bone growing from the periosteum and also "within the medullary spongy tissue at the ends of the long bones. In the early part of the disease this growth seems to be more especially confined to the periosteum; later the apophyses and epiphyses become affected. The crests, tuberosities, and eminences are enlarged and grow in the direction of the muscular action, a portion of the tendons of the muscles becoming ossified. The tendons of the muscles are often found in deep grooves or bony canals, and the foramina for the nutrient arteries, and especially for the articular arteries, are often enlarged. Osteophytes may be found in the joints, especially over the wrist and ankle joints, or pieces of calcareous material may be found loose in a joint. The spongy ends of the long bones may become more compact, through eburnation and a change in the architecture of the part. The ends of the bones in some cases have shown condensing osteitis. This laying on of bone at the extremities, the articular surfaces, may lengthen a long bone without the shaft being at all affected. Head. — The bones of the cranium are always more or less thickened, this change being due largely to an increase of the diploe. The ridges and crests for the attachment of the muscles and fascia? are more promi- nent, while the occipital protuberance has been found as a spicula-like outgrowth, an exostosis. The parietal eminences are sometimes abnormally promi- nent, as are always the superciliary ridges. The sella turcica is always enlarged and deepened, probably because the enlargement of the pituitary body causes the surrounding bone to undergo absorption. The lengthening of the face is largely due to the increase in the vertical diameters of the superior and inferior maxilla?. The maxillary bones and the sphenoid bones contribute the principal part of the total enlargement of the bones of the skull. Many of the sutures of the cranium and of the face are obliterated by complete co-ossification. The enlarging malar processes, orbital processes, and nasal processes of the superior maxillary bones cause the pushing outward of the malar bones, the lateral widen- ing of the orbital cavities, and the pushing upward of the nasal bones, thus causing the prominence of the malar bones, the quadrilateral appearance of the orbital cavities, and the wide nasal openings seen in skulls of acromegaly. The lower jaw is massive, the chief growth being in the body, which is found lengthened and widened, especially at the symphysis, while the mental process stands out with undue prominence. The alveolar process is widened and thickened, and the rami also may take part in the growth, while the angle formed by the junction of the body and the rami becomes more obtuse. The coronoid processes are often greatly enlarged. The growth of the alveolar process is rarely participated in by the teeth, they remaining normal in size, so that while the alveolar cavities undergo enlargement we frequently have spontaneous falling out of the teeth. The hyoid bone may be enlarged with all of its ridges very prominent, and the laryngeal cartilages may al>u I nlarged. Spine. — Marked changes are always found in the spine, the degree being due to the age of the disease. The bodies of the vertebra? are enlarged, especially from the laying on of bone on the anterior part in the cervical and dorsal regions. The increase of bone in this region is often restricted to the upper part of the interarticular cartilages, while in the lumbar region the increase of the bone is more general. The irregular thickening of the intervertebral carti- lages, with the irregular growth of the bodies of the vertebra?, sooner or later causes deformities of the spine, namely, kyphosis, lordosis, or scoliosis, or more than one deformity. An absorption of the inter- vertebral discs, especially on the anterior borders. with bony union of the anterior parts of the bodies, and ossification of the anterior ligaments, which often occurs, may cause an enormous kyphosis, the anterior part of the spine appearing, under these circumstances, as if formed of a single bone. The transverse processes probably always are enlarged, and may be joined together by the ossifica- tion of their connecting ligaments. This ossification may take place along the interspinous ligaments, or we may find ossification of the posterior intervertebral ligaments. The lumbar vertebra? are sometimes of great size, and the sacrum may have its lateral masses much enlarged. Thorax. — The sternum is enlarged and thickened, and the ensiform cartilage is ossified and generally projects outward. Large transverse ridges are often found on the sternum; also a hollow or depression may be seen at the upper part, due to the manu- brium not enlarging relatively as much as the body of the sternum. The costal cartilages are large and more or less ossified, and often show prominent nodes at their points of junction with the ribs, thus simulating the rachitic rosary. The ribs are wide and thick, and by the faster growth of the costal cartilages they become abnormally oblique, while the sternum itself is pushed forward, giving an enormous anteroposterior diameter to the chest. Upper Extremity. — The clavicles are always en- larged, often enormously so, most marked at their extremities, and especially at their sternal ends. Their ridges and tubercles are very prominent. The scapula? are generally enlarged, especially in their transverse diameters, and the spines may be enor- mous in size. Fir,. 30. — .Skiagram of the Right Forearm and \\ rist. (Author's Case i The articular surfaces of all the long bones are en- larged, due to ossification of the articular cartilages or ligaments, and they are often roughened. There may be exostoses, spongy growths, osteophytes, or calcareous deposits in and around the joints. The humerus is frequently not increased in size, though its extremities, especially the head, may be. The radius and ulna, if the case is of long standing, are found enlarged, especially at their articular sur- faces, and more especially at their lower extremities. 100 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acromegaly The carpal bones are always more of less enlarged, md may all be very markedly so. The metacarpal bones and phalanges are widened and thickened; the former especially at their heads, and the latter at each jxtremity, thus rendering the joints prominent. The listal phalanges are generally the most affected, and nay show an increase of spongy tissue at their ungual •IK is. /', (,-;*. — The pelvis is always enlarged, with the symphysis of the pubic bones often wide and deep, while the crests of the ilia are wide apart, by reason of Fig. 31. — Skiagram of Part of an Acromegalic Hand, Showing Hy- >ertrophy of the Soft Parts and Increase of Spongy Tissue at the Jngual Ends of the Distal Phalanges. (Author's Case.) i spreading out of the ilia. Though the pubic bones tnd the iliac bones may be enlarged, with their ridges md eminences increased in size, and with the obtura- tor foramina enlarged, the substance of the bones hemselves may be considerably thinner than normal. rhe acetabular cavities may be enlarged and rough- ;ned by partial ossification of the cotyloid ligaments. Lower Extremity. — The femurs maybe enlarged at X)th extremities, as may also be the heads of the ibia? and fibulae. The patella are often hypertrophied uid may present abnormal spinous processes. The nalleoli are large. All of the tarsal bones may be enlarged; especially is the os calcis often enormous, m account of the laying on of bone at the attachment if the tendo Achillis. The metatarsal bones and the Dhalanges of the toes are all enlarged similarly to ;hose of the hands. Thompson found several of the phalanges of the toes ossified together. The distal phalanges may show spongy enlargements at both extremities, and there may be spongy spicules of bone which reach around from one extremity to the other, forming foramina or incomplete notches on the sides of the bones. Pathogenesis. — Some of the earlier theories of the pathogeny of this condition may be mentioned, but they are purely of historical interest, being no longer accepted as true or even probable. Marie's theory was that acromegaly is dependent upon a diminished pituitary secretion, this resulting from more or less destruction of the gland by a new growth. The new growth, however, is usually an adenoma with increased secretion, and when it is not, it is a secondary degenerative lesion occurring late in the course of the disease after the mischief has been done. Freund and also Campbell suggested that acromegaly was a disease of puberty, an atavistic anomaly of development manifesting itself at this period, the body in its entire development at this time harking back to the anthropoid apes. There is, however, only the very faintest superficial resemblance between the p-athological anatomy in acromegaly and the normal anatomy of the ape. Von Recklinghausen, Lancereaux, and others have inclined to the view that acromegaly is a trophoneu- rosis. It is true that vasomotor disturbances, neu- roses, and trophic changes are present in acromegaly, but they are dependent immediately upon the hypo- physeal overgrowth or oversecretion, and only remotely, if at all, upon central nerve lesions. Klebs believed that the underlying lesion was an angiomatosis, basing his theory on the undoubted fact that signs of vascular disturbance are present in acromegaly. The blood-vessels are increased, it is true, but only, as a rule, in proportion to the general hypertrophy of the bones and soft parts. Other writers have ascribed the presence of acro- megaly to lesions of the thyroid gland, or to a per- sistent thymus. The thymus is seldom persistent in acromegaly, however, and many cases occur with- out any evidences of thyroid lesions. Spitzer offered the suggestion that the disease was due to an error in development, viz., an inclusion and subsequent growth of spinal cord rests in the hypo- physis cerebri. This theory is of course in the highest degree fanciful and unsupported by anatomical findings. Another fanciful suggestion is that of Yu Kon that the changes in acromegaly are due to pressure upon some as yet undiscovered trophic center at the base of the brain by the pituitary tumor. Aside from the gratuitous assumption of the existence of an unknown center here, the fact that cases of acromegaly un- doubtedly occur without any enlargement of the hypophysis would seem to dispose of this theory. It has been asserted by more than one writer that acromegaly is due to an aplasia or degeneration of the sexual glands, this view being supported by a supposed resemblance of the skeleton in a castrated person to that in the disease in question, and also by the undoubted fact that there is frequently more or less loss of the sexual function in the subjects of acromegaly. In such a theory the consequence in mistaken for the cause, for there can be little question that the sexual disturbance is a secondary condition. At the present time it is quite generally accepted that acromegaly is due to some perversion of secretion of the hypophysis cerebri, but what this perversion is, whether hyperpituitarism or hypopituitarism, is even yet a subject of dispute. Because of the fre- quent association of a tumor of the anterior lobe of the hypophysis, Marie believed, as above noted, that the condition was one of lessened secretion; but opinion inclines now rather to the opposite view, 101 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES namely that there is a supersecretion of this portion of the gland. A more careful study of the so-called tumors of the anterior lobe in these cases has shown that the condition is one rather of hyperplasia than of degenerative neoformation; the secreting cells are not displaced by a cystic growth or neoplasm, but are increased by reason of an adenomatous develop- ment. In some instances, it is true, there is no tumor or hypertrophy of the anterior lobe and there may even be an apparent atrophy. In order to reconcile such findings with the theory of supersecretion three explanations have been offered. The first is that though no gross changes are evident there may nevertheless be found microscopically an increase in number of the specific secreting (eosinophile) cells, or there may possibly be a more active secretion without increase in number. Another theory is that of Tamburini that there is a primary hypertrophy of the anterior lobe, which after having produced the mischief, is succeeded by atrophy. The third hypothesis rests upon the recent discovery of acces- sory hypophyseal glands in the vault of the pharynx. Killian (1888) and Eidheim (1904) noted the presence of hypophyseal tissue in the vault of the pharynx in the newborn, and Civalleri (1907) and Haberfeld (1909) showed that an accessory pituitary gland may exist in this situation in the adult. Moreover, hypo- physeal rests have been noted by Eidheim and Levi in recesses in the sphenoid bone in connection with a persistent craniopharyngeal canal. It is possible therefore that these accessory glands, acting with a normal pituitary body, may produce an excess of secretion and so cause acromegaly. While either one or all of these hypotheses may be alleged in support of the view that acromegaly is the result of a superfunctioning of the hypophyseal cells, it must be admitted that the problem is not yet satisfactorily solved, even though the weight of evidence is in support of supersecretion rather than of subsecretion. One of the strongest arguments against this is the fact that there may be a true adenoma of the hypophysis without any signs of acromegaly. The explanation of such cases, if the theory of supersecretion is accepted, is difficult. It has been suggested that the increase in pituitary secretion may here be counteracted by a coincident increase in the internal secretion of the sexual or some other glands; but this is a supposition only, not an explanation, and is no more satisfactory than a simple denial of the fact. For a discussion of the physiology and pathology of the pituitary, body, the reader is referred to the article on Hypophysis Cerebri. Diagnosis. — This disease must be diagnosed from myxedema, gigantism, erythromelalgia, elephantiasis, leontiasis ossea, chronic rheumatism, syringomyelia, rachitis, osteitis deformans, arthritis deformans, pulmonary hypertrophic osteoarthropathy, local hypertorphies, and adiposis dolorosa. The principal- clinical differences between myxe- dema and acromegaly are as follows: Acromegaly. 1. Both sexes are about equally affected. 2. Begins most frequently be- tween the ages of twenty and forty. 3. Bones are always enlarged. 4. Face is oval or elliptical. 5. The ends of the fingers are of the same size as the bases, i.e. they are "sausage-shaped." 6. The skin is yellowish, wrinkled, and hairy. Myxedema. 1. About eighty per cent, of all cases are women. 2. Occurs most frequently be- tween the ages of forty and fifty. 3. Bones are never enlarged. 4. Face is round and full. 5. The ends of the fingers are swollen and clubbed. 6. The skin is pale, waxy, puffy, boggy, and shiny. Gigantism, or giant growth, is distinguished from acromegaly by the fact that in the former there is symmetrical and general growth all over the body; the cranium grows as much as the facial bones, and the face does not look too large for the head, nor the head too large for the body, as is the case in acromegaly. In gigantism the ends of the bones are not enlarged out of proportion to the size of the shaft, and the hands and feet are not enlarged out of proportion to the arms and legs. The bones increase in length as well as in width and thickness, and that symmetrically, and the whole growth of the body is in proportion, as in a normal individual, all of which is quite the contrary of what is observed in acromegaly. In erythromelalgia, a vasomotor neurosis of the extremities, there may be some increase in the size of the hands and feet with severe pain, and there is always an impaired blood flow, giving burning sen- sations, local redness, and even cyanosis, often in patches or spots. There is, however, no enlargement of the bones or soft parts of the face, no eye symptoms, no marked change in the speech, and the hand itself is unlike the acromegalic hand; the fingers are not sausage-shaped, but smaller at the tip than at the base. Elephantiasis Arabum is a hypertrophic disease of the skin and subcutaneous tissue, located generally in one, occasionally in two extremities of the body. There is generally a history of several attacks of local inflammation of the part affected, followed by a con- tinuous growth and hypertroph}' of the skin, until an enormous size is reached. In elephantiasis the bones are not enlarged, the skeleton is not affected, and the nervous, facial, and cerebral phenomena of acromegaly are not present. Leontiasis ossea is the name given by Virchow to the condition in which osteophytes, or bony tumors, are formed on the face and cranium. These bony tumors are of irregular distribution, and produce great deformity and asymmetry. There is no hypertrophy of the extremities. During the first stages of acromegaly one of the fre- quent symptoms, and often a prominent one, is joint pain, which at this stage might lead one to mistake the disease for chronic rheumatism. The joints at this time are tender to the touch, but are not reddened or swollen. The pain is not permanent in any one or two joints, and ankylosis does not take place, although later crepitations are often present, and some con- tractures of the fingers may be found, due to the flexor tendons not growing as rapidly as the bones. As soon as the hands, feet, or face begin to enlarge, the diagnosis from chronic rheumatism becomes plain. Syringomyelia is a disease of the nervous system which generally begins before twenty, or in early adult life, and in its slow development and long dura- tion simulates acromegaly. After the complete development of either disease, however, the amyo- trophic paralysis, with retention of tactile and loss of thermic and painful sensation in the case of the syringomyelia, and the enlarged extremities in the case of the acromegaly, render the diagnosis easy. Several cases of acromegaly have shown coincident symptoms of syringomyelia, and autopsical examina- tions have revealed gliomata in the spinal cord. Rachitis is a disease of childhood, or rather baby- hood, occurring most frequently in -children under three years of age. This alone would exclude the possibility of confusion with acromegaly. The ends of the bones, especially the epiphyses of the wrist, are enlarged in rickets, while the hands and feet may be flattened and apparently widened, but there is no in- crease in the thickness of the hands or feet. The bones of the head show no malformation, except flattening and lengthening of the cranium with pro- jection of the occiput and the softened spots. This causes the cranium in rickets to appear too large for the face, while in acromegaly the face appears too large for the cranium. Softening of the ribs causes a sinking in just before the junction with the cartilages, giving the formation of the rachitic rosary, which from another cause we also find in acromegaly. Ky- Hi: REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Acromegaly phosis, when it occurs in rachitis, is in the dorsal region, while in acromegaly it is almost invariably in the cervicodorsal region. The diagnosis between the osteitis deformans of Paget and acromegaly is shown in the following table: Ostein* Deformans. 1. Rarely occurs before fifty, never before forty years of age. 2. The long bones are the ones primarily affected; rarely arc (he hands or feet affected. 3. The long bones are often curved, giving great deformity. 4. Often one lirub or one bone is affected long before another limb or bone. 5. The cranial hones are af- fected, rarely the facial. 6. The lower part of the face id narrow, giving it a triangular appearance. Acromegaly. 1. Very generally begins before forty years of age, almost never after fifty. 2. The hands and feet are enormous; long bones are gener- ally not affected much. 3. The long bones are normal in shape, possibly thickened at the extremities, but are never curved. 4. The hands, feet, arms, and legs are generally nearly sym- metrical. .",. The facial bones are affected, rarely the cranial. 6. The lower part of the f is broad, giving it an elliptical ap- pearance. In arthritis deformans decided changes take place in the articular tissues, and are accompanied by pain, with sooner or later great deformity and ankylosis of the joints. Tender nodules may appear in the muscles, while the muscles themselves become atrophied. The disease is apt to attack the same joints on both sides of the body symmetrically, but soon spreads to all of the joints. The hands are thin from the wasting of the fat and muscles, but the ends of the phalanges and metacarpal bones may be enlarged and nodular. The fingers are more or less flexed and turned toward the ulnar side of the arm, while the joints of the hand are all stiff and more or less completely ankylosed. Schulz has re- ported a case of acromegaly associated with arthritis deformans. Pulmonary hypertrophic osteoarthropathy is subse- quent to, or consequent on, some affection of the lungs, which may be a bronchitis, an empyema, or perhaps most frequently some new growth located primarily or secondarily somewhere in the respiratory tract. The hands are enlarged, but principally in the joints and the ends of the fingers, the middle of the hand not being attacked. The elbow, shoulder, and knee joints are all affected, and there is always more or less im- paired motion. The wrist joint is large, the hand proper not much enlarged, while the fingers are in- creased in size, especially the last phalanx, but the soft parts are not hypertrophied. The appearance of the finger nails is also quite characteristic of this disease. They appear too large for the fingers, spread- ing out at the sides, and even curving over the ends of the fingers, often giving the appearance of the beak of a bird, while the enlarged ends of the fingers have caused them to be likened to "drum-sticks." Local hypertrophies are not instances of partial acro- megaly. These local enlargements of one extremity, or one finger, or one toe are generally congenital, though they may increase in size at the time of puberty. One side of the face may be affected, in- volving the bones and soft parts, including the tongue, tonsil, and palate on that side, but whatever the enlargement there is no symmetry. Adiposis dolorosa is characterized by an enormous deposit of fat, first in the form of nodules, either in one location or in corresponding places on the upper or lower extremities. These deposits soon cause pain, diminished sensibility, and muscular weakness, and the muscles may show the reaction of degeneration. The absence of any marked enlargement of the hands, feet, and face, as well as the absence of increased bone growth, excludes confusion with acromegaly. Prognosis. — The duration of acromegaly is vari- ously estimated from ten to twenty years. The patient may die of some intercurrent disease, or may live for years with but a slow progression of the disease, but no case of complete recovery has yet been reported. This disease is one of continuous progression, espe- cially in the growth of the bones. Under treatment, or without treatment, periods of apparent quiescence or periods of cessation of symptoms occur, and the soft parts of the hypertrophied portions of the body not only may not enlarge, but may actually appear to be diminished in size. Yet even in such cases the bones apparently continue to grow. These periods, when the patient may say that he feels well, are sooner or later followed by marked exacerbations of all the symptoms, often coming on suddenly. Finally, little by little the patient falls into a con- dition of progressive cachexia, with partial or nearly complete loss of muscular power. This condition may last for several years, and then death occurs unexpectedly and suddenly from syncope. It is possible that an enlarged pituitary body may cause coma and death. Most subjects of acromegaly, however, die of some intercurrent affection, the most frequent of which are cardiac disease, nephritis, or diabetes, all of which are the results of the connective- tissue hyperplasia of the involved organs, viz., heart, kidney, or pancreas respectively. Treatment. — This disease is incurable, but in any given case we can safely expect to ameliorate many of the nervous symptoms. When there is an exacer- bation of symptoms, of all treatment rest is the most important, under which all the phenomena, except those produced by actual lesions, will improve. Pain, the most frequent cause of complaint, has been vari- ously treated by all of the analgesics, but with only temporary and varied success. The bromides are often of service in relieving the headache and the feeling of pressure in the head. The constipation should be treated, while dyspepsia, when present, can be best helped by a diet that re- quires but little mastication, as prognathism, which is so frequently present, is one constant cause of the dyspepsia. Any tonic treatment, combined with rest, will often cause a cessation of the acute symptoms and an appa- rent pause in the disease, except in the last stages. If there is atrophy of the muscles with great loss of muscular power, strychnine, given by the mouth or hypodermically, is of value, especially when com- bined with faradism. Cardiac insufficiency and renal insufficiency should be treated as though they were primary diseases, without regard to the acromegalic condition. The treatment of glycosuria should be cautious, i.e. the true diabetic diet should be assumed with care, if at all. If diabetes is present, the patient might be fed on pancreas, as in acromegaly diabetes seems to be generally, if not always, of pancreatic origin. The specific treatment of acromegaly undoubtedly must bear some relation to the secretion of the pitui- tary gland. During the stage of almost imperceptible, gradual, and perhaps symmetrical growth of the bones, pituitary feeding would probably be of no benefit, and might even aggravate or precipitate unpleasant symptoms, such as headache. But when a case of acromegaly comes into our hands for treatment the hypophysis disease has progressed far enough to give nervous symptoms and selective enlargements so typical of the disease. At this time we are probably having a diminished amount of normal secretion or a wholly or partially perverted secretion from the hypophysis. At this time pituitary substance will, I believe, often be found of marked benefit. In a case of acromegaly I have obtained good results from pituitary tablets, the dose varying from six to 103 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES twelve grains a day. In this case the headache, which had been continuous for two years, was mark- edly relieved. While under the treatment the appe- tite improved, the muscular weakness disappeared, the nervous restlessness subsided, and the patient was able to do her usual work, which she was not able (o do before the use of the pituitary substance. Also, tin' hypertrophy of the soft parts of the face, hands, and feet greatly diminished. On stopping the treat- ment, the headaches and muscular weakness again developed. In cases in which the thyroid gland is pathologically so changed that it cannot furnish its normal secretion, as denoted by mild myxedematous symptoms, the feeding of thyroid extract has been of some benefit. Little benefit has been derived from drugs. Arse- nic has been given without effect, but apparent im- provement has been noted in a few cases under treatment with potassium iodide; possibly there was a luetic element present in these instances. Oliver T. Osborne. Actinomycosis. — This disease is a combination of abscess formation and new growth of connective tissue. In most cases the disease has the character of a subacute or chronic suppurative process, but in some cases the new growth of connective tissue may be so marked a feature of the process that it may present the character of a tumor or neoplasm. The disease affects man and certain domestic animals, particularly cattle, in which it is probably best known. It has a wide geographical distribution. In cattle it most commonly affects the jaw bones, where it may take origin in the medulla or the peri- osteum, and may lead to the tumor-like conditions which have been long known as medullary sarcoma or osteosarcoma of the jaw, or as "lumpy jaw," etc. The external soft parts about the jaws and face, the tongue, the peripharyngeal tissue, the stomach, the skin, and the subcutaneous tissues in various places, may also be the seat of the disease. Anatomically, the lesions consist in general of an overgrowth of granulation and connective tissues, throughout which are distributed, more or less numerously, small, yellowish, soft suppurative areas or abscesses. If the seat of the lesions be the jaw, there is usually more or less new growth of bone as well. In swine the mamma?, the peripharyngeal tissues, the vertebra', and the spleen have been observed to be the seat of the disease. In horses the disease may occur in the spermatic cord after castration, as well as in the jaw bones and in the bones of the extremities. A few cases of the disease have been observed in dogs. In man the disease is probably more common than is generally supposed. It most frequently affects the tissues in and about the oral cavity, the pharynx, and the neck. It also frequently affects the lungs, the bones of the thorax, and the intestinal tract. Almost any organ or part of the body may become the seat of the disease. Anatomically, actinomycosis in man is essentially a destructive suppurative process accom- panied by a new growth of connective tissue which in general is not as abundantly developed as in the disease in cattle, so that in man the tumor-like lesions are less frequent. Pathology — The disease is due to the action of a vegetable parasite upon tissues which are suitably sus- ceptible. This parasite is an organism closely allied to the bacteria, but belonging to a higher class. Itoccurs in the lesions, and in the discharges from them, as small aggregations or colonies, of variable size, which in most cases are visible to the naked eye as grayish or yellowish granules or lobulated bodies, less than one millimeter in diameter. The presence of the peculiar granules in the lesion or in the pus is characteristic and diagnostic of the disease. As a rule they are soft, and when placed on a slide and covered with a cover 104 glass, they are flattened or crushed by the weight of the latter. In some instances, especially in cases in cattle, they may be more or less calcified. Under a low magnifying power a granule crushed beneath a cover glass will appear as an aggregation of lobulated hyaline masses, with rounded, finely serrated borders which may have a slightly brownish tint. In some instances a fine radial striation may be made out at the margins. As a rule masses of pus cells will be found surrounding the hyaline masses and making up a portion of the bulk of the granules. Under a higher magnifying power the hyaline material in places will have the appearances of being made up of a dense feltwork of delicate filaments having the Fig. 32. — Portion of the Margin of an Actinomycotic Granule crushed under a cover glass, as it appeared under a moderately high magnifying power. Various forms and appearances of the "clubs" are shown. « diameter of bacilli of moderate size and closely packed together. At the margins these filaments" usually have a radial arrangement, and some of them project beyond the limits of the hyaline mass. In the case of some granules, the margin of the hyaline mass may be formed of a row of closely set, elongated, finger- shaped, or club-shaped, or bulb-shaped bodies, com- posed of a hyaline substance and arranged radially (Figs. 32 and 33). These bodies constitute the so- called "clubs" or "rays" on account of which the name "ray fungus" has been applied to the parasite. They are of variable size and width, often being three or four times the width of the filaments. In stained preparations a stained filament may often be seen in the median portions of the "clubs" or "rays," which for this and other reasons are regarded as modifica- tions of the marginal filaments (Fig. 29). These bodies are usually better developed in granules from old than from recent lesions. If one of the granules be broken up on a cover glass and suitably stained there will be seen on microscopical examination, tion, besides long filaments which branch, short rod- like or bacillus-like or coccus-like forms (Fig. 30). These forms may be fragments of filaments or true bacilli and cocci growing in intimate association with the specific microorganism as secondary infecting elements. Such secondary infection of the lesions by bacteria is quite common. Microscopically, the lesions consist of larger or smaller abscesses, each containing one or two of the granules or colonies, and bounded by connective tissue, in all grades of development (Fig. 3(i). In the latter, giant cells may be present. A granule in a section stained by Gram's method appears as a mass REFERENCE HANDBOOK OF THE MEDICAL SCIENCES AcromcKaly of filaments embedded in a hyaline material and .-.bow- ing at tlic margin more or less radially arranged fila- ments, or the ••clubs" or " rays" previously described (Figs. 33 and 36). The hyaline material seems to be composed in many instances of non-staining degener- ated filaments. In other instances the nature of this hyaline material is not clear, but it is very probably the result of degenerative processes in the colony. It is not uncommon to see bacillus-like fragments of the organism in or among the pus cells surrounding the colony. jr. • f % • * M -. ^ § ^. • & m ''fa** •> f '^ J*.H ft . * Fig. 33. — A < rranule or Colony of Actinomyces, in a section about two micromilli meters thick, showing the "clubs" with central fil- aments at the margin. The general structure of the colony is shown also. From an abscess in the heart in a human case. X750. The pathological significance of the granules in the lesions of the disease was first clearly shown by Bollinger in 1877, although their presence had been noted previously by several observers whose work was incomplete and did not receive general recognition. Bollinger regarded the granules as growths of a fungus and as the essential cause of the disease. Harz, a bota- nist, confirmed Bollinger's ideas of their fungous nature and called the organism ''Actinomyces bovis," a name that has clung to it ever since. The disease in man was first recognized and identified as due to the same cause as that found in the disease in cattle by Ponfick a short time after Bollinger's publication. The granules, however, had been seen in a suppura- tive process in the neighborhood of the vertebrae in man by Langenbeck in 1845, and had been described and figured by Lebert in his " Atlas of Pathological Anatomy," published in 1856. Many untrustworthy observations have been published concerning the cultural peculiarities of Actinomyces bovis. It is commonly stated in text- books that culture methods have shown that various pathogenic species of this parasite are known, but the writer considers that the observations upon which these statements are based are open to serious question. It is the writer's opinion based upon his own obser- vations and those of others, that but one species of Actinomyces is the specific infectious agent of actinomy- cosis. This microorganism was first described by Woltf and Israel in 1891 and has been isolated from many cases of the disease since thai time l>y various workers [vide V. Harbitz and N li. Grondahl, Am. ./. Med. Sci., September, 1911). It grows on certain of the ordinary culture media in the form of masses or colonies of closely [lacked branching filaments resembling its colonies in the tissues. It grows best al body tem- perature but does not grow at all at ordinary tem- peratures. The characteristic "clubs" may be de veloped in colonies placed in sterile blood serum, as has been shown by the writer. By the inoculation of guinea-pigs and rabbits in the peritoneal cavity with cultures of the micro- organism, nodular lesions may be produced which have the characteristic microscopical appearances of the lesions of actinomycosis and the inoculated cul- ture material forms the characteristic "club-" bearing colonies or granules. It is not known whether the disease can be produced experimentally in cattle and other animals. This species of branching microorganism has been confused with certain other similar microorganisms which are widely distributed in the outer world and some of which occasionally have been found in inflammatory processes. These differ from it so markedly in certain ways that the writer thinks that the}' should be classed in a separate genus, and that cases of infection by them should not be called actinomycosis. Fig. 34. — A Cover-glass Preparation Made from a Granule. Some rods and branching filaments in association with pus cell are shown. X 1,000. The most frequent seat of primary actinomycosis in man is the tissues about the buccal cavity and the neck. Primary actinomycosis of these parts forms more than half of all the recorded cases. Next_ in frequency is primary actinomycosis of the digestive tract and of the lungs. Primary actinomycosis of the outer skin, exclusive of the skin of the face and neck, is less frequent. Various cases have also been recorded of actinomycosis of various organs, including the brain, 105 Acromegaly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES without any demonstrable primary lesion in the situa- tions above mentioned. The infecting organism is probably frequently carried into the tissues along with foreign bodies, especially such as occur in food material in the ease of cattle. The not infrequent finding of such foreign bodies in or near the lesions of the disease, and the observations of the increase of the disease in herds of cattle when a change has been made in their food, as also the very frequent localization in the neighbor- US . ■'•< Fig. 35. — Section of a Portion of an Actinomycotic Lesion in the Liver of the Same Case as That Mentioned in Fig. 29. The abscess, containing a "colony" or "granule," and the surround- ing connective-tissue growth extending into the liver sub- stance, are shown. The "colony" appears as a rounded, dark mass in the right upper quadrant of the figure. Low magnifying power. hood of the mouth, pharynx, etc., support this idea. The facts that it does not grow at the ordinary tem- perature of the air but best at body temperature and that no one has ever satisfactorily demonstrated its occurrence outside of the body, suggest that it is a natural inhabitant of the gastrointestinal tract as are certain of the pathogenic bacteria such as the pneu- mococcus. The demonstration by F. T. Lord of the frequent occurrence in carious teeth and in tonsillar crypts of microorganisms very closely resembling it, is strongly in favor of this view. The widely accepted teaching that its natural habitat is on grains and grasses is based on faulty knowledge of its biological characters and is erroneous. There is no satisfactory evidence that the infection may be transmitted from animals to man or from one individual to another. Actinomycosis in man is distinguished from the disease in cattle not only by a less extensive new formation of connective tissue, but also by its greater tendency to the formation of fistula? and sinuses, by which the disease may extend widely from one organ to another. Such sinuses may extend from the tissues about the mouth or pharyngeal cavities deeply into the thorax and along the spinal column (prevertebral phlegmon). In actinomycosis of the lungs fistula) may perforate the chest wall or go through the dia- phragm into the abdominal cavity. In actinomycosis of the intestines fistulae may form which usually perfo- rate the anterior abdominal wall; they may, however, extend through the lumbar region or into the rectum or bladder. The disease may also extend metastat- ically through invasion of the blood stream by the organism, and in this way various organs at a distance, such as the heart, brain, kidneys, etc., may become the seat of the disease. Only rarely does it spread by the way of the lymphatics. Secondary infections with pyogenetic cocci may occur. The clinical course and prognosis of the disease depend upon its extent and localization, and upon the occurrence of secondary infections with the pyogenic cocci. The last mentioned is an unfavorable com- plication. In extensive involvement of internal organs there may be fever and marked disturbance of nutrition. The cases in which it is localized about the buccal cavity or neck may be cured by surgical treat- ment, but recurrences after apparent cures are frequent. The bones of the jaw are rarely affected in man. The occurrence, in the soft parts of the neck or cheek near the jaw, of hard swellings which have arisen painlessly and present a fluctuating or suppu- rating focus, should excite suspicion of actinomycosis. Actinomycosis of the lungs in general resembles chronic pulmonary tuberculosis. The affection may last for months or years. It is characterized by cough, ■ ■ - ^»" V y ; ■T&t- ^£ jE» -* &$*?^£t» ,•$& ' , Fig. 36. — A Colony of Actinomyces in a Section of the Same Lesion as in Fig. 29. This is a colony composed of filaments and hyaline substance. There are no "clubs." X 500. by much sputum, which is often fetid or bloody, and by marked pains in the breast and back. There are also irregular fever and progressive emaciation. Fistula? perforating the chest wall and involving the sternum or ribs are not infrequent. In this the disease differs radically from tuberculosis of the lungs. The prognosis is generally bad. Remissions with appear- ances of healing occur. The process may be localized in any part of the lungs. It usually appears as small abscesses or bronchopneumonia patches, from which 106 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Active Constituents of Plants cavities may be formed accompanied by new growth of connective tissue. Actinomycosis of the intestines is characterized by extensive induration due to a marked development of peritoneal adhesions and to the extension of the proc- ess to the abdominal wall and neighboring organs. \, before mentioned, the tendency to the formation of the fistula' is marked. Metastatic involvement of the liver is not unusual. The prognosis must be regarded as unfavorable in general. Actinomycosis of the skin, according to Leser (Archil* f. klin. Chir., 1899, xxxix.), may appear as a circumscribed ulcerated lesion or as a nodular forma- tion with central cicatrizations. The subcutaneous tissue may also be affected and a chronic phlegmonous condition be produced. I ine of the forms of the disease known as "Madura foot" is very probably actinomycosis of the part. This is the so-called "white" or "ochroid" variety, in which the characteristic granules in the lesions are of this color. The "black" or "melanoid" variety of "Madura foot" is due to an altogether different vegetable parasite, which is a hyphomycete (Wright: Transactions of the Association of American Physi- cians, 1S9S, Journal of Experimental Medicine, vol. Hi., 1898). The diagnosis of actinomycosis is made by finding the characteristic granules or colonies of the organism in the lesions or in the discharges from the same. These in some instances may be so obscure as to escape observation with the naked eye. Microscopic exami- nation is necessary to distinguish the colonies or granules from small pieces of necrotic tissue and masses of pus cells. The pus or suspected material should be spread on a piece of glass. In this way the granules will be more easily seen. In actinomycosis of the lungs the organism may be found in the sputa and in the discharges from fistulas in the wall of the thorax. In the sputum the parasite is to be distinguished from the common leptothrix of the mouth by the fact that the filaments of the latter are larger, straighter, and thicker and do not branch as do the filaments of actinomycosis. The leptothrix filaments are also frequently adherent to epithelial cells. The treatment of actinomycosis should be operative if the extent of the disease admits of it. In internal treatment good results are said to have been obtained from the use of potassium iodide. The photographs which accompany this article were made by Mr. L. S. Brown and the writer, in the Clinico-Pathological Laboratory of the Massachusetts General Hospital. James Homer Wright. Actinomyxida. — An order of protozoans in the class Sporozoa. These animals consist of a double cellular envelope, three polar capsules, and eight spores arranged in ternary symmetry. There are four genera, mostly parasitic in annelid worms. See Protozoa. A. S. P. Active Constituents of Plants. — If this term were strictly interpreted, we should omit from consideration all but those constituents which produce positive physiological effects, other than nutritive, upon the animal system. As this treatment would exclude some substances having important medical and phar- maceutical relations, especially the latter, it is deemed better to consider briefly all plant constituents which affect the properties or uses of drugs or medicines. _ Of the nutrients proper, the albuminoids may be dismissed as of neither medicinal nor pharmaceutical importance in the department of materia medica. The sugars, inulin, starch, and cellulose, as well as the more important plant acids, are considered in their respective alphabetical order. The other principles of interest to us may be conveniently divided into the inorganic and the organic. The inorganics from this source are not treated as of importance in tin- modern materia medica. The vegetable compounds of iron, being readily assimi- lated are probably worthy of much more study and rational employment than has been accorded thorn heretofore. Sea, weeds have long been a well-known source of iodine, ami some vegetable drugs apparently owe their properties largely to this element. For the rest, the value of the inorganics in drugs depends chiefly upon the presence, especially in such fruits as prunes and tamarinds, of the well-known laxatives salts, the properties of which do not differ from those of inorganic origin. It is possible to obtain important cutaneous stimulant effects from the use of many vegetable substances rich in needles of cal- cium oxalate, although the fact has never been duly appreciated. The organic constituents which here require atten- tion are the vegetable acids, gums, fixed oils, resins, volatile oils, amaroids, glucosides, alkaloids, and en- zymes, together with such mixtures as oleoresins, gum-resins, and balsams. Vegetable Acids. — The number of vegetable acids which have been extracted from plants is very great, though only a few are found widely distributed among different plants. In the plant they serve a variety of useful purposes. Some of them, at least, act as reserve foods, being manufactured during darkness and consumed in the light, while the reverse is true of starch. They combine with organic and inorganic bases, which are thus rendered soluble and trans- portable. They render many fruits more palatable, thus influencing dissemination, and, on the other hand and in other cases, by their irritating or anti- septic properties they protect the plant against its enemies. Those which are of a resinous nature are thus particularly useful in preventing fermentation and decay (see Resins). Another class form an essential element in the composition of fats and are known as fatty acids (see Fixed Oils). Some of the vegetable acids, as tannic, citric, benzoic, and hydro- cyanic, are of direct use as medicinal agents, while others are of pharmaceutical interest, as influencing the extraction of the associated .substances. It has been claimed in numerous instances that a basic organic substance is more efficient when administered in combination with its iiatural acid. Many of the natural compounds of these acids are with the inorganic constituents, and it is these salts which chiefly render some fruits and vegetables laxative. The antiseptic properties which render many acids of value to the plant are made to render a similar service to man. The acid properties of the vegetable acids are much weaker than those of the inorganic acids, so that they yield up their bases to the latter. They are also less corrosive and irritating than the latter, and they often cannot perform the same service in digestion. Taken continuously or in excess, they can impair digestion or cause gastritis, and they are supposed to favor a rheumatic diathesis. Their salts are commonly more soluble than those of the inorganic acids. Their in- compatibilities are in general the same as those of the latter. Gums are supposed to exist as waste substances in the plant. They usually form in successive layers upon the inside of the cell wall — the process known to botanists as "mucilaginous degeneration." While these statements are true of those gums which are collected as such for medical and pharmaceutical uses, another class, occurring in such drugs as althaea, apparently act as reserve foods. These are of interest as affecting pharmaceutically the prepara- tions of drugs. The gums are insipid, insoluble in alcohol or ether, but soluble in water to form a 107 Active Constituents of Plants REFERENCE HANDBOOK OF THE MEDICAL SCIENCES mucilage or an adhesive jelly. They differ in their precipitation tests, but are mostly precipitated by lead acetate and by alcohol. Their presence in an alkaloidal solution will very often prevent the pre- cipitation of the latter by tannin and by weak solu- tions of metallic salts. Chemically, the gums are compounds of special acids with potassium, calcium, and magnesium. Medicinally the gums are inert, but they serve to form a protective covering in many cases, thus guarding against irritation, as in corrosive poisoning. When used externally for this purpose, some antiseptic substance should be added. Muci- laginous substances are highly prized in the making of poultices, because of their marked power to retain heat and moisture. Here, also, it is desirable to add an antiseptic. Peclosc, the mucilage-like or gelatinous constituent of such fruits as apples and pears, and of such vege- tables as turnips and beets, acts pharmaceutically like mucilage, being soluble in aqueous extracts, but precipitated upon the addition of alcohol. The gelatinous principle of sea weeds shares the properties of gum and pectose, and exists in very large percentage. Fixed oils, or fats, as those oils are called which are solid at ordinary temperatures, are compounds of special acids, known as fatty acids, with glycerin. From the names of these compounds those of the acids are derived, as oleic acid from "olein," stearic acid from "stearin," palmitic acid from "palmilin." Many fats are mixtures of such compounds. In the plant, fats are stored in parenchymatic tissue in the cell cavity. As they are reserve foods, of special use in the developing embryo, we find them specially characteristic of seeds, stored in both endosperm and embryo. They have a characteristically smooth feeling to the touch, are not volatile or inflammable, but combustible, insoluble in water, rarely soluble in alcohol, and then but partly so (see Castor and Croton Oils), but are soluble in volatile oils, ether, and chloro- form. Heated with or kept mixed with alkalies, they are decomposed into their glycerin, which is left free, and their acid, which unites with the alkali to form soap, the process being known as "saponification." On exposure to the atmosphere, they undergo a peculiar decomposition known as rancidity, giving them a very disagreeable odor and taste. Physiolog- ically, they are important nutrients, of exceptional value because of their ready absorbability through the skin, especially when rubbed upon it. They are not dialyzable, but by the aid of an albuminous substance and of gum they are resolved into an extremely finely divided state of suspension known as an "emulsion," and, more or less of this change taking place in the intestine, they can then become absorbed. They act as protectives, and, by their lubricating and softening power, as laxatives, whether taken internally or per rectum. It has been suggested that if taken in large quantities, the glycerin set free by their saponification in the duodenum acts as a laxative also. They readily dissolve a great number of substances, and become thus of the greatest use pharmaceutically, as vehicles. This use is the more important because of their great absorbability, which favors the absorp- tion of many dissolved medicinal substances used externally and internally. This property has to be considered in poisoning, as some poisonous substances not naturally absorbable from the intestine may be so under their influence. Fats are naturally destruc- tive to insect life, apparently by clogging up their breathing apparatus. They therefore exert an important action as parasiticides and increase the activity of other agents of this class. For similar reasons, they are efficacious in destroying ascarides. The medicinal effect proper of fixed oils is very slight, if we except a few like castor and croton oils, which are apparently complex substances and contain 108 an irritating element. The same is probably true of toxicodendrol, the poisonous fat of poison ivy and its relatives. Resins. — These are in some respects like the fats, in others like the volatile oils. They are solid, non- volatile and non-inflammable, but fusible and com- bustible. They are insoluble in water, but most readily soluble in volatile oils; frequently also in alcohol, fixed oils, ether, and chloroform. They are acid in nature and are saponified by alkalies, giving us a series of resin soaps. Nitric acid converts them into a peculiar substance resembling tannin. They are apparently, at least for the most part, waste substances in the plant, which transports them through its tissues dissolved in volatile oils, as liquid oleoresins, in which form they are stored in special lacuna 1 , ducts, or tubes. They are of use to the plant by rendering its food storage parts antiseptic and disagreeable, or even dangerous, to animals eating them. Pharmaceutically, the resins are very trouble- some, as they are dissolved in the alcohol in the extraction of many drugs, and are then most easily precipitated upon the addition of water, and often of acid substances. As to their medicinal properties and uses, the resins, by warming, become adhesive and have numerous and important uses depending upon this property. Those which are little irritating can be used as protectives, upon the evaporation of their solutions painted upon the surface. They are more or less antiseptic; less so than volatile oils. They are usually more or less irritant, many being thus available as counter-irritants. One class of them exhibit this irritating property especially in the intestine, and become purgative, some very power- fully so. Among these may be mentioned those of jalap, scammony, podophyllum, leptandra, iris, and euonymus. Preparations of such drugs should be thoroughly subdivided through an excipient, so that no large particle shall lodge in a pocket of intestine and produce undue irritation. Gum-resins are merely mixtures of gum with resin, which adapts them very well to being used in the form of emulsions. Not only do the relative percentages of gum and resin vary widely in different gum-resin-, but the percentage is quite variable in different lots of the same. The activity is, of course, proportional to the percentage of resin. Important gum-resins are myrrh, asafetida, ammoniac, elemi, galbanura, and gamboge. They occur also in many drugs, such as sumbul, angelica, parsley, and lovage. Volatile oil is a very common constituent of gum-resins. Volatile Oils. — For the sake of long custom and convenience, these are treated as a class of active constituents, although the idea is not a scientific one. They are in reality mixtures which are very indefinite in kind, as well as in degree. The name may without impropriety be extended to all volatile and aromatic constituents of plants. They consist mostly of one or more oxygenated compounds mixed with one or more hydrocarbons, usually terpenes. Of these, the former is commonly the active one. Since volatile oils are rather irregular in the relative amounts of the active and the inactive portions, and also highly subject to adulteration, which is very difficult of detection, the use of {he active constituents, the purity of which is readily ascertained, is much prefer- able to that of the oil. Doubtless such use will extend as these facts become more generally appre- ciated, and this result will be hastened by a more common custom of regarding and speaking of these oils as indefinite and irregular mixtures, a custom which is carefully followed in this work. Their chief use to the plant is perhaps as solvents of other constituents. Their nutritive relations are not well known, and if they were, they could not be easily defined, owing to their variable chemical nature. Their fragrant properties are undoubtedly of value in indirect ways, such as attracting insects. Their REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Active Constituents of Plants antiseptic properties and the obnoxious character of many of them to some animals undoubtedly serve a protective purpose. They may be found in any part of the plant, perhaps most frequently in the seed. They may often be seen in the leaf, in the form of pellucid dots, when viewed against the light. Owing to their volatile nature, drugs which depend upon their presence are very liable to deteriorate on being kept, and unusual care has to be exercised in their preparation and preservation. On this account they are usually dried in the shade. These substances leave no greasy stain on paper. They are light, volatile, aromatic, and inflammable. They dissolve in water sufficiently to render the latter aromatic and somewhat medicinal. They are readily soluble in alcohol, fixed oils, and glycerin, and act as solvents of resins, fats, and many medicinal sub- stances. Aside from their medicinal properties, they have a wide use within as well as outside the bounda- ries of pharmacy, in odorizing and flavoring. In their physiological and medicinal properties, volatile oils agree in some characters and vary greatly in others, so that they fall naturally into different therapeutical classes. Their local stimulant properties are very general. This makes them counterirritant; some of them, like oil of turpentine, very powerfully so, especially when confined under an air-tight covering. Others which are strongly counterirritant are those of mustard, amber, erigeron, cinnamon, cloves, and camphor. The irritating effect of some volatile oils is followed by a local anesthesia, occasionally quite strong, as in the case of menthol and oil of cloves. In line with their counterirritant action may be con- sidered their stomachic and carminative properties, which are perhaps more general than any others. Here again certain oils, especially those of the families Umbelliferse (anise, fennel, caraway, etc.) and LabiataB (mint, thyme, pennyroyal, etc.), excel others. As to their gastric effects, it is to be noted that their presence with the digesting food mass tends to inhibit the process. This action also is greater in the ease of certain oils, and is said to be quite wanting in that of oil of peppermint, which is thus an excep- tionally valuable carminative. Aside from their intestinal effects in stimulating secretion and peris- talsis, they exert a strong action in stimulating the sympathetic nerves, thus overcoming the excessive relaxation upon which various forms of serous diarrhea depend in whole or in part. This action effects a final result similar to that of the true astrin- gents, and makes a combination of volatile oils and astringents highly effective. Their carminative prop- erties render them of great use in combining with griping purgatives. Their antiseptic properties are quite general and strong, though they vary greatly in degree in the different oils. They act not only as direct germicides, but they stimulate the cells them- selves in their fight against the foreign organisms. In general, the oils of the family Jlyrtacese and many of those of the Lauraeeae are thus antiseptic, as are those of birch, wintergreen, sandal, copaiba, and thyme. Oil of cinnamon is probably the most power- fully antiseptic of any, eucalyptol, if pure, perhaps standing next. Volatile oils agree in their strongly diffusive properties, on account of which their systemic effects come on quickly. If the vapor is con- fined, they are quickly absorbed, even through the skin, as they are by inhalation. They then become systemic stimulants, though overdoses may act as depressing poisons. This stimulation makes them antispasmodic in many cases. Elimination begins as promptly as absorption, and their local effects are again seen at the point of excretion. They vary in their selection of the channel of excretion. Some, like eucalyptus, copaiba, and cubebs, have a tendency toward the respiratory mucous membrane and become important stimulating and antiseptic expectorants. Others, like sandal, copaiba, cubebs, birch, winter- green, turpentine, juniper, savin, tansy, and buchu, have an affinity for the kidney, and become stimulat- ing (to irritating) and antiseptic diuretics, some important antiblennorrhagics. A few, like oil of chenopodium, are powerfully anthelmintic. Those especially adapted to perfuming and flavoring may be named as orange, lemon, bergamot, rose, bay, bitter almond, citronella, lavender, nutmeg, and cinnamon. Oleoresins, being resins dissolved in volatile oils, naturally combine their properties. They very often, however, contain a third substance in addition, and this may give to them specific properties distinct from those of either the oil or the resin, and in some cases exceedingly powerful. The most important oleoresins in use are those of the male fern, capsicum, ginger, copaiba, black pepper, cubeb, turpentine, and hops. Other important oleoresins contained in drugs but not commonly isolated for use are those of calamus, iris, inula, prickly ash, mezereum, and stillingia. Balsams are liquid or solid oleoresins depending in part for their properties upon the contained benzoic or cinnamic acid, or both. Their properties are readily deduced from this composition. The principal ones are benzoin, dragons'-blood, tolu, and peru. Copaiba, though commonly so called, is in no sense a balsam. Amaroids (their Latin names ending in "inum," their English in "in"). — This term has been proposed for those bitter extractives of plants which, having a definite chemical composition, do not belong to any of the recognized classes of proximate principles. While not highly scientific, the term is often very convenient. Glucosides (their Latin names ending in "inum," their English in "in"). — These are compounds of glucose with some other substance, the latter class covering a wide range and occasionally containing nitrogen. They are especially numerous in the Liliaeeae, the Apocynaceae, and some other families, but are very widely distributed elsewhere. They act as reserve foods to the plant, and are therefore more abundant in those parts which act as storage reservoirs, and at the close of the growing period. The bodies associated with the glucose are very fre- quently poisonous or obnoxious, subserving thus a protective function, while the glucoside in this way also acts as a protective of other parts or constituents. Owing to the readiness with which they are decom- posed (in the plant by special enzymes), their nutri- tious portion is readily available and at once assim- ilable. For the same reason they constitute very unstable medicinal agents and, like drugs contain ing them, require to be treated with great care in pharmaceutical operations. They are mostly soluble in both water and alcohol. Some, like amygdalin, are inactive until such decomposition occurs, while others may be thus rendered inactive. Such decom- position is effected by the action of dilute acids, especially if heated, by hot water, and by the pro- longed action of alkalies. They are mostly precipi- tated by tannin and lead acetate, and very frequently by mercuric chloride. They are usually very ener- getic physiological agents, but their actions are too diverse for generalization. It may be said, however, that they are as a class more disposed to act upon the circulation than in any other one direction. Several of the glucosides are widely distributed among differ- ent plants, and, exhibiting variations among them- selves, may be regarded as forming sub-classes. Tannin or tannic acid (elsewhere considered) is technically a, glucoside, but differs so much from the others that it is difficult to regard it as such. The saponin group (see Saponin) have also distinct and important properties. The chief interest in glucosides as a group centers in their incompatibilities, as indicated above. The principal glucosidal drugs are as follows: 109 Active Constituents of Plants REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amygdalin. Emodin or relatives. Saponin or a similar body. Bitter almonds, Peach seeds, Wild cherry. Cherry laurel, Peach, plum, and cherry leaves, etc., Buckthorn, cascara sagrada, and other species of Rhamnus, Aloes, Rhubarb, Srnna, Apocynum — apocynin and apocynein. Convallaria — convallamarin and couvalhirin Digitalis — digitalis and others. Dulcamara — dulcamarin. Phytolacca — phytolaccin. Piper — piperin. Soap bark, ^ Soap root, Euonymus, Senega, Caulophyllum and others, J Squill — scillin and others. Black mustard — sinigrin. White mustard — sinalbin. Strophanthus — strophanthiu and strophanthidin. Alkaloids (their English names ending in i/ic, their Latin in ina, although it is now proposed to abolish this most convenient distinction and to spell them with a final in, a practice actually now in use to a great extent in Germany). — These are nitrogenized organic bases, occurring in plants (also in animals) usually, if not always, as waste products, and in combination with acids. Although commonly waste products from a nutritive standpoint, they perform the most useful purposes in the plant economy. Usually poisonous and intensely bitter, they often serve to protect those parts of the plant which are used for food storage from consumption by animals. They may occur in any part of the plant, but are most often found in the seeds, leaves, and bark of both stem and root. They are characteristically common in some families, like the Rubiacea?, while from others, like the Compositae, the largest of all families, they are nearly or quite absent. Alkaloids are usually crystallizable. Many were formerly known only in a liquid or amorphous state, but many of these, when thoroughly purified, have since been found crystalliza- ble. Those which are not so, yet usually yield salts which are. Some alkaloids are volatile. Many alkaloids, while acting as proximate principles them- selves, readily separate, either in the plant by natural processes or under laboratory treatment, into other alkaloids and some associated substance, so that series of them are formed. These are necessarily of unstable chemical composition. In some cases, an alkaloid will result from the decomposition of a glucoside, as solanidine from solanin. Alkaloids differ greatly in solubility, but the strong tendency is toward solubility in alcohol and insolubility in water, while of their salts the reverse is true. A few which vary markedly from this rule are enumerated below. These bodies show their basic nature by turning red litmus paper blue, but more especially by uniting with acids to form salts. They do this without dis- placing the hydrogen of the acid, as metals do. They vary greatly in the intensity of this affinity for acids, some, like caffeine, being very feebly basic. In some cases we are even uncertain whether they can properly be classed as alkaloids. Alkaloids are as a class prob- ably the most active physiological constituents of plants. Their actions are so dissimilar that they can- not be at all generalized, except to say that by their almost invariably bitter taste they act, in the absence of other antagonistic properties, as bitter stomachics and tonics. In many cases two alkaloids, the one a derivative of the other, occur in the same plant, with antagonistic properties. Alkaloids converted into methyl compounds are thus usually antagonistic to those so yielding them. It is of the utmost importance that the prescriber should keep in mind the incompatibilities of alkaloids. Some of these incompatibilities are innocent, or can even be utilized in important ways. Thus the addi- tion of acids converts alkaloids into salts, which may then be dissolved in water, the physiological prop- erties being usually unaltered. These salts differ greatly in solubility. In most cases acetates are the most soluble, hydrochlorides next, and sulphates the least. In other eases, a physical incompatibility exists, so that the alkaloid is precipitated. Owing to their energetic action such a result is exceedingly dangerous, the first portions of the medicine being ineffective, the last portions poisonous. In this connection it may be stated that all salts which will turn red litmus paper blue will precipitate aqueous or weak alcoholic solutions of alkaloidal salts. Svich solutions are almost always precipitated by alkali hydrates, soluble salicylates, benzoates, iodides, and bromides, tannic acid, chlorides of mercury and of gold. The presence of. mucilage or hydrated starch will sometimes prevent this precipitation, especially th.it by tannic acid. In other cases incompatibility involves the destruction of the alkaloid. Oxidizing agents will usually accomplish this result, except when they enter into a saline combination. This fact is utilized in some cases of antidotal treatment, as of morphine by potassium permanganate. Chloral hydrate is incompatible with many alkaloids, forming a soft or liquid mass. The solanaceous alkaloids, of which atropine is the type, as well as aconitine and confine, are decomposed by alkalies. The strength of many drugs can be readily standardized by de- termining the average percentage of alkaloid con- tained. The principal drugs which depend upon alkaloids for their activity are the following: Aconite (aconitine). Aspidosperma (aspidospermine, a mixture of six). Belladonna (atropine). Berberis (berberine). Coffee (caffeine). Cannabis indica (?). Chelidonium (chelerythrine and chelidonine). Cinchona (quinine, cinchonine, and cinchonidine, chiefly). Coca (cocaine). Colchicum (colchicine). Conium (confine). Ergot (?). Gelsemium (gelsemine and gelseminine). Granatum (pelletierine). Guarana (caffeine). Humulus (trimethylamine, partly). Hydrastis (berberine, hydrastine, and [artificial] hydras tinine). Hyoscyamus (hyoscyamine and hyoscine). Ipecac (emetine and cephaeline). Lobelia (lobeline). Menispermum (berberine and menispine). Nux vomica (strychnine and brucine). Opium (many, the principal being morphine, codeine, narcotine, narceine, and the artificial deriva- tives apomorphine, apocodcine, and heroine). Physostigma (physostigmine or eserine). Pilocarpus (pilocarpine and pilocarpidine). Piper (piperidine, partly). Sanguinaria (sanguinarine, chiefly). Seoparius (sparteine, partly). Spigelia (spigeline). Staphisagria (four alkaloids, the properties not w r ell differentiated). Stramonium (daturine, a mixture). Tobacco (nicotine). Veratrum (veratrine, a mixture). Important alkaloids which are soluble in water are confine, codeine, caffeine, nicotine, atropine (nearly four grains to the ounce), pelletierine, lobeline (considerably). 110 REFERENCE HANDBOOK OF TFIE MEDICAL SCIENCES Acupuncture Alkaloids which, with their salts, are little solu- ble in ordinary alkaloklal solvents arc morphine, trigonelline, etc. Enzymes, 'rinse are vegetable ferments, acting like the animal ferments, pepsin, trypsin, etc., in de- composing or digesting nutrients for the use of the plant. There are different classes of them, each act- ing upon a certain class of nutrients. The diastases acting on starch have become extensively utilized in medicine, but most enzymes have not. One class has for its function the decomposition of glucosides, another the digestion of amaroids, another acts upon certain gums. Like pepsin and others of its Class, the vegetable enzymes cannot be extracted in a pure condition nor can their composition be determined. II. II. Rusby. Actuarius, John. — Very little is known about the life of Actuarius beyond the following few facts: He practised medicine during the thirteenth or fourteenth century, and was attached to the Court at Constantinople. He wrote treatises on the princi- ples of therapeutics, on the composition of various remedial agents, and on the urine as an aid to diagno- sis. He is systematic in his manner of treating these subjects and his style of writing is clear. Among Greek medical authors he is the first to mention the milder purgatives like cassia, manna, senna, etc. Editions of his treatise on urine were published in Venice (1519), Basle (1520), Paris (1522), and Utrecht (1(170); and a collection of his entire works, in two volumes, was issued in Paris in 1556. A. H. B. Acupressure. — A procedure devised by Sir J. Y. Simpson, of Edinburgh, in 1859, for arresting hemor- rhage from a vessel by means of pressure made bj r a needle transfixed through the neighboring tissues. The flow of blood through an artery may be arrested in any one of three ways. The vessel may be simply compressed between the needle and some firm tissue, as a bone or the in- tegument, as repre- sented in Figs. 37 and 38. When the artery lies embedded in a soft tissue, as in a divided muscle, its occlusion may be ac- complished by tor- sion. This is done by- introducing the nee- dle on one side of the vessel, and, when it has passed through a portion of the tissue, twisting it around the artery, and fixing its point in the tissue in a direction opposite to that in which it was first entered; or the artery need not be included in the bight of the needle, but the latter may be turned before reaching the vessel, the latter then being com- pressed by the elastic force of the twisted tissues acting upon the needle. A third method, applica- ble also in cases in which the vessel lies in a yield- ing tissue, consists in pressure between the needle and a slip-knot. The needle is passed beneath the artery, and a loop of fine wire is slipped over its point, the ends of the loop passing over the artery, and being fastened by two or three turns over the shaft of the needle (see Fig. 39). In the case of small vessels, the needles may be withdrawn at the expiration of twenty-four hours; but when large arterial trunks are occluded, the pressure should be maintained for forty-eight hours at least. The advantages claimed for this method are: the ease and rapidity with which the needles may be applied, no delay being caused in the operation; the absence of danger from Suppuration of the ends of the divided vessels; and non-interlerenee with rapid clo- sure of the wound, no inflammation being excited by the presence of the needles in the tissues for so short Fiq. 39. a period of time. These advantages, however, are less manifest at the present time, since the intro- duction and general employment of antiseptic liga- tures, and it is not likely that the procedure will ever again enjoy the popularity which it at one time possessed. T. L. S. Acupuncture. — An operation which consists in the introduction of needles into the body, either as a means of giving exit to the fluid in edematous tissues or for the relief of pain in neuralgia and muscular rheumatism. It is a method in great vogue in China, and is used by the physicians of that country not only to assuage pain, but to promote reparative action in ulcers and in the treatment of various other affections. It is said to have been introduced into Europe from China by the missionaries in the seventeenth century. The instrument employed is a round polished needle, having a cylindrical handle of sufficient size to permit of its being readily manipulated by the fingers. It is introduced into the tissues by a quick rotatory movement, and is then left in situ for a number of minutes, or even for an hour. Sometimes the inser- tion of a single needle is sufficient to relieve the pain, but ordinarily half a dozen or more are employed. This little procedure may be practised almost pain- lessly, and is sometimes wonderfully effective in con- trolling neuralgic and rheumatic muscular pains. It often fails, indeed, and it seems impossible to deter- mine beforehand in what cases it will prove service- able, but certainly no case of lumbago or sciatica should be abandoned until acupuncture, as well as the more ordinary remedies, has been tried. In anasarca, when the scrotum and lower extremities are distended with fluid, the patient may experience comfort from a few punctures with a three-cornered surgical needle. The operation should be practised with caution, however, as it is apt to excite an ery- sipelatous inflammation of the integument. In the treatment of paralysis insulated needles are some- times used as a means of introducing the electric current into the deeper tissues. This procedure has received the name of electropuncture. There is another form of acupuncture, called Baun- scheidtismus, which at one time enjoyed a great popular reputation, and which even now is not very infrequently employed. It was devised by Carl Baun- scheidt, a German mechanic, who is said to have con- ceived the idea from observing that the irritation caused by the bites of insects afforded him consider- able relief from the pain of an articular affection from which he was suffering. The instrument employed consists of a cylinder enclosing a button into which are inserted from twenty to thirty short needles. The open end of the cylinder is placed on the integu- ment, and then by means of a handle the button with needles attached is drawn up into the cylinder com- . pressing a spiral spring: when the handle is released the force of the spring impels the needles suddenly 111 Acupuncture REFERENCE HANDBOOK OF THE MEDICAL SCIENCES and sharply into the skin. The operation may rest here or an irritating fluid, such as mustard water or cajeput oil, may be applied to the punctures. This is employed for the relief of neuralgia and musculai pains, and often proves of very great service. There is still another form of acupuncture, if such There is <» it can be called, though it is more nearly related to hypodermic medication. It consists in the hypo- dermic injection of pure water, and has received the name of aquapuncture. Many superficial pains, even though quite severe, may be relieved by this simple procedure. That the relief thus obtained is not merely the effect of imagination, is evidenced by the fact that neuralgias of distant parts are not benefited by aqueous injections, but in order to be effectual the operation must be practised at a point as near as possible to the seat of pain. The Schlerich method of local anesthesia is a form of aquapuncture, the strength of the cocaine solution commonly employed being in- sufficient to account for the complete anesthesia pro- duced. Aquapuncture has been employed in various forms of neuralgia, in lumbago, and in painful func- tional affections of the abdominal viscera. Bartholow claimed to have obtained excellent results from the injection of water into the substance of paralyzed and atrophied muscles. From 2 to 4 c.c. (4 to 1 dram) of fluid may be used for each injection, and the opera- tion may be repeated if no relief is experienced at the expiration of two or three minutes. (See also Anesthesia, local.) T. L. S. Acystina. — A group established by Sambon to include those protozoans in Hartmann's tribe Bmu- cleata in which "the ookinete remains free and does not become encysted." It includes two families: HcemoproteidcB and Leucocytozoidce. See Protozoa. A. to. x. Adamantinoma.— This is a variety of neoplasm rather frequently found in the lower jaw, and more rarely in the upper. It develops from the remains of the enamel-organs, hence its name, adaman- tinoma, or adenoma adamaiitiiuim as it is sometimes wrongly called, since it has nothing to do with glands. It consists of cords and masses of epithelial cells resembling in structure the fetal epithelial buds that form the teeth. The stellate cells in the central portion of these epithelial masses may form true enamel, but they often degenerate and undergo liquefaction, thus giving rise to the formation of multiple cysts. When the cysts are large and numerous the growth often assumes the character of a multilocular cystoma. The tumor is essentially benign and closely related to the odontoma with which it may be associated. The most common site for both of these neoplasms is at the angle of the lower jaw in the neighborhood of the molar teeth. It is probable that these neoplasms are both the result of disturbance of development of the teeth. The writer has seen a similar tumor replacing the hypophysis in a case of dystrophia adiposogenitalis. In this loca- tion the adamantinoma must be regarded as a teratoid tumor arising from remains of the craniopharyngeal duct. Aldred Scott Warthix. Adams County Mineral Springs. — Adams County, Ohio. Post-office. — Mineral Springs, Ohio. Access. — Via Cincinnati, Portsmouth and Vir- ginia Railroad to Mineral Springs station, thence four miles by carriage to Spring hotel and cottages. Con- veyances can also be had at Rome (on the Ohio River) for the Springs. These springs, the medicinal properties of which were recognized by the Indians, are two in number and flow about sixty gallons of water hourly, having a temperature of 56° F. They issue from the base of a high hill and are surrounded by picturesque and charming scenery. According to a partial analysis by Prof. E. S. Wayne, the water of Spring No. 1 is highly charged with gas and contains 205.35 grains of sol'id matter per United States gallon, composed as follows: Magnesium chloride, calcium chloride, cal- cium sulphate, calcium carbonate, sodium chloride, iron oxide, and iodine. The water may be classified as a saline calcic with ferruginous properties. Spring No.2. In- 1.000,000 Parts there are: Magnesium sulphate 10S ■ U Sodium sulphate 65.41 Calcium sulphate 56.00 Sodium chloride 16. *9 Potassium chloride 3 . 69 Ferrous carbonate trace. Total mineral matter 250.00 Free acid as sulphuric 19.60 The accommodations for visitors are now very sat- isfactory, the hotel having been enlarged and a num- ber of cottages added. The location affords a pleasant retreat for those who seek respite from the cares of business or need the refreshing influences of rural scenery and air. The water has long been used by persons suffering from affections involving the stomach, bowels, kidneys, and liver. Emma. E. TA alker. Adams, William. — Born in London, England, on February, 1, 1820. He studied at Kings College, and afterward held successively the following positions: Pathological Prosector in St. Thomas' Hospital, in 1S42- Assistant Surgeon (in 1851) and, later (in 1857), Surgeon in the Royal Orthopedic Hospital; Instruc- tor in Surgery in tlie Grosvenor Place Medical School, in 1854; Surgeon in the Great Northern Hospital, in 1S55- and Surgeon in the National Hospital for Paralytics and Epileptics, in 1874. His death occurred February 3, 1900. Adams was a prolific contributor to medical liter- ature The following are the titles of some of the more important of his writings: " A Course of Lectures on Orthopedic Surgery," 1S.55— 1858; "On the Repara- tive Process in Human Tendons after Division, 1.S60; "On the Pathology and Treatment of Club-foot (awarded the Jackson Prize by the Royal College of Surgeons in 1866); and "On the Treatment of Dupuytren's Contraction of the Fingers, and on the Obliteration of Depressed Cicatrices by Subcutaneous Operations," 1879. A - H - B - Adams, Sir William.— Born in Cornwall, England, in 1700 He began the study of medicine under a practitioner in Barnstaple and at the age of seventeen went to London where he became a pupil of Sam at the Moorfields Eye Hospital. After practising for a time as an oculist he suddenly acquired fame by the publication of a work on Egyptian ophthalmia, which was then endemic in the British army in which he advised treatment contrary to that followed by Saunders and others connected with the London i.ye Infirmary. This led to a polemic in which he accused his opponents of attempting to prevent the rational treatment of that disease. The quarrel made con- siderable noise, but he triumphed and won the favor of the Court, being appointed oculist to the prince Regent, afterward George IV and to the latter a brother the Duke of Sussex. He was later knighted and the position of ophthalmologist to the Greenwi 1 Hospital for invalided soldiers and sailors was created for him The members of the regular medical stan 112 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adaptation were however, incensed at this appointment and .soon procured the abolition of the office. Adams receiving a grant of £4,000 as compensation for his discharge. Thereafter his life was uneventful and was passed in the enjoyment of a large and lucrative practice. A few years before his death, in order to ,,,,.,. i the conditions of a large legacy, he took the name of his wife, Rawson. He died at Albemarle In I ebruary, 1829. , . , . . _ t . In addition to his polemical writings on Egyptian ophthalmia, the most important of Adams' contri- butions to medical literature are: "Practical Obser- vations on Ectropion or Eversion of the Eyelids, with the Description of a New Operation for the (in,, of that Disease" (since known as Adams' operation), 1*1-'; "A Practical Inquiry into the Cause of the Frequent Failure of the Operation for Depression," etc., 1817; "A Treatise on Artificial Pupil," etc., 1819. T. L. S. Adaptation. — If we think of life, as most of us do, herently a process of adjustment of relations to r relations, clearly adaptation is the most univer- sal of vital events. A complete denotation of the term for Medicine would comprise much of the chem- istry, anatomy, and physiology underlying the whole profession. Still, one thinks of adaptation more nat- urally as an adjustment of structure to function or to other structure than in the opposite phase of adap- tation of function to structure. In other words, pur- pose is the ultimate meaning of organism, the ever- changing purpose expressed only in properly adapted structure and for which indeed the structure exists. Any other view seems to involve the thinker at once or else ultimately, sooner or later, in a dilemma which convicts the human mind, inherently and character- istically rational, of irrationality. Function, then, purposiveness, is properly considered primary to structure, and adaptation becomes a series of changes in protoplasm; and it is thus that the term is com- monly understood. The ulterior causes of organic adaptations we may find set forth at any length almost in the discussions of the determinants of evolution by the old-time Dar- winians (selectionists) on the one hand and by the mutationists (disciples of DeVries and Mendel) on the other. Adaptations are at once the causes and the results of this principle of unrollment or progress which we designate as evolution. Many other re- searchers than these of course have elaborated our knowledge of the influences exerted on an organism by environment, notably Buffon, Lamarck, Geoffrey, while DeVarigny in his book called "Experimental Evolution" has collected a large number of examples of variation or adaptation. C. B. Davenport's " Ex- perimental Morphology" discusses many of the char- acteristic adaptative reactions of animals and plants, while T. H. Morgan's "Evolution and Adaptation" has an illuminating account of the most broadly bio- logical relations of the theory of the subject we are discussing. From the last-mentioned book we may quote two of many useful paragraphs: "In regard to the perpetuation of the advantages gained by means of this power of adaptation" (for medical science, one of the most salient aspects of the subject), "it is clear in those cases in which the young arc nourished during the embryonic life by the mother, that, in this way, the young may be rendered im- mune to a certain extent, and there are instances of this sort recorded, especially in the case of some bac- terial diseases. Whether this power can also be transmitted through the egg, in those instances in which the egg itself is set free and development takes place outside the body, has not been shown. In any case, the effect appears not to be a permanent one and will wear off when the particular poison no longer acts. It is improbable, therefore, that any permanent contribution to the race could be gained in this way. Vol. I.— S Adaptations of this sort, while of the highest im- portance to the individual, can have produced little direct effect on the evolution of new forms, all hough il may have been often of paramount importance to the individuals to be able to adapt themselves, or rather to become able to resist the effect of injurious substances. The important fact in this connection i- the wonderful latent power possessed by all animals. So many, and of Mich different kind-, are the sub- stances to which they may become immune, that it is inconceivable that this property of the organism could ever have been acquired through experience, no matter how probable it may be made to appear that this might have occurred in certain cases of fatal bacterial diseases. And, if not. in so many other cases, why prevent a special explanation for the lew case How far-reaching and complex at once the relations of adaptation appear to be, as we have already said, far beyond all present explanation, is suggested in the following sentences also from Morgans treatise, it being noteworthy that they seem to express this authority's opinion on this matter as well as that of the writer whom he quotes: "Niigeli's wide experi- ence with living plants" (protoplasm is one appar- ently in alga and in man) "convinced him that there is something in the organism over and beyond the influence of the external world that causes organisms to change; and we cannot afford, I think, to despise his judgment on this point, although we need not follow- him to the length of supposing that this inter- nal influence is a 'force' driving the organism forward in the direction of ever greater complexity. A more moderate estimate would be that the organism often changes through influences that appear to us to be internal, and while some of the changes are merely fluctuating or chance variations, there are others that appear to be more limited in number, but perfectly definite and permanent in character. It is the latter, which, I believe, we can safely accredit to internal factors, and which may be compared to Nageli's 'in- ternal causes,' but this is far from assuming that these changes are in the direction of greater completeness or perfection, or that evolution would take place in- dependently of the action of external agencies." From this point of view adaptations with which the medical man is most apt to be concerned (and when is he not concerned with some or other adaptations!) must be deemed as much determined from within, perhaps in the inherent metabolism of the organism, as from without in the immensely complicated physio- chemimental environment. In other words, the changes of an adaptive kind that occur in human beings appear to be alan gebraic balance of energies or at least tendencies without and within the person- ality — forces acting upon but never wholly controlling the bodily nature of man, in a broad sense. Among the varieties of adaptation discussed by Morgan (loc. cit.) are sex, instincts, form, symmetry, degeneration, protective coloring, length of life, secondary sexual organs, individual adjustments, growth, atrophy, reactions to poisons, and regenera- tion. In the broad range of practical medicine many other phases of adaptation will doubtless occur to the reader, most of them, but by no means all, useful to the individual. Many of these adjustments to con- ditions outside of the organism w : ould more naturally be thought of perhaps as the "effects" of certain "causes," yet at the same time obviously they are steps taken by the self-protective living protoplasm toward meeting new conditions. Thus, for example, the undersize of underfed children, while properly a result of too little food (and especially, perhaps, of too little protein) results in fact in an adaptation to the lack of sufficient food, a small, thin, weak inactive individual requiring somewhat less nutriment than one of the opposite characters of structure and habits. This illustration has its chief interest, however, in calling attention to the fact that adaptations are in 113 Adaptation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES reality effects whose causes in the total coordination of the living world often are far too complex to be detailed or in any degree described in this present early stage of human knowledge. One conspicuous aspect of adaptation for our immediate purpose, as elsewhere, is the advantagous- ness to the individual of wide and ample powers of adaptation to new conditions both useful and the reverse. By having this efficiency in a high degree the individual on the one hand can profit by favorable conditions in the physio-chemi-mental environment and, on the other hand, fail to suffer from or to succumb to those effects that are unfavorable. Peo- ple differ not a little in this respect, as is readily seen in the various and varying immunity of some persons and the susceptibility of others to infections. About the precise adaptations of the organism to these multivarious conditions we are of course just begin- ning to learn a little something — but so far that little certainly is not much. George V. N. Dearborn. Addison, Thomas. — Born at Newcastle-on-Tyne, England, in April, 1793. He received the degree of Doctor of Medicine from the University of Edinburgh in 1S15. Shortly afterward he was given the appoint- ment of House Physician at Lock Hospital. About 1820 he was received as a pupil at Guy's Hospital, London, and for thirty-seven years he retained a con- nection with this institution in one capacity or an- other, first (1824) as Assistant Physician; then next (1827) as Instructor in Materia Medica; and finallv (1S37) as full Physi- cian and as a co- lecturer with Bright on the Practice of Medicine. His dis- covery of the disease which bears his name (" Addison's disease") brought him a world-wide ce- lebrity. A master- ful description of this disease was pub- lishcd by him in 1855, under the title: "On the Con- stitutional and Local Effects of Dis- ease of the Suprare- nal Capsules," with plates. Almost equally meritorious are the papers on pneumonia, on pneumonic phthisis and on phthisis, which he pub- lished from time to time, in the Guy's Hospital Re- ports. His death occurred at Brighton on June 29, I860. A. H. B. Addison Mineral Springs. — Washington County, Maine. Post-office. — Addison, Maine. Access. — Via steamer from Portland. The spring is two and a half miles distant from the railroad station, Columbia Falls or Columbia Station on the Washington County Railroad. There is a good road to the spring. Hotel and private families accommo- date visitors. This spring is located in a charming hilly section within one-quarter of a mile from an inlet of the Atlantic and about one hundred feet above the ocean level. The ocean is nine miles distant. The beauti- ful Pleasant River is near by. The scenery in the neighborhood is charming. The spring which is boiling, is about five feet in diameter and four feet in depth, and has a steady, voluminous, and rapid flow. Tin' following analysis was made by Professor Hayes, State Assayer and Chemist, Boston, Massachusetts. v wi»W -• Fig. 40. — Thomas Addison. One United States Gallon Contains: Potassium sulphate . 60 grain. Sodium sulphate . 27 grain. Calcium sulphate . 52 grain. Sodium chloride 0.S9 grain. Sodium bicarbonate . 44 grain. Calcium bicarbonate 2.65 grains. Magnesium bicarbonate 1.12 grains. Iron bicarbonate 1 .65 grains. Silica and alumina traces. Total 8. 14 grains. The gases present are principally nitrogen, oxygen, and carbonic, acid with a little sulphureted hydrogen. According to the classification adopted by Dr. James K. Crook, this water is properly termed a light alkaline chalybeate. It has been used with apparent benefit in acid dyspepsia, renal congestion, skin affections, and other conditions in which a mild antacid diuretic is required. Emma E. Walker. Addison's Anemia. — See Anemia, Pernicious. Addison's Disease. — Synonyms. Bronzed Skin Disease; Melasma Suprarenale. Of the above terms the one adopted as the title is to be preferred, for while the peculiar discoloration of the skin is not an invariable characteristic of the affection, the credit of Addison to the discovery of the disease called by his name has never been called in question. Definition. — A disease characterized by progres- sive asthenia, digestive disorders, pain and tenderness chiefly seated in the epigastric, hypochondriac, and lumbar regions; and an abnormal pigmentation of the skin and mucous membranes. Historical Notice. — The first case of Addison's disease on record is to be found in Lobstein's treatise, " De nervi sympathici humani fabrica et morbis," Paris, 1823, from the English translation of which, by the late Prof. Joseph Pancoast, I take the following extract: "I have myself observed the nerves forming the suprarenal plexus much thicker in disease, where the capsular renales, which were more than twice aa large as usual, had degenerated into tuberculous sub- stance." The patient was an unmarried woman, twenty-five years of age, who died in " convulsive spasms analogous to the epileptic. ***** Noth- ing unusual was discovered in the body of this woman but the aforesaid change in the suprarenal glands, and the enlargement of the nerves." Notwithstanding the fact that there is no record of any darkening of the complexion, the above was undoubtedly a typical case of Addison's disease, in which, moreover, death by convulsions is not uncom- mon. The observation regarding the thickening of the nerves in this, the first recorded instance of the disease, is of remarkable interest. The second case was recorded in the "Halle Hospital Reports" by Schotte, in October, 1823, and republished in vol. vii. of the Deutsches Archiv fur klin. Med., by Risel, in the course of his article "Zur Pathologie des Morbus Addisonii." The third case came under the observa- tion of Richard Bright, at Guy's Hospital, in July, 1829. It is contained in Bright's classical "Reports of Medical Cases," and also figures as Case V. in Addi- son's original memoir. The lesions of the capsules were characteristic; there was no other affection of any consequence, and for the first time in the history of this disease it was noted that the "complexion w:is very dark." A few other cases were reported before the year 1S55, when Addison published his work " ( )n the Constitutional and Local Effects of Disease of the Suprarenal Capsules," but it was reserved for his sagacity to detect the relation between the well- marked constitutional symptoms of the affection, the peculiar pigmentation of the skin, and the structural changes in the suprarenal capsules. 114 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Addison's Disease It is no disparagement to the memory of Addison to say that the general acknowledgment of his discovery was retarded by his including in his treatise cases which, at the present day, would be rejected from the , egory of Addison's disease. Of his eleven eases there are but lour uncomplicated with other affec- tions, two complicated; while of the remaining five, one was a case of softening of the lira in with advanced kidney disease ami tuberculous deposits in various organs, among others in one suprarenal capsule, and tin' oilier four were eases of widespread carcinomat- deposit, the suprarenal capsules being more or less involved in each. Addison was evidently under impression that the symptoms of the disease were I ,. t he suppression of the unknown function of the adrenals, ami ih.it, therefore, any destructive lesion of the-.- bodies was capable of causing them. This view of the pathogenesis of the affection has been called in question by distinguished pathologists, who insisted on restricting the term Addison's disease to a tuberculous inflammation of the adrenals. The inal view of Addison, however, is resuming its sway and bids fair ere long to be generally adopted. A n ill be seen later on, the most reasonable theory of the pathogenesis of the disease is that of adrenal inadequacy. Etiology. — Age, sex, and occupation are promi- nent factors in the etiology of this disease. The lesion of the adrenals being, in the great majority of cases, tuberculous, it follows that the affection is most com- mon during those decades in which tuberculous proc- es prevail — i.e. between twenty and forty years < f age. Exceptionally, the disease may manifest itself both in adolescence and in old age, and it may even be Congenital. For example, Belyayeff has reported the of an infant born with a dingy yellowish-gray skin who died at the age of eight weeks. At the autopsy both adrenals were found in a state of cystic degeneration. The disease is much more prevalent in males than in females, and especially so among the laboring classes. Of 1S3 undoubted cases tabulated by < ireenhow, 119 were males and sixty-four females, and more than nine-tenths of the whole number were engaged in laborious manual work. Several cases have been associated with psoas or lumbar abscess, t'n.' adrenals becoming involved by extension of the inflammatory process. In others devoid of such spinal complication, the origin of the disease has been attributed by the patient to overexertion of the spinal muscles. Such was the fact in one of my own cases, the patient's first symptoms having been weakness and pain in the back immediately following the occupation of weeding her garden. In cases like those last referred to, it is probable that the lesion was well advanced at the time of the overexertion or trauma- tism, the latter merely serving to awaken dormant symptoms. Symptomatology. — To quote the words of Addison: " The leading and characteristic features of the morbid state to which I would direct attention are — anemia, general languor and debility, remarkable feebleness of the heart's action, irritability of the stomach, and a peculiar change of color in the skin, occurring in con- nection with a diseased condition of the suprarenal capsules." Taking these in order, the anemia first claims atten- tion. As is well known, it was while studying the disease which he termed idiopathic anemia, now more generally known as pernicious anemia, that Addison, as he expressed it, "stumbled upon" the discovery of the disease which bears his name. With his mind intent upon the disease which presents the profound- est grade of anemia, it was natural that Addison should attribute the languor and debility of the bronzed skin disease to a similar state of the blood. The anemia of that affection is, however, more apparent than real. In one of the most typical cases on record, described and pictured by Byrom Bramwell in his atlas of clin- ical medicine, theredcorpu cles numbered 3,250,000, while the hemoglobin was present "in at least the norma] amount." In another case of dis- tinguished clinician the red corpuscles numbered 3,500,000 per cubic millimeter, i.e. seventy Jier cent, of the normal. These figures certainly do Dot repn a high gi ideoi anemia. As to the leucocytes, the only change worthy of remark is a relative lymphocytosis. According to Dr. Wilkes, to whose vigorous and loyal efforts tin- general recognition of Addison's disease is perhaps chiefly due | Etolle ton), anemia is not a fea- ture of the disease. Under the microscope the red corpuscles are seen to be of normal size and shape, and to form rouleaux as in health, while the white cells may or may not be slightly in excess. In one or two cases free pigment granules are -aid tn have been present, but the observation stand- in urgent need of confirmation. Anemia not being present in sufficient degree to account for the profound asthenia of Addi- son's disease, to what then is it due? As will be seen under the head of pathogenesis, it is most reasonably to be attributed to an irregular distribution of the blood, to its accumulation in the enormous district of the abdominal vessels. The languor and debility or, in one word, the asthenia which, according to Addison ami all subse- quent observers, is a cardinal symptom of the disease, is also one of the earliest. In all histories of the disease the patient has been compelled to abandon his usual occupation by reason of muscular weakness, and when there is no complication with other wasting disease this prostration is unattended, at least in the early stage, with any marked diminution in the vol- ume of the muscular and adipose tissues. The power of resistance to depressing agents is greatly reduced. Mental and bodily exertion which would be regarded by the healthy as trivial, is followed by exhaustion, and the use of purgatives is positively dangerous. As remarked by Bramwell, in more than one of the recorded eases death has resulted from an ordinary dose of a purgative drug. With this asthenia there is enfeebled action of the heart, of which the apex beat is faint or imperceptible and the sounds weak and distant. Anemic murmurs are rare and the same is true of valvular defects, dilatation and hypertrophy. Edema is seldom observed. The pulse presents varying features, but is always weak and compressible. It may be frequent or infrequent, full or small. Patients are liable to attacks of collapse induced by vomiting, purgation, or other depressing cause, or without apparent cause, which may be so severe as to resemble the collapse of cholera. Contrary to the usual frequency of the pulse in collapse, a remarkable diminution in the number of the heart beats has been observed in several cases (Risel mentions seven), and this without any disease of the brain or important cardiac disease. In a ease reported by Cholmeley (Medical Times and Gazette, 1S09, vol. ii., p. 219) in which death was preceded by profound collapse, dyspnea, and con- vulsions, the pulse fell to thirty-six per minute. In advanced cases, the blood pressure is almost invaria- bly low and is not raised by coincident nephritis or arteriosclerosis. Pressures as low as seventy-five are recorded. Symptoms referable to disordered digestion are always more or less prominent and are of early appearance. Among them are marked anorexia, nausea and vomiting, constipation alternating with diarrhea, and epigastric tenderness. Sometimes the nausea and vomiting occur in paroxysms without any apparent exciting cause, and on this account, as well as because of their severity, they have been compared to the gastric crises of locomotor ataxia. Epigastric tenderness was a prominent feature of two cases that came under my care at the Episcopal Hospital of Philadelphia. In the report of the first I noted that "at times there was great tenderness about the 115 Addison's Disease REFERENXE HANDBOOK OF THE MEDICAL SCIENCES umbilical region, and on one occasion, after palpating the abdomen, the patient uttered loud cries for ten or fifteen minutes and seemed in great agony" (Trans. Path. Sue. Phila., vol. v.). In the other case, "the pain was latterly most severely felt in the left lumbar region, in which situation there was also a great degree of tenderness on pressure" (Trans. Path. Soc. Phila., vol. x.). In the first of these cases nothing was found at the necropsy to account for this remarkable tenderness; in the second, it might have been due to the great tumefaction of the lumbar glands. The date of the appearance of the pathognomonic discoloration of the skin, from which the disease derives one of its names, is very variable. It may either precede or follow the constitutional symptoms, or the disease may terminate fatally without its manifesta- tion. Greenhow has collected a number of cases illustrating the erratic appearance of this, the only pathognomonic feature of Addison's disease. In one of his cases the pigmentation of the skin is said to have been the sole symptom for eight years, at the end of which period the pigmentation deepened and the other well-known symptoms of Addison's disease were superadded. This case is the most remarkable on record in so far as the early appearance of bronzing is concerned, but it has been criticised by Brain well, who has shown that the original pigmentation, limited to the forehead and parts adjacent, was probably due to n the other hand, when the constitutional symptoms are well pronounced in a primary case, and the bronz- ing of skin is not yet developed, the diagnosis is to be made only, if at all, by the exclusion of other wasting diseases, especially cancer of abdominal organs and progressive pernicious anemia. Many years ago there came under my care at the Episcopal Hospital of Philadelphia a case of lumbar abscess with several open sinuses leading to carious vertebrae. The gen- eral surface of the body was of a dark dingy hue, and the orifice of each sinus was surrounded by a broad, deeply pigmented ring. The patient had been pre- viously at another institution, where secondary dis- ease of the adrenals had been suspected. The autopsy showed these bodies to be perfectly healthy and the kidneys to be involved in extensive amyloid degenera- tion. A dingy discoloration of the skin is not uncom- mon in amyloid disease of the kidney, as first pointed out by Grainger Stewart. The discoloration of skin, although not the most essential characteristic of the disease, is justly re- garded as its most important diagnostic feature. It is to be distinguished from melasma gravidarum, pity- riasis versicolor, lichen, and pigmentary syphilides, and this is readily done by any one familiar with these affections. The melanoderma of phthisical pa- tients presents more serious difficulty. Although the latter is often confined to the face and does not invade the mucous membrane of the buccal cavity, the ditfi- culty is a real one, and is augmented by the fact that pulmonary tuberculosis is the most frequent compli- cation of Addison's disease. The seat of the melasma suprarenale, or its greater intensity, upon the face and neck, the dorsum of the hands, areola of the nipple and about the umbilicus, in the axilla, groin, and upon the genitals, is characteristic. Other diagnostic fea- tures of the pigmentation have been described above under the head of Symptoms. A discoloration of the skin liable to be confounded by the inexperienced with that of Addison's disease is sometimes seen in badly nourished paupers of dirty habits, whose skin is the abode of vermin (vagabonds' disease). This pigmen- tation shows itself in the form of patches separated by healthy skin; the epidermis is often roughened, and the discoloration more marked upon the trunk than on the face and hands. The skin is also often marked with scratches, the result of the intense itch- ing. Under the microscope, the particles of pigment in this affection are found in all the layers of the epidermis, instead of being limited, as in Addison's disease, to the deeper layers of the rete Malpighii. The pigmentation of chronic malarial poisoning i- distinguished from that of Addison's disease not only by its distribution, but by the history of the case and the frequent presence of splenic enlarge- ment; chronic icterus, with which Addison's disease was formerly confounded, is distinguished by the presence of pigment in the ocular conjunctiva and in the urine. Other discolorations of the skin simulating closely the pigmentation of Addison's disease are mentioned by systematic writers, but are so rare as to be in them- selves pathological curiosities. Among them may be mentioned a diffuse pigmentation associated with chronic scurvy (Bramwell), and a few other cases of melasma occurring without obvious cause. Accord- ing to the author just cited, there are certain forms of pigmentation of the skin associated with chronic peri- tonitis, or malignant disease of the abdomen or pel- 118 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adenoma vis which it is impossible to distinguish from Addi- son's disease. This fact, though discomfiting to the clinician, is of great interest to the pathologist, as tending to prove that the most characteristic symptom of the affection, the melasma suprarenale, is to be attributed rather to the implication of the abdominal sympathetic than to that of the adrenals. Prognosis. — The prognosis is in the highest degree unfavorable, although recoveries of cases presenting every sign and symptom of the affection have been reported by the most competent observers. Among these may be mentioned Sir William Gull and Dr Finney. In making predictions as to the duration of life, the remittent character of the disease should be liiune in mind. A case seen during a period of exacer- I, 1 1 em may lead to the prognosis of a speedily fatal result, but the worst symptoms may disappear and be followed by a prolonged period of remission. The average duration of the life of hospital patients who, i rule, do not apply for treatment until forced to ;ekiio\vledge the fact of their illness, has been es- timated at two years. Sudden death without pre- ceding exacerbation is sometimes observed, the fatal result being apparently due to syncope. Treatment. — At the present time, there may be said to be a specific treatment of Addison's disease — that with adrenal extract. This fact, however, in no way diminishes the importance of general therapeutic measures, of which the most important are the fol- lowing: Cessation of work is the first thing to be insisted upon in the way of treatment, and during the exacerbations strict confinement to bed. An im- mediate mitigation of the symptoms has often fol- lowed the admission to hospital of a patient who, up to that time, had been endeavoring to resist the gradually increasing asthenia. A moderate amount of stimulants is generally well borne, but. cod-liver oil, which might seem appropriate on account of the tuberculous nature of most cases of the disease, is, as a rule, not tolerated. Remedies to allay irritability of the stomach are frequently indicated, such as ice, lime water, carbonic acid water with brandy, bismuth, creosote, hydrocyanic acid, and small doses of opium. Massage and faradization are well worthy of a trial in order to drive the blood from the abdominal vessels. Iron and arsenic should be employed ten- tatively and will be generally found useful, and the same is true of mix vomica and its derivatives. Cathartics are to be avoided, as profound depression has often followed their employment in this disease. When constipation is troublesome it should be relieved by enemata and suppositories. The diet should be simple but nourishing, consisting of soups, milk, eggs, meat jellies, koumyss, and the like. Treatment with Adrenal Extract. — The success that has attended the use of adrenal extract is such as to make it imperative in all cases of Addison's disease. This is not a mere obiter dictum, but is the result of a careful study of many of the reports upon the subject. A few examples will suffice to show the kind of evi- dence on which the administration of the adrenal extract is based. < isler (International Medical Magazine, February, 1890) reports a case in which there was marked im- provement under the use of the extract, attended with considerable gain in weight and restoration of general vigor. The pigmentation, however, which was of advanced grade, had not diminished except on the palate. A case is reported by Suckling (British Medical Journal, May 28, 1S9S) in which the symptoms and signs were well pronounced except pigmentation of mucous membranes, of which there is no mention. Tablets of suprarenal extract (aa gr. v.) were given to the extent of from twenty to thirty- five daily. In the course of a year recovery was complete with disappearance of melanodermic and leucodermic patches. Kinnicutt tabulated forty- «ight cases (American J ournal of the Medical Sciences, July, 1897) treated with adrenal preparations. "Six patients are reported as cured or practically well, twenty-two improved, eighteen unimproved, and in two instances an aggravation of the symptoms is tiled to have occurred during treatment. In the second class of eases, those in which improvement took place, the improvement was but temporary; but this was as much as could be expected, since in many the disease of the adrenals was associated with grave tuberculous lesions in other parts of the body. A scries of 120 cases, including ninety-seven previously collected by E. \V. Adams ( J'ractitioner, lxxii., 473, 1903) was analyzed by Sajous with ref- ference to the effect of adrenal preparations. In fifty-one the benefit was slight or nil, in thirty-six there was marked improvement and in twenty-five there was permanent benefit. The adrenal extrac- tives should not be administered in a haphazard manner. In one of the cases in which permanent benefit was the result of their administration, the dose was one-twelfth of a grain; in another, the initial dose of the extract was ten grains thrice daily and was gradually increased until 175 grains were administered per diem. The adrenal preparations should be given to meet certain indications of wdiich the most promi- nent are diminished blood pressure and hypothermia. When the temperature and the blood pressure are raised to the normal standard, the full effect of the remedy has been secured and is only to be maintained by a careful observation of the case and, perhaps, by occasional suspension or increase of the dose employed. As Sajous remarks with reference to the cases in which there was permanent benefit: "Although the remedy was used empirically it so happened, in all prob- ability, that the doses employed coincided with the needs of the organism." The most satisfactory preparation has been found to be the desiccated gland — glandulae suprarenales sicca?, U. S. P., the dose of which must be ascertained by tentative use with the aid of the thermometer and the blood pressure tests. The subcutaneous injection of adrenal fluid extracts is exceedingly painful and the active principles which they contain are rapidly oxidized and, it is believed, rendered inert during their absorption. On the theory that Addison's disease is chiefly due to suppressed function of the adrenals, the use of adrenal extract would find its most successful employ- ment in those cases in which the lesion consists of simple atrophy or fibroid degeneration. Frederick P. Henry. Adenitis. — See Lymphatic Glands, Diseases of. Adenoid Vegetation. — See Tonsils, Pharyngeal. Adenoma. — Adenoma (from aS-n", gland, and -oiua noting in pathology a swelling or tumor) is the term applied to a new growth originating in glandular epithelium and corresponding in histological structure with the general type of gland tissue. Every new formation of glandular tissue, every glandular hyperplasia, cannot be regarded as an adenoma, and sometimes it is impossible to say whether an apparent growth is a simple hyperplasia or a tumor. A gland which is increased in size in consequence of excessive nutrition and function can- not be called an adenoma, but must be considered a hyperplasia. In the same way must be considered those forma- tions in mucous membranes which frequently develop in consequence of chronic inflammation and take the form of tumors. These are local new formations which project above the surface in the form of polypi or papillary masses. The new growth commences in the 119 Adenoma REFERENCE HANDBOOK OF THE MEDICAL SCIENCES connective tissue, and the epithelium also takes part, in that, by the increase of the surface, the covering epithelium also must increase. If there are glands present their ducts are usually obstructed, and cysts are formed with papillary projections within them. This must be considered simply as a growth due to chronic irritation, and as entirely distinct from the true glandular polyp of the mucous membranes in which a formation of new glands actually occurs. Clinically, these can usually be distinguished for the simple polyp disappears when its cause, chronic irritation, disappears. Etiology. — The causation of adenomata is ob- scure though probably no more so than that of new growths in general. In some forms congenital misplacement of tissue ele- ments appears to play an important part. Thus in the kidney, adenomata sometimes are found which cor- respond in structure to the adrenal. These, as pointed out by Grawitz, develop from aberrant remnants of the adrenal embedded in the kidney substance. This is also true of adenomata correspond- ing to the structure of the mamma occasionally seen in the axilla, and of the rather unusual substernal tumors in which a tissue similar to that of the thyroid body is found. Here it is probable that the theory of embryonic remains of Cohnheim gives the true explanation: the tumor in each of these instances develops from embryonic fragments which become separated from the gland in its development. Although in certain locations, as the stomach and rectum, the adenomata appear to bear out Virchow's irritation theory, in other locations they offer it no support at all. The parasitic theory receives absolutely no support from the adenomata, for it is impossible to conceive of a vegetable or an animal parasite causing the re- production of definite gland tubules. Varieties and Structure. — The appearance of adenomata varies greatly with their location. Natu- rally any particular cell or arrangement of cells cannot be described as peculiar to this tumor, any more than any type of cell can be regarded as characteristic of all physiological glandular structures. The adenomata differ from one another in structure as much as the structure of the liver differs from that of the lacry- mal gland. In the stomach, intestine, and uterus, in a general way, the epithelial cells are arranged as tubular acini with a central lumen, the cells generally occurring in one layer, though there may be more. The acini are separated from one another by connective tissue in which the blood-vessels and lymphatics are borne. Why the cells in their growth should grow as tubules instead of breaking through the basement membrane and forming atypical groups of epithelial cells, as is seen in the form known as adenocarcinoma, is diffi- cult of explanation. It is probable that the inherent tendency thus to develop is not early influenced by their altered environment. That they do not break through and grow as carcinoma is frequently seen in some large and rapidly growing adenomata. The cells lining the tubules may be columnar or cuboidal, according to the gland from which the tumor develops. In addition to the tubular form there is an un- common variety, the racemose adenomata, in which the appearance is that of a complicated gland struc- ture with closely aggregated acini of circular out- line containing columnar, cuboidal, or polyhedral cells. Then, again, in the liver, kidney, and adrenal occur adenomata resembling more or less closely the normal structure of those organs. As in any other epithelial tumor, the relation be- tween the epithelial cells and the connective tissue varies. When the development of the connective tissue is excessive, far beyond that of the normal gland, it must receive some recognition in naming the tumor, for it is as truly new formed as is the epithelial portion: in such cases it is called an adenofibroma. When this connective tissue is especially abundant in cells and represents an embryonic tissue, the term adenosarcoma is used. In the ovary occurs an adenoma in which the acini line cyst cavities. This is termed an adenocystoma. Adenomata, as far as known, do not contribute to the body metabolism. That there is a partial preser- vation of function is occasionally seen. In the adenoma of the liver sometimes a biliary pigmentation occurs; in the adenoma of the breast there may be a secretion of milk-like fluid; in the adenoma of the intestine the tubules may contain mucus; in the ade- noma of the thyroid colloid material may collect. But these substances remain in the tubules in which they are formed, and take no part in the general metabolism. Secondary Changes. — All forms of degeneration are common in adenomata. Hyaline transformation may give the tumor an appearance justifying the term "cylindroma." This, however, is rare. Myxomatous and calcareous degenerations occasionally occur. Cystic change may result from gradual dilatation of the glandular acini. Hemorrhages are common, and on free surfaces ulceration is frequent. The most important change, however, is a carcino- matous transformation. This is especially common in the stomach, intestine, and uterus. The proliferation of the epithelial cells becomes excessive; the acini be- come more abundant and irregular; the cells depart from their tubular arrangement and grow as solid epithelial masses outside the acini, forming an adeno- carcinoma, or, as Ziegler named it, adenoma destruens. The growth may eventually become purely carcino- matous, but it usually retains more or less its adeno- matous type. General Character. — The rapidity of growth of an adenoma differs in various parts of the body in which it has its seat, and the same holds true for its malignancy. There are few which can be considered as strictly benign tumors. The pure adenoma seen in the liver may form metastases in the spleen and less frequently elsewhere. Fatal metastases from adenomata of the thyroid have been reported. In the sweat, sebaceous, and lacrymal glands the tumor usually grows slowly, remains local, and may be con- sidered benign. In some locations, although adeno- mata never produce metastases, they may endanger life by their size, as in the ovary; or may obstruct im- portant canals, as in the intestine; or may cause great disfigurement, as displacement of the eye in adenoma of the lacrymal gland. The general health may also be influenced by interference with the normal function of the organ in which they are located, or in conse- quence of ulceration and hemorrhage. There are few tumors more malignant than the adenomata of the intestinal tract. They extend rapidly, infiltrating all coats of the intestine, and frequently produce metastases in the liver. Their malignancy does not always depend on carcinomatous transformation, for some of the most destructive tumors of this canal are pure adenomata. As regards the terms Malignant Adenoma and Adenocarcinoma, it seems best to use the former in designating those growths in which, although there is extensive infiltration of surrounding tissue and eyen the formation of metastases, the tumor still retains its glandular type; and to use the term Adenocarci- noma for those forms in which the cells depart from the tubular arrangement with the formation of distinct cancerous areas. The principal locations in which adenomata may occur and brief descriptions of their characteristics dependent on location and origin are given below: Skin. — Adenomata of the skin are rare. They may develop from the sebaceous or from the coil glands. 120 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adenoma They crow slowly and are practically always benign. Adenomata of sweat glands are found in various parts of the body, bu1 principally on the face, where they are of a dirty grayish-white color with nodular surface. Histologically, coils of dilated duels arc seen, from which degenerated epithelium can be squeezed. Cam- piniri (1895) describes cystic and carcinomatous changes in such tumors. Adenomata of sebaceous Fig. 41. — Benign Adenoma of the Small Intestine. X 10 diameters. glands appear principally on the face and are usually of congenital origin. They appear as small, roundish, convex papules, of bright color, and in old people are often associated with fibromata. Whitnej' has described an adenoma of sebaceous- gland origin which was the size of an orange and con- led large cavities filled with a material resembling butter in "its color, consistence, and general appear- ance. (Consult also the special article on Adenoma of the Skin.) Mucous Membranes. — Mouth. — Adenoma of the mucous glands of the mouth is very rare. It occurs a- isolated nodes and in some cases gives rise to macro- cheilia. Adenomata of the salivary glands have been reported. Larynx and Bronchi. — A few cases have been reported of benign adenomata arising from the mucous glands of these organs. Eber (1.S96) has reported several cases in the bronchi of sheep. They occur as irregular nodular growths. Stomach and Intestine. — Small, apparently benign adenomata are sometimes seen. The malignant adenomata and the adenocarcinomata are the most important forms. They start as soft nodular growths which break down readily and ulcerate. They infil- trate all coats and may cause perforation. Metas- tases in the liver may occur, and there is sometimes a direct extension to adjacent organs, as from stomach to pancreas. In the large intestine, of all forms of new growth, this tumor is the most common cause of chronic intestinal obstruction. Histologically, they may be made up of dilated, irregularly branching tubules presenting a single layer of cylindrical epithe- lium — in the stomach originating from the gastric tubules, in the intestine from the glands of Licberkuhn; or in addition to this structure there may I"- irregular solid masses of epithelium, the result of great pro- liferation of epithelial cells and destruction of the basement membrane. In the large intestine the locations, in order of frequency, are the rectum, the sigmoid, splenic and hepatic liexures of tl Ion, and the cecum. In the small intestine adenoma i- occasionally found in the duodenum at the papilla marking the orifice of the bile duct. Vulva. — Benign adenomata arising from the glands of Bartholin] have been reported. Kelly describes an adenocarcinoma, as large as an oral of the vulvovaginal glands. / rinary Bladder. — Adenomata of this organ are rare. They may be sessile or pedunculated, smooth or lobular, benign or malignant. It is not easy to explain their origin. tJterus. — Adenoma originates generally in the body of the uterus, but occasionally in the cervix. It may rapidly infiltrate the myometrium and may produce nodules on the peritonea] surface. It has the usual glandular structure and a small amount of fibrous stroma. Carcinomatous areas may develop. Occasionally a benign polypoid adenoma may be seen, but it is often difficult to distinguish this from a hyperplastic glandular endometritis. Fig. 42.— M X le- diameters. Diffuse benign adenomyomata of the uterus have been carefully described by von Recklinghausen and Cullen. Adenoma in Solid Viscera. — Liver. — Adenomata of this organ are rare. They may occur in the normal or in the cirrhotic liver, and appear as small, grayish- white, reddish, or brown miliary solitary or multiple areas. They are made up of tortuous, branching, gland-like tubules of newly formed trabecular of liver cells, not arranged as typical liver lobules. The cells 121 Adenoma REFERENCE HANDBOOK OF THE MEDICAL SCIENCES are large, pale, and finely granular. They arise from proliferation either of liver cells or of the cells of the bile capillaries. The larger ones have a distinct capsule. Some writers believe that they may become carcinomatous. Another and rare form is the adenocystoma, which is made up of cysts containing a colorless fluid, the walls of the cysts being covered by glandular epi- thelium. This form probably originates from the bile ducts. Fig. 42, a. — Malignant Adenoma of the Rectum. Greatly magni- fied in order to show character and arrangement of the newly formed glands. Kidney. — Congenital adenoma, struma aberrata suprarenalis. — As shown by Grawitz, this tumor develops from fragments of the adrenal body which in the development of the kidney become incorporated in its substance. The tumor is small, grayish, and generally just beneath the capsule. Histologically, it consists of large pale epithelial cells arranged in tubules similar to those of the cortical portion of the adrenal. The cells are filled with fat granules. Active proliferation may occur with tendency to malignancy. The observations of Askanazy and Lubarsh indicate that malignant tumors resembling carcinomata may develop from these growths. Adenomata arising from renal tubules are rare. They originate in the convoluted tubules, and appear as very small nodular masses, though they sometimes may reach a diameter of three to four centimeters. They are distinctly encapsulated. The cells may be cuboidal or may become cylindrical, and are arranged in the form of single tubules; the glomeruli and different types of tubules are never reproduced. A papuliferous cystic adenoma, a small tumor with fibrous capsule in which the lining epithelium is elevated in a papillomatous manner, is occasionally seen. Adrenal. — Adenoma of adrenal, or struma lipomatosa suprarenalis of Virchow, generally develops from the cortex as an irregular nodular growth, yellowish or pale brown in color. It may remain small or may completely destroy the organ, sometimes attaining a very large size. The cells resemble those of the normal gland in structure, but are large, pale, and granular, as though filled with fine fat granules. Breast. — Many tumors of the breast combined with the formation of cysts have been described under the name of adenoma. In such cases the tumor is gen- erally a fibroma or a sarcoma, and has grown into the ducts of the gland as papillary projections. These are covered by the lining epithelium, which they push ahead of them in their growth, and which in- creases in consequence; but this is only secondary, and these tumors should be considered as connective- tissue formations. A diffuse enlargement of the breast due to uniform increase in the glandular elements has occasionally been described under the name of diffuse adenoma. This condition is bilateral, usually occurs about the time of puberty, and, strictly speaking, is a hyper- plasia and not a new growth. The true adeno?na is unilateral, definitely circum- scribed, and encapsulated. It usually occurs in young women, starting as small nodes in the upper or outer quadrant of the gland. It becomes round or oval in shape and sometimes grows to considerable size, though usually small. On section it is uniformly smooth, grayish-white, and quite firm, though occa- sionally it is soft and slightly nodular. Histologically, it may be composed of acini or of ducts lined by cylindrical epithelium. The stroma is fibrous and varies greatly in character and amount, but is looser and more cellular than that of the normal gland. According to the character of the inter- glandular tissue, it may be an adenofibroma, adeno- myxoma, adenosarcoma, etc. Adenocarcinoma is generally considered to be an unusual form of breast tumor. Halsted (1898), how- ever, reports five occurring in a series of 150 breast cancers. According to Halsted's observations, these growths differ from ordinary cancer of the breast in that they are softer, more pedunculated, and discharge a peculiar serous fluid when ulcerated. Histologically, they are composed of very large tubes lined by epithe- lium many layers deep. In three of Halsted's cases the growth was pure adenoma (malignant adenoma) ; in Fig. 43. — Fibroadenoma of the Mammary Glands. the others carcinomatous areas were present. Metas- tases in the axillary lymph nodes were found in none. Ovary. — The multilocular cystadenoma is the com- monest tumor of the ovary, and the one usually attaining the greatest size. It may be small or it may weigh a hundred pounds or more. It is a benign tumor and never produces metastases. The surface may have no epithelium, or it may have a single layer of flat epithelial cells. The numerous cysts of vary- ing size which make up the mass are lined on their inner surface by a single layer of cylindrical cells, 122 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adenoma often ciliated. The nuclei are oval and placed aeai the basement membrane. Some of the cells may be swollen and filled with clear contents, giving them the appearance of goblet cells. The contained fluid is thick, viscid, sometimes jelly-like, and may be color- less or, if there has been hemorrhage, yellowish or red- dish-brown. This fluid is formed by secretion from tli,. epithelial cells, by the transudation of serum from the blood-vessels, and by the degeneration of the epithelial cells. The most important chemical sub- Fig. 44. -Papillary Adenocystoma of the Ovary. X 10 diameters. stance in the fluid is pseudomucin, a true secretion of the newly formed epithelial cells. It does not occur in the normal ovary, in dropsical Graafian follicles, or in the parovarium. Calcification or necrosis of the cyst wall may occur as secondary changes. Both are unusual. The papuliferous adenocystoma is characterized by an ingrowth into the cyst of a papuliferous connective tissue covered with epithelium. On cross-section the appearance is that of gland tubules. The papillary growths may be prominent, or they may appear simply as fiat excrescences on the surface of the cysts. The epithelium is similar in character to that in the multilocular adenocystomata. This tumor is not malignant in the ordinary sense; but after rupture of the cysts a local growth on the neighboring perito- neum may occur. These growths are supposed to originate from the epithelium of mature or residual embryonic follicles or from the germinal epithelium of the ovary. Pfliiger has pointed out the glandular structure of the ovary, and Spiegelberg and Langhans have shown in the ovary, even after birth, residues of its embryonic glandular structure. Doran, as a result of his inves- tigations, believed that the tumor might originate in childhood or even in the intrauterine period. Williams states that the papillary adenocystomata originate from the epithelium on the surface of the ovary or from that of the Graafian follicles, or from both. Adenocarcinoma of the ovary may originate in the ovary, may develop in a papuliferous adenocystoma, or may be secondary to a similar growth in the uterus. Thyroid. — Aside from the hyperplastic changes associated with the condition known as goiter, circum- scribed adenomatous tumors of the thyroid occur. These appear as soft nodular growths composed of glandular tubules lined by tall cylindrical epithelium. Within these tubules papillary growths sometimes appear (adenoma papilliferum). Within the tubules is seen the colloid material characteristic of the normal thyroid. Although this tumor is one of the purest types of adenoma, it may produce metastases. It may also by direct extension invade the structure of the larynx. Testicle. — The form of tumor as it occurs in the testicle is generally known as cystadenoma. It may occur in the child or in the adult. It is attributed by some writers to error in development. Two forms are recognized. In one the tubules are lined by cylin- drical cells which sometimes have cilia, their contents being a clear or blood- tinged slimy fluid; in the other the epithelium is stratified and the contents a greasy substance with many fatty epithelial cells. The Fig. 45. — Papillary Adenocystoma of the Ovary; more strongly magnified than Fig. 44, in order to show the cyst wall, the papil- lary ingrowths of connective tissue, and the epithelium lining the papillary projections. As seen in cross section this epithelial structure gives the appearance of a glandular growth. growth usually starts in the testicle and may attain a large size. Instances of carcinomatous changes have been reported. Prostate. — The tumor usually occurs in this organ as an adenocarcinoma and is rare. It appears as soft, nodular masses which project into the urethra or neck of the bladder and invade surrounding tissues. Ulcera- tion is frequent, and when it occurs is accompanied by copious hemorrhage. Pituitary Body. — Adenomata of this structure are rare, but are occasionally reported in connection with cases of acromegaly. They may be as large as a 123 Adenoma REFERENCE HANDBOOK OF THE MEDICAL SCIENCES pigeon's or hen's egg; may protrude from the sella turcica, press on the brain, and extend even into the ventricles. Histologically, they are made up of large, tortuous, sometimes branching tubes lined by epithelial cells. Pancreas. — Adenomata of this gland are not com- mon. They are generally of the racemose type. Cesaris-Demel (1895) reports a distinctly encapsulated adenoma the size of a dove's egg in an atrophied pan- creas. The cells were irregular and primitive, occurring in one and sometimes in several layers, generally arranged in alveoli. Lacrymal Gland. — Adenomata of this gland are not very common. They generally occur in persons of advanced age. By pressure they may interfere seriously with the movements of the eye. They do not tend to become malignant and are only trouble- some on account of their size. Adenocarcinoma has been reported, but is very rare. Pineal Gland. — The occurrence of adenomata of this body is occasionally referred to in the literature. Richard Mills Pbarce. Adenoma of the Skin. — Adenomatous proliferation of the cutaneous glands is an extremely rare occur- rence, and it is only within a comparatively recent period that the condition has been recognized. Hypertrophy of the skin glands, on the other hand, is a concomitant of many chronic local disturbances of nutrition, and doubtless in some of the cases recorded as adenoma there has been confusion between this condition and hypertrophy. The considerations involved in the differentiation of hypertrophy and adenoma have been discussed in the preceding article. It must be noted, however, that all these growths are probably of congenital origin, and should be classed with the nrevi. The terms na?vus sebaceus and nsevus sudoriparus respectively are to be pre- ferred to the designation of adenoma. Adenomata of the skin naturally fall into two classes: adenoma of the sebaceous glands (adenoma sebaceum), and adenoma of the sudoriparous glands (adenoma sudoriparum). Adenoma Sebaceum. — Synonyms: Na?vus seba- ceus; Vegetation vasculaire (Rayer); Naevi vasculaires et papillaires (Vidal); Adenoma of the sebaceous glands; Steatadenonia; German, Talgdrusenadenom; French, Adenome s£bac6. The earliest recorded cases of the disease are found in the writings of Rayer and of Addison and Gull, who, however, failed to interpret correctly the anatomical condition, which Balzer was the first to recognize, though Balzer's case, curiously enough, has been shown by later investigators to be one of acanthoma adenoides cysticum. Cases have since been described by Hallopcau and Vidal in France, Mackenzie, Pringle, Jamieson, and Crocker in England, and Caspary and Boeck in Germany. The first case recorded in America was described by the present writer in 1S93, and many cases have been observed since that time The disease manifests itself in the form of small mul- tiple benign tumors, which may be distributed gener- ally on the face, but occur most frequently at the sides of the nose. Their distribution is usually fairly sym- metrical, but in Jamieson's and one of Crocker's cases they were limited to one side of the face, and in my own case the lesion was in the form of a linear patch on the forehead. The lesions in some cases were present at birth or appeared in infancy; but a more active growth, as to number and size of the tumors, has been noted at the time of puberty. In Caspary's case and in my own they did not appear until the seventeenth and the nineteenth year respectively. The individual growths seldom undergo any change after they have attained their development, though involution of a few of the nodules with resulting faint cicatrices has been noted. The little tumors vary in size from one to five milli- meters, are usually round and convex in shape, and the epidermis over them may be smooth or have a rough and somewhat warty appearance. Their color may be that of the normal skin, or they may have a brownish or even bright red hue. The color depends greatly on the presence or absence of telangiectases, which often appear as fine lines ramifying over their surface, and in some cases may form so striking a part of the tumor as to give the whole the appearance of a vascular nevus. In Vidal's case and in mine there was cystic degeneration of a part of the tumors, giving the appearance of small yellow nodules from which on incision a drop of inspissated sebaceous matter could be squeezed. Some importance has been at- tached to the fact that in many of the cases there were other striking abnormalities of the skin: warts, pigmented and hairy nevi, and small pendulous fibro- mata indicating a congenital tendency to malforma- tions of the skin. It is probably only a coincidence that many of the cases have occurred in persons of deficient intelligence, some of them epileptics. Anatomy. — Under the microscope the entire tumor is seen to be composed of larger and smaller masses, which bear the closest resemblance to the acini of nor- mal sebaceous glands. It is indeed only in the great number, extent, and complex arrangement of the lob- ules that an abnormal condition becomes apparent. In some cases solid epithelial buds are given off from existing sebaceous gland acini, and the cells of these buds later undergo the peculiar fatty changes indica- tive of the glands from which they take their origin. Unna, who draws a very sharp distinction between hypertrophy and adenoma of the sebaceous glands, re- gards most of the published cases as examples of hypertrophy. The treatment of the condition is indicated only for cosmetic purposes. When the lesions are few in number they may be removed by excision, by scarification, or by electrolysis. When they are very numerous, any form of operative interference is inadvisable. Adenoma Sudoriparum. — Synonyms: Naevus su- doriparus; Adenoma of the sweat glands; Spirade- noma; Syringadenoma; German, Schweissdrusen- adenom; French, Adenome sudoripare. The disease which has been described under the various names of hydradenomes eruptifs, syringo- cystadenoma, epithelioma or acanthoma adenoides cysticum, etc., and which was formerly regarded as an adenoma of the sweat glands, is now known to have no connection with these structures. The reader is referred to the article on Epithelioma of the Skin for an account of this condition. In view of the fact that the sweat gland is an ap- proximately uniform cylindrical tube, the distinction between hypertrophy and adenoma of these glanda can readily be made. Any deviation from the typical structure in the form of lateral budding or outgrowth suffices to constitute adenoma, provided, of course, that the new formation does not break through the membrana propria of the gland. From this point of view adenoma of the sweat glands is by no means a rare occurrence. It is frequently found in connection with other diseases of the skin, especially in associa- tion with tumors and malformations of the blood- vessels of the cutis and hypoderm, and with cancers of the skin. Under these circumstances, however, the adenoma constitutes merely an interesting micro- scopical condition without giving rise to any clinical symptoms. In these cases the adenomatous forma- tion affects only the coiled portion of the gland, and it is a noteworthy fact that in all the observations hitherto recorded there has been a sharp distinction between adenoma of the coil and adenoma of the duct. This distinction has given rise to the terms spirade- 124 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adladorlioklnrsla noma and syringadenoma. Adenomata of the sweat glands occurring independently are of extremely rare occurrence. (Jnna in his " Histopathology " was able to cull only ises of spiradenoma from the literature, to which he added a seventh. The tumors varied in size in the different cases from a small chestnut to a hen's egg; were found on the head, neck, or extremities in mid- dle-aged .11 elderly people lone case in a child); and presented no characteristic clinical features. The diagnosis ran be made only with the microscope. The proliferation occurs in the form of solid epithelial buils. which usually show a tendency to grow in curved lines as they increase in length, and to become canal led like the structures from which they took their origin. Of the syringadenomata there is but a single un- doubted ease on record, that of Petersen. It was in the form of a papillary ncevus unius lateris on the neck, trunk, and thigh of a girl of twenty. The adenomat- ous proliferation was confined strictly to the ducts of the glands, which appeared considerably widened shortly above the coil, the cubical epithelium became cylindrical, and outgrowths developed which were sometimes solid and sometimes canalled. These out- grow tin divided repeatedly like the branches of a tree, and produced thus the semispherical or mushroom form of the tumors. The new-formed tubes were lined with a distinct membrane and showed no signs of colloid degeneration. Sigmund Pollitzer. Adeps. — Lard. "The prepared internal fat of the abdomen of the hog (Sms scrofa, var. domestica Gray), purified by washing with water, melting and strain- ing" (U. S. P.). The tissue from which lard is obtained, lying at each side of the backbone and enclosing the kidneys, and which goes by the name of " leaf lard," is washed, chopped, cleaned from connective bands and tra- becule, and then, with a little water, exposed to a boiling temperature until the connective tissue is softened and the fat has run out; it is then strained, and the heat continued until the water is nearly removed and the melted fat is clear and homogeneous, when it is poured out and cooled. If a very fine product is desired, it should be filtered in a hot filter- ing apparatus. Lard should be of a soft solid consistency, white, unctuous, with a faint but not at all rancid odor, and a bland taste. Its specific gravity is about 0.917 at 25° C. (77° F.) and it melts at 3S° to 40° C. (100.4° to 104° F.). It is insoluble in water and very little soluble in alcohol. Olein, palmitin, and stearin are the principal con- stituents of lard, their relative proportions (upon which its consistency depends) varying considerably. Commercial lard is so apt to be impure, either being mixed with water or salt, or having a portion of its liquid oil removed, that it is in general unfit for medicinal use, and the apothecary will do well always to prepare his own. Ordinary lard rather rapidly becomes rancid and irritating, but if perfectly pure and free from water it will keep, in a cool place, for a very long time. When it is to be used during warm weather, five per cent, of it, or more if necessary, should be replaced with white wax. For pharmaceutical purposes it is scented, as well as preserved, with benzoin, a little of the balsam being tied in a bag and suspended in the melted lard for two hours. Thus treated, it is almost entirely permanent, besides having an agreeable odor. Lard is an article of food, and is emulsified, like other fats, when taken into the intestines, without any particular physiological action. As an external dressing, it is protective and bland in a high degree, qualities which have given it its popularity as a basis of ointments and cerates. Those of the L'nited States Pharmacopoeia follow: A. benzoinatus, just mentioned. ( era) uin, Ceratum cantharidis, Ceratum extract! cantharidis, ('. resins, Unguentum, I'ng. bydrargyri, l"ng. mezerei, Ung. iodi, etc II H. Rusby. Adeps Lanjc Hydrosus. — Lanolin. Hydrous Wool- fat. "The purified fat of the wool of sheep arks Linne) mixed with not more than thirty per cent, of water" I I'. S. P.). Freed from water, this sub- stance is the Adeps I. awe or WooL-fai of the Phar- macopoeia, but it is chiefly used fn its hydrous form. Under the title of lanolin. Oscar Liebreich propo ed, to serve as a basis for ointments, the peculiar body that results from the mixture of a cholesterin fat with water. The cholesterin fats are peculiar, in com- parison with ordinary glycerin fats, in not decompos- ing, in •' taking up" and holding in intimate blending an equal quantity of water, in mixing also with gly- cerin, and in possessing a high diffusion power. By reason of the latter power, lanolin used as an inunction ointment is supposed rapidly to impress the system with any absorbable active drug substance that may be incorporated with it. This wool-fat, or lanolin, as it is still commonly called, is a yellowish-white material of ointment-like quality and a faint char- acteristic odor. It is insoluble in water, but yet will mix with twice its weight of water and still retain its unctuous quality. It melts at about 40° C. (104° F.), separating into an upper oily and a lower aqueous layer. It is somewhat sticky, but this quality can be removed by the addition of from twenty to twenty-five per cent, of some ordinary oil, such as castor oil, cr of vaseline. Clinical experience with lanolin does not seem fully to realize the expectation of unusual power on the part of the substance to penetrate the skin, on inunction. Nevertheless, lanolin makes a very serviceable material for inunction purposes, either by itself or medicated. H. H. Rusby. Adiadochokinesia. — This term (also within adiado- chokinesia) was proposed bj* Babinski of Paris, to designate a peculiar difficulty observed in certain patients suffering from cerebellar disorder. It consists in an inability to perform rapid alternating move- ments, such as opening and closing the hands; rapid supination and pronation; finger play, such as piano playing; extension and flexion of the forearm on the arm. It has been found, further, that the symptom ha- a slightly wider significance than that originally attributed to it, and "is of considerable diagnostic importance. The defect, in order to be called adia- dochokinesia, should not be complicated by the pres- ence of any loss of muscular power, or of disturbance of sensibility. It is well recognized that clumsiness in performing rapid alternating movements exists in ordinary hemiplegia, in a number of ataxic states, due to impaired sensibility, but the significant feature of adiadochokinesia is that it should be found without the presence of muscle palsies or of sensi- bility disturbances. It is one of a series of closely related motor disturbances due to interference in certain of the cerebellar paths, and one which, taken in conjunction with other disturbances of cerebellar mechanism, is extremely useful in the differentiation of cerebellar disorders. Essentially, according to Babinski, it consists of a lack of proportion, a lack of timing, as it were, between the successive move- ments. In other words, on the affected side there is a time loss, or a delay in the motor impulse. This time loss, which produces the disproportion between the series of movements on the sound and on the affected side, is largely due to the disturbance in the automatic tonic mechanism, the most important paths for the maintenance of which lie in the cerebel- 125 Adiadochokinesia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES lum, I lie superior cerebellar peduncles, and the red nucleus. When this symptom is present in its pure form, a lesion of the cerebellum, or of the superior cerebellar peduncle almost invariably has been found, yet, at the same time, a few cases have been recorded in which the lesion has been extra-cerebellar, but not non-cerebellar, by which is meant that although the cerebellum itself has proved to be involved, yet nevertheless cerebellar tracts have always been implicated. Thus, a few patients showing this symptom have been known to have frontal tumor. Here the cerebcllo-thalamoeortical paths have been implicated. Clinically, the majority of the patients have shown tumors of the cerebellum. Some mid- brain tumors, or midbrain hemorrhages with impli- cation of the superior cerebellar peduncles have also shown this symptom. Smith Ely Jelliffe. Adipocere. — (French, adipocere, gras des cadai'res; German, Fettwachs.) As the name suggests, adipo- cere, from Latin adeps, lard, and ecru, wax, is a material resembling in its gross appearances fat and wax. It is a semitranslucent, white, or slightly yellowish substance of about the consistency of cheese at ordinary temperatures; has a greasy feel, and yields slightly when pressed between the fingers. If a piece be rolled between the fingers for a few minutes it becomes much softer. When rubbed with water it forms a lather. Its composition is that of a soap, being made up of the calcium soaps of palmitic and stearic acids and also of acid ammonium soaps. Examined under the microscope it shows, occasion- ally, very numerous scales having a crystalline form; more commonly nothing but fat globules is to be seen. If it be melted and again allowed to cool, it is found, often, to have crystallized in round masses made up of needle-shaped crystals, radially arranged; hence like stearin. Most of the specimens of adipocere with which one is familiar come from the macerating troughs of anatomical departments and from museum jars which have long contained specimens immersed in dilute alcohol. It thus represents the results of a metamorphosis of dead animal tissues placed under peculiar circumstances. The only special point of interest in connection with adipocere lies in the fact that it is occasionally found in dead bodies which have been buried a con- siderable time. In fact, nearly all the structures of the body, except the bones, have been found con- verted into this material. For centuries its presence had been noted in disinterred corpses, but no oppor- tunity was afforded for studying it on a large scale until 1876, when, upon the removal of the bodies from one of the cemeteries in Paris, a considerable proportion of those buried in the common grave were found by Foucroy to have been converted, to a greater or less degree, into this peculiar, fatty, wax- like material, and to it he gave the name by which it has since been known. The conditions favoring its formation in buried corpses are still unknown. Doubtless moisture is always necessary; but why, of six or eight bodies buried in close proximity, and hence presumably under like conditions of soil and moisture, one should undergo almost complete change into adipocere, while the others undergo ordinary putrefaction, as has been observed, is at present inexplicable. At one time it was thought that adipocere might be of medicolegal importance in helping to determine the length of time a corpse had been buried. Foucroy be- lieved that thirty years was required for its formation. Later, this was reduced to one year; and Caspar mentions finding adipocere in the body of a new-born child which had lain for three months in a house cesspool. It is therefore impossible to establish an idea, from the presence of adipocere in a corpse, as to the length of time it has been buried. Artificially, adipocere can readily be produced, either by soaking muscle in dilute nitric acid for two or three days and then washing it thoroughly in warm water, or by allowing the muscle to soak for months in a trough supplied with running water. Adipocere is probably closely allied to cholesterin. W. W. Gannett. Adiposis Dolorosa. — At a meeting of the American Neurological Association, held in New York in June, 1892, the writer presented the histories and photo- graphs of three cases of an affection which up to that time had not been recognized. Four years previously the writer had described the symptoms which con- stitute this affection in reporting a case under the title of a subcutaneous connective-tissue dystrophy. Subsequently he grouped this case, a second described by Dr. F. P. Henry and a third rase discovered in the wards of the Philadelphia Hospital under the name of adiposis dolorosa by which the affection has since been generally known. The two principal features, fat and pain, are implied by the name. German writers in reporting cases of this disease use the terra "adipositas which is etymologically correct, while the word adiposis is of mixed origin, being made up of a Latin root and a Greek termination. It has, however, been used for generations, more especially by English medical writers and is paralleled by other mongrel words, long approved by custom, such as ' tierminology." Again "adipositas" is itself a 'coned word; it is not found in any Latin writing, the real Latin word being "obesitas," which if we insist upon being correct, we should use. Subsequent to the descriptions published by the writer, cases were reported by Collins, Peterson, Ewald, Eshner, Spiller, F6re and others and in 1901, Louis Vitaut 1 published a thesis upon the subject. His description was full and accurate, so much so indeed that subsequent observation necessitates but little modification of it. Up to the present time a large number of cases, possibly a hundred, have been placed on record. Among the more important recent publications were those by Frankenheimer, 2 Price, 3 and Poirier. 4 The three cases which the writer grouped together in his original paper are presented in brief abstract herewith: Case I. — M. G., age fifty-one, female, native of Ireland, domestic, widow. Family and early history without significance. In November, 1886, she was admitted to the surgical wards of the Philadelphia Hospital for the rupture of a varicose vein of the leg. In the following February she was transferred to the medical wards for a severe attack of bronchitis. Later she had an attack of severe pain and swelling in the right knee, attended by chill and fever. She was treated for rheumatism and obtained prompt relief. Two weeks after this she complained of a sharp darting pain in the right arm. It began on the outer aspect above the elbow and gradually increased in severity and extent, spreading upward to the shoulder and neck, and downward to the forearm and hand. It was shooting and burning in character. She felt at times as though hot water were being poured upon the arm, and again as though the hands and fingers were being torn apart. No rise in tem- perature was noted. The pain was often paroxysmal, but it was never absent. On June 4, 18S7, she was transferred to the nervous wards of the hospital and came under the care of the writer. Her appearance at this time was striking. She was a tall, large-framed woman who looked as though she had at one time presented a fine physical develop- ment, but she seemed unnaturally broad across the back and shoulders. On removing the clothing, an 126 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Adiposis Dolorosa enormous enlargement of these parts was disclosed. The enlargement affected both shoulders, the arms, the back and the sides of the chest. It was most marked in the upper arms and bark, forming here huge and somewhat pendulous masses. It was ■ neSS about the knees, followed by .--welling, which gradually increased. At first she thought that the swelling was due to her growing fat, but later she was astoni hed to sec that then- was a localized mass on the inner aspect of each knee. At the time there was dull aching pain in the affected p _^ aBK ^pa Later, the right arm became involved, a mass making its appearance on the outer aspect. Her body, as she then observed, had also become larger, as her stays wen- too small for her. During this time, while -till in California, inability to perspire freely, except at the Turkish bath, was marked, and was part of her reason for ^H| coming East. Since she has been in I'liila- I delphia the lack of perspiration has not bi en as marked as before. Various plans of treatment were tried, but did not influ- ence the progress of the disease, i.e. the growth of the swelling. Five or six years ago, injections of chloroform were made into the swellings on the inner sides of the knees, but no good was accomplished. Painful ulcerations were the result, and scars of considerable size mark their loca- tion. Jrat onbaek: elastic and yet comparatively firm to the touch, and it was impossible to produce pitting. In some situations it felt as though finely lobulated and in others, especially on the insides of the arms, as though the flesh were filled with bundles of worms. The skin was not thickened; it did not take part in the swelling, and it was not adherent to the subjacent tissues. In addition the swelling was very painful to pressure. Pronounced pressure appeared to be absolutely unbearable. The nerve trunks also were exquisitely sensitive, but this painful condition was not by any means limited to them, but permeated the swollen tissue as a whole. ad Upper Arm. About five years ago a slight swelling appeared in the epigastrium. This gradu- ally increased in size until it resembled the breasts in shape, and afterward spread so as to involve nearly the whole abdomen. From the knees the process extended to the thighs, and gave rise to large masses on their outer side and about the hips. At various times she had suffered with pains apparently situated in the enlarged tissues, or running down the limbs. Sometimes these attacks were fairly well localized in one limb, in one side, or about a joint. Case III. — M. M., age sixty, widow, a tailoress by occupation, and a native of Germany. Family and early personal history likewise without significance. On examination the patient was found to be excessively Fig. 47. — Another View of Author's First Case. Case II. — E. W., female, age sixty-four, married, native of England. Family and early personal history without significance. Present malady began about fifteen years ago, when she was forty-nine years old. At that time she was living in California. The first thing noticed was a constant feeling of cold- feeble. For some two weeks she had been unable to walk. She lay, for the most part, in a quiet, apathetic state, though when aroused, she answered questions slowly, but intelligently. She was also somewhat deaf. Examination further revealed soft, fat-like masses 127 Adiposis Dolorosa REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 48. — Author's Second Case. or swellings in various situations. Thus, a large, soft mass was found over either biceps, and others, some- what smaller, over the outer and posterior aspect of either upper arm. Two large masses were found over the belly, separated above the umbilicus by a deep, transverse crease. Another gave excessive prominence to the mons Veneris. From the back of the neck, at. its lower part, sprang a big mass like a hump, while a diffuse swelling gave a cushion-like coating to either half of the back, and extensive deposits gave unnatural prominence to either hip. In marked contrast, the deposit was absent from the forearms and hands, from the face, from the thighs and legs, and from the buttocks. The glu- teal regions, in fact, seemed flattened and sloping. The deposit over the bark seemed tolerably firm and resistant; over other portions it was quite soft, though elastic, and exhibited the same nodular feel noted in the previous cases. Further, it was discovered at once that these masses were painful to the touch, the patient complaining very much when only moder- ate pressure was exer- cised] This was espe- cially true of the deposits over the arms and back of the neck. In addition the patient complained of stabbing pains in the deposits, more marked in the regions just men- tioned. There was no tenderness over the nerve trunks. She complained also of headache. These cases presented in brief fatty deposits, ac- companied by pains, shooting, burning, or stabbing in character. Sometimes the pain occurred in paroxysms and at such times there was present an increase or induration of the swellings. Sometimes new deposits were formed during such crisrs. Since these cases were published, enough has been learned about the affection to enable the following systematic description of the disease to be presented. Etiology. — In a proportion of the cases, neuro- pathic elements are noted in the heredity; occa- sionally also in collateral relatives. Again, it is now and then noted that other members of the family are obese as was noted by Eshner, in one of whose cases the mother of the patient was very stout and in another of the writer's cases in which the father was excessively stout. Occasionally it has hap- pened that several instances of adiposis dolorosa were noted in members of the same family. Chee- vers has placed on record the case of a man whose father and sister had the same disease as the patient; Hammond reports two cases occurring among sisters. The affection appears to predomi- nate especially in the female sex, the proportion being about six to one. It is difficult to make definite statements as to the age at which the disease appears. The young- est case reported is that of Hale White in which the disease began at twelve years of age, while the oldest patient thus far recorded was seventy-eight years of age. According to Frankenheimer, the majority of cases in men occur between thirty and forty years of age and in women between thirty and fifty years of age. Now and then there is an an- tecedent history of alcoholism or of syphilis. The significance of these facts, however, is open to ques- tion, but as has been pointed out by Price and has been emphasized by Lorand, both alcoholism and syphilis not infrequently cause degenerative changes in the ductless glands, structures which are probably at fault in the production of adiposis dolorosa. In a case described by E. W. Taylor, the disease developed while the patient was convalescing from an acute alcoholic neuritis. In quite a number of cases ex. cessive menstrual flow and even uterine hemorrhages ■ EHk'^ Is m ~ \ / 1 x / --*fWj, Fig. 49. — Rear View of Author's Second Case. 128 REFERENCE HANDBOOK OF THE MEDICAL SCIENI I S Adiposis Dolorosa have been aoted. In one ease, that of Spiller; the adiposis dolorosa followed pregnancy, while in another, thai of Schlesinger, it followed an abortion. Quite :i number of cases finally have developed after the menopause. Fig. 50. — Author's Third Case. Among other facts, trauma has been noted in the ory; attention has been called to this especially by Guidiceandrea. In one case of the writer and in One of Eshner, trauma appeared to play a role of exciting cause. Emotional shock has also preceded the onset as in the case of Achard and Laubry. In Vitaut's case there appeared to be a mild infection of the digestive tract; in other cases exposure to cold and dampness, rheumatism, appeared to play a role. sionally also some other neurosis exists side by side with the affection, as in the woman reported by Henry and in a man reported by the writer, both of whom suffered from epilepsy. In othercases again, undoubted men- tal disease has been noted, and even com- mitment to an asylum for the insane has been resorted to in such cases. Symptomatology . — The symptoms as a rule appear very gradu- ally. Most frequently, as stated above, the patient is a woman. Up to the period of the onset of her symptoms, she has been apparently well and perhaps en- gaged with the usual household duties or other occupation. She has occasion at one time to notice a slight pain or tenderness in some portion of her body. These early symptoms of pain are very variable in character and in intensity. Most often it is a sensation of smarting or stinging more or less annoying because of its persistence. Sometimes the pain, even in the beginning is severe, though this is unusual. At other times the onset of symptoms is preceded by a sensation of cold in re- gions in which pain subsequently makes its appear- ance. As a rule the pains at first are not very pro- nounced and the patient is for some time able to Vol. I.— 9 follow her ordinary occupation. Furthermore, the pains arc not pei i tenl bul recur al intervals, the patient being comfortable for hour i and ometimes for days al a tunc. Little by little the pain become mure pronounced; they increase in intensity and t hen also accompa nied bj di tinol local changes. The pa- tient nal urally examine: I lie pari which is painful and may note these changes herself. Sometimes there is a little flushing of the skin and sooner or later a swelling is noted. At first it is hardly apprecia- ble but gradually becomes mi. re pronounced. The swell- ing may give a sensation to the linger of a, rather firm localized edema. As a rule it is in the beginning a small nodule — smaller than a wal- nut, rarely larger. Some- times a number of such swell- ings are noted at the same time. The affection contin- ues to evolve, usually slowly; the pains become more in- tense and more frequent and gradually the tumefactions change their character and finally become veritable tumors or great tumor masses. In rare cases the fatty deposit appears to make its appearance without either previous or con- comitant pain, the pain making its appearance only after the enlargements or swellings have for some time existed. This, as already stated, is unusual, the most common history by far being that just outlined. The pain is quite commonly paroxysmal, though in long established cases it may be continuous. In the intervals the tumefactions are usually tender or pain- ful to pressure. Vitaut recognized four cardinal symptoms, namely, Fig. 51. — Rear View of Author's Third <';tsr. swelling, pain or tenderness, asthenia, and psychic symptoms. The swellings may present themselves under three different aspects. Sometimes they are small, of variable dimensions, distinct from one another and readily isolated. Under these circum- stances they present what Vitaut has termed the nodular form of the disease. Sometimes they form extensive masses invading an entire limb or the seg- ment of a limb. To this condition Vitaut has given the name of the localized diffuse form. Finally a 129 Adiposis Dolorosa REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tumor properly speaking may not be present, but the entire body may be augmented in volume in conse- quence of a hyperplasia of the fatty subcutaneous connective tissue. This condition Vitaut has called the generalized diffuse form. When the affection presents itself in the nodular form, we notice at first pains variable in character, for example, stinging, itching, smarting, shooting, which is soon followed by a slight redness of the skin and a slight induration scarcely appreciable by the finger. If we examine the painful area, we feel a tumefaction usually of small size, at first yielding and later a little more resistant. The sensation is that of a firm edema which is not well differentiated from the surrounding tissue. The tumefaction appears to develop slowly in keeping with successive attacks or crises of pain. Gradually it becomes somewhat better defined, its volume increases and its consistence changes so that it no longer has the appearance of a simple tumefaction, but that of an actual tumor. Each increase of swelling is pre- ceded or attended by characteristic pains. The latter are sometimes so sudden in their onset and so severe as to cause the patient to cry out. During the height of the paroxysm, the tumor may resemble very closely, in the sensation which it gives to the fingers, a "caking breast." The painful crisis having passed, it is found that the dimensions of the swelling have distinctly increased. It has become perma- nently larger as well as more resistant and better defined. After repeated paroxysms, the swelling resembles a distinct tumor more and more closely. In certain portions the mass may appear finely lobulated, while in other parts it gives to the fingers the sensation of a bag of worms beneath the skin. Each painful crisis leaves behind it very appreciable changes. In an area where nothing existed pre- viously, we find after a crisis a diffuse edematous tumefaction; if the tumefaction has existed previous to the crisis, we find it transformed into a lobulated tumor more or less well encapsulated. Sometimes after a crisis we discover around the tumor a well- defined edematous zone which in subsequent crises undergoes a transformation such as the original mass itself had undergone. In this way the mass may eventually attain great size. The various stages of the evolution of these masses can be followed very closely by palpation. One and the same patient, besides, usually presents in various regions tumors in various stages of development. Painful crises supervene usually without appreciable cause; at times they are provoked by trauma and at others they ensue upon unusual exertion. The patient is frequently very positive in stating that slight con- tusions of the surface or that excessive fatigue provokes the painful crises. The swellings vary considerably in size. Some of the very smallest may be no larger than a pea, though so small a mass is the exception. More frequently the mass is of the size of a walnut or a small orange. .Much larger sizes are met with. The larger masses are, of course, evident to ordinary visual inspection, the smallest ones require to be sought for by palpation. If we examine the patient atten- tively in a good light, we are struck by the changes in the skin in certain areas. In places indeed it presents a bluish tint due to a slight superficial veining and if we examine such a region by the feel, we frequently discover a small subjacent tumor. Small as the tumor may be, it may betray its existence by this bluish tint in the skin which covers it. It happens sometimes that these small tumors become confluent and finally form a single large mass. Such a mass gives rise to a sensation like that of a varicocele or of a bag of worms. This sensation of a bag of worms is noted with especial frequency in the fatty masses which are loose and pendent. Swellings may occur in almost any situation except in the face, hands and feet. These are rarely, if ever, involved. Sometimes the swellings are symmetrical, especially in the beginning of the disease, but soon they group themselves about without any apparent order. They develop by preference over the limbs or in the segments of a limb. In some patients they are limited to the arms and thighs, or forearms and legs in others. Sometimes we find them on the thorax, abdomen, and lumbosacral region. In the stage of edematous swelling, the tumor masses pass without exact limitation into the surrounding tissue. As a rule the skin is but slightly movable over them. Later, however, distinct tumor masses, more or less encapsulated, are formed. They are mobile in all directions. They are slightly adherent to the skin so that if one tries to displace the overlying skin, motion is transmitted to the swelling. At times, however, the skin can be gathered in a fold above the tumor. These masses again, it must be borne in mind, are painful not only during the crises, but are tender to pressure; this tenderness as already stated, may persist in the intervals between the paroxysms. When the painful swellings are localized, though diffuse, they may begin primarily as diffuse wide- spread enlargements or a number of nodules may become confluent and in this way present a diffuse mass. However, the more frequent manner is the gradual appearance of a diffuse mass without the previous formation of nodules. In such a case the pains are felt over a correspondingly extensive region. At first the entire region presents an edematous swelling easily observable by the eye. Subsequently the evolution of the mass is substantially the same as in the nodular form. Painful crises are here again present and the swelling increases in size with each successive attack. Finally a mass is formed which is resistant and painful to pressure. It may be quite smooth or it may be finely lobulated, or separate; apparently encapsulated tumors may be found im- bedded in the general lipomatous mass. It is difficult to make out the limitations of the latter as clearly as in the nodular form. These diffuse masses are found more frequently upon the thighs, the buttocks, the back, the abdomen, and the upper arms. The swell- ings are usually very painful and during a "crisis" may be much nodulated and may present the sensation to the fingers of a breast distended by milk, i.e. a sensation of a caked breast. When the affection presents itself in the generalized form, the appearance may be less distinctive but the origin and course are the same. The swelling may appear rapidly, even suddenly and involve the greater part of the surface of the body and limbs, exclusive of the face, hands, and feet. It steadily increases and results in a general lipomatosis. Most commonly, however, like the localized diffuse form, it begins in a certain part, for instance the abdomen, sometimes upon one side and then begins to diffuse itself gradu- ally over the neighboring portions of the trunk and limbs. In other portions of the body similar swell- ings may make their appearance, perhaps at the same time, perhaps a little later and these becoming confluent with the original mass and with each other, a diffuse lipomatosis again results. The parts affected are ordinarily the thighs, hips, buttocks, abdomen, chest, upper arms, and forearms. In exceedingly advanced cases, small masses of fatty tissues may be observed over the thenar and hypo- thenar eminences and even on the soles of the feet; in one case the writer observed even a slight invasion of the face. Even in excessively diffuse forms, with enormous increase of the body weight, the writer has never observed an invasion of the backs of the hands or the dorsum of the feet. The swelling of the generalized diffuse form is much less resistant than the nodular or localized diffuse forms. The entire fatty mass is spontaneously painful and tender to pressure, though the pain is not 130 KKIT.K i:\CK HANDBOOK OF THE MEDICAL SCIENCES Adiposis Dolorosa equally diffused but more pronounced al certain times and in certain areas than others. Local II net na- tions of induration also are noted. Sometimes the Buffering, owing to the universal pain and tendernes is exceedingly great; it may be so pri inced as to prevent any motion on the part of the patient and to immobilize him in bed. The nodular form is the most common. A word remains to be said regarding the character of the pain. This occurs either spontaneously or is readily elicited by pressure. Most frequently the pain precedes the appearance of the edematous swellings. Sometimes it comes on at the same time as the swelling; more rarely it is not noted until after the swelling has made its appearance. Slightly marked and intermittent at first, the pain becomes more violent after the disease has been established. It is described by the patient as stinging, burning, pinching, darting, or even lancinating. Most frequently it darts and radiates or is diffused in and about the nodules. It does not follow the large nerve trunks or indeed any nerves. The patient describes the pain as though it was situated in the thickness of the masses. One characteristic is presented by all cases, namely the paroxysmal exacerbations of pain already described. Suddenly and without cause or following an effort or trauma the patient again feels active pain. At the same time the new formations increase in volume. In addition to the fatty masses and the pain there an 1 present the asthenia and the psychic symptoms. All or almost all of the patients present the symptoms of a general asthenia. The patient is very readily exhausted. Even in cases in which the muscular development is good this fact is early noted and in cases which are advanced, the asthenia is very pro- nounced. Indeed the patient may become bedridden by reason of this weakness as well as because of the pain which is usually made worse by exertion, espe- cially in advanced cases. Psychic symptoms are also very frequently present. A cerebral asthenia or cerebral exhaustion is rarely absent. There is present in addition usually great irritability. This is at times so marked as to be at- tended by a change in character and in disposition. The patient frequently quarrels with his neighbors in the wards and to such an extent that isolation may become imperative. Sometimes the patient thinks that the other patients or the nurses " are against her." Systematized persecutory ideas are, however, not present. The sleep may be broken and there may be distressing dreams and nightmares. One of Eshner's patients had to be committed to an asylum because of the pronounced character of the mental disturbance. Hale White's patient had two attacks of mental disturbance and Guidiceandrea has noted delusions of persecution and a true dementia. Other symptoms are also occasionally noted. Thus there may be present lessened sensibility, to touch, pain, and temperature or paresthesias may be complained of, such as velvety sensations in the finger tips and in the soles of the feet. Patients have also complained of sudden sensations of cold or of heat, of formication, or of cramps in various parts of the body. Symptoms may also be presented by the special senses. Thus narrowing of the visual fields has been noted. In others, subjective sensations, such as phosphenes and muscae volitantes. In one case amaurosis was observed; this disappeared under thyroid treatment. In a case of the writer there was noted a circinate retinitis — a mass of partly fibrinous and hemorrhagic exudate in the center of the retina, surrounded by crescents of fatty degeneration in Mueller's fibers. The auditory perception has been observed to be diminished in a number of cases. Occasionally tin- nitus aurium has been recorded and finally in one of the writer's cases, smell and taste were distinctly impaired. Vasomotor phenomena are quite often present. The skin over a nodule may present no changes what- ever. On the oilier hand, it may be no ed that it is somewhat injected during a crisis of pain or much veined and slightly bluish. Sometimes the face is much flushed, especially over the malar regions and the forehead or it may be tin- nnk. \o induration or swelling accompanies these changes in color. Cya- nosis of the extremity and transitory edema have also been observed. A very common symptom noticed is that the flesh bruises very readily and quite commonly small ecchymoses on various portions of the limb and trunk are revealed at the time that the patient is examined. These ecchymoses or subcu- taneous bleedings make their appearance sponta- neously and independently of trauma. In keeping with this fact are probably the metrorrhagia, excessive menstruation, epistaxis, hematemesis variously ob- served. Trophic changes in the form of ulcerations, blebs, and bulla have been noted. It is important to add that, there is quite commonly a marked dryness of the skin. In women there is frequently present a history of relatively early cessation of the men- strual function. Among unusual complications, noted in adiposis dolorosa are changes in the joints. Cases showing such changes have been noted by Renon and Heitz and by the writer. It appears that the changes are in part due to the fatty infiltration and that this fat is painful to pressure. In other cases it is probable that an actual synovitis is present and in one of the writer's cases, distinct changes were revealed in the cartilage and bones by the z-ray. Price has also noted changes in the joints confirming these findings. Price together with Hudson also noted changes in the bones — in the dorsal vertebrae and in the ribs — the changes being evidently trophic in character. Their existence was confirmed by the skiagraph. Price and Hudson called attention to the possible signif- icance of these findings in view of the frequency of pituitary changes in adiposis dolorosa. The course of adiposis dolorosa is essentially chronic. The progress is slow, the patient being better or worse by turns according to the occurrence of paroxysms of pain. In well-established cases, the suffering is con- tinuous, subject always to more or less marked exacerbations. In the majority of cases the patient becomes exceedingly obese, the weight often running from two hundred to three hundred pounds. In the nodular form, the weight may undergo very slight if any increase. The tendon reflexes may be normal or increased. Most frequently they are diminished and sometimes absent. Occasionally the skin reflexes are lost. Coincident gross nervous or other disease has, as may be expected, been noted a number of times. Thus hemiplegia and aphasia coexisted in one case; in another sclerosis of the columns of Goll and in another still involvement of the lateral tracts. Pathology. — Up to the time of writing, eight autop- sies have been held. These indicate that in adiposis dolorosa there is some disturbance of the internal secretions, excessive formation of fatty tissue and an interstitial neuritis of the nerve fibers contained in the deposits. Price has summarized the results of the various autopsies as follows: Cases I and II. — Dercum: Macroscopic disease of the thyroid, the glands being enlarged and the seat of calcareous infiltration. Case III. — Dercum: Irregular atrophy of the thyroid, extensive interstitial neuritis of peripheral nerves in fatty deposits, degeneration in the columns of Goll. Case IV. — Burr: Glioma of the pituitary body; colloid degeneration with atrophy and absence of secreting cells in many acini of the thyroid gland; 131 Adiposis Dolorosa REFERENCE HANDBOOK OF THE MEDICAL SCIENCES interstitial neuritis of terminal filaments; sclerotic ovaries. Case V. — Dercum and McCarthy: Adenocarcinoma of pituitary body, thyroid normal, right suprarenal gland hypertrophied, hemolymph glands, interstitial neuritis, undeveloped testicles. Case VI. — Guillain and Alquier: Hypophysis doubled in size with marked increase of connective tissue in the glandular portion and changes suggesting an alveolar carcinoma; thyroid hypertrophied with increase in connective-tissue stroma. Case VII. — Price: Inflammatory changes in thyroid, with marked increase in the interstitial connective tissue, one whole lobe being especially infiltrated, the other showing compensatory hypertrophy. In- flammatory changes in hypophysis, with presence of a condition suggesting alveolar or glandular carcinoma, interstitial and parenchymatous neuritis, sclerotic ovaries. Case VIII. — Price: Marked increase in the con- nective tissue of the thyroid gland, dilatation of the acini, with infoldings of the cuboidal epithelial lining. The same changes in the hypophysis as were found in Cases VI and VII, but less marked. No abnor- malities of the adipose tissue. Delecq thinks that disease of the thyroid, testicle, ovary, and pituitary body may be causes of adiposis dolorosa. Von Schroeter concludes that adiposis dolorosa is due to a dysthyroidismus. Pineles regards the disease as a result of the disturbance of function in numerous blood glands and that there are present hypothyroidism, genital atrophy, and changes in the hypophysis. The thyroid gland, it will be noted, showed unmis- takable changes in seven of the eight autopsies. These changes are very interesting and are well illustrated by the findings in the third autopsy of the writer in which the gland was submitted to microscopic examination. The changes observed were indicative in part of the hypertrophy and in part of atrophy. In certain portions of the gland, numerous small acini appeared to be in process of development. Exceedingly large acini distended by deeply staining colloid material were also present, while plications and papillary outgrowths of the walls of he acini seemed to be an attempt to increase the secreting surface. Other portions of the gland were distinctly atrophic. It is not impossible that there was present a compensatory hypertrophy accompanying degenerative changes in other portions of the gland. The findings resembled those obtained by Halstead in the thyroid of a dog after partial extirpation. It is not improbable that qualitative changes of function of the thyroid gland play a role. Substances, the result of deranged thyroid action, may be formed which may, on the one hand, prevent the proper oxidation of the hydrocarbons of the foods and tissues and on the other may act as a cause of neuritis and nerve degeneration. Whatever the explanation, it is interesting to recall the diminished sweating and the occasional slowness of speech and mental irritability. The interpretation is of course difficult; the obesity and the dryness of the skin suggest thyroid deficienev, while the flushing of the face, the occasional tachy- cardia and the psychic symptoms would point rather to thyroid excess, and it is safer perhaps with Pineles to regard the condition as one of dysthyroidismus. Among the most significant findings, however, are the changes noted in the pituitary bod}'. In five of the six cases in which the pituitary was examined, it was found diseased. Thus Burr described a glioma of the pituitary, Dercum and McCarthy adeno- carcinoma, Guillain and Alquier changes suggesting an alveolar carcinoma, and Price changes likewise suggesting alveolar or glandular carcinoma in two cases. In considering the possible role of the pituitary body, we must bear in mind the recent interesting researches of Harvey Cushing with regard to the carbohydrate function of this organ. It apparently stands in the most intimate relation with the assimi- lation of the carbohydrates so that if its anterior lobe is destroyed in animals, carbohydrate tolerance and assimilation are greatly diminished or lost. The pituitary body is thus brought into relation, though perhaps indirectly with a fat producing or fat destroy- ing function. In the light of other observations, this subject assumes a new importance. Froelich has shown that instead of the symptom-complex termed acromegaly, lesions of the hypophysis may be asso- ciated with an adipositas universalis and genital atrophy. In other words, hypopituitarism may lead to adipositas. Further, curious and remarkable inter- relations of function — seemingly antithetical — appear to exist between the pituitary and the pineal gland, the pineal gland appearing to have a fat producing and a fat destroying function inversely to the pitui- tary. For a detailed presentation of the subject, which here would lead us too far afield, the reader i< referred to Otto Marburg's interesting paper on " Adiposis Cerebralis, a contribution to our knowledge of the pathology of the pineal gland." 5 If the pituitary is diseased in adiposis dolorosa, it is not surprising that changes should also be found in the thyroid; it is unnecessary to point out that these two glands are closely interrelated as regards their function. Experimental extirpation of the thyroid in animals has been found to be followed by pituitary enlargement; it would seem that disease of one gland would mean sooner or later disease of the other. An examination of the fatty deposits reveals not only the structure of fatty tissue, but also the signs of great nutritional activity. Fragments removed during life by the Duchenne trocar in the writer's first case and submitted to microscopical examina- tion presented the appearance of a connective-tissue embryonal in type. The cells were voluminous, fusi- form, and containing large nuclei while the inter- cellular spaces were filled by a transparent substance apparently without structure. On the whole the appearance was that of a lymphoid tissue. In some fragments fat cells were numerous and among these were cells which evidently had not undergone com- plete fatty transformation. In the autopsy recorded by Dercum and McCarthy, the fatty nodules were submitted to microscopical examination. The capsule was composed of several layers of well- developed connective tissue. Within this capsule a looser areolar tissue was met. This tissue was highly vascular, and between the vessels was a reticular tissue, denser in some areas than others and inclosing a large number of mononuclear cells, a few pi nuclear cells, and large numbers of cells stained a tawny color by the Van Gieson stain. Scattered through the granular, tawny masses, many of the mononuclear type of cells could be found. In other areas, granules of blood pigment in clumps could be seen. Wherever the connective-tissue trabecule penetrated into the congested fat nodule, this same fine, reticular structure, holding in its meshes rich plexuses of blood-vessels, and between these a fine reticulum of connective tissue filled with a light yellow granular material, with nucleated yellow cells, small mononuclear cells, polynuclear cells, and num- bers of degenerating red blood cells, could be seen. Some of these cells reacted to many of the staining reagents as do nucleated red blood-corpuscles, but to the Biondi-Ehrlich triple stain they appeared more as mononuclear leucocytes. Diagnosis. — The diagnosis of adiposis dolorosa is exceedingly simple. It is based upon the presence of pain — spontaneous, paroxysmal or elicited by ma- nipulation — in fatty masses having the physical pecu- liarities described above. The affection is readily differentiated from myxedema because of the non- 132 REFERENCE HANDBOOK OF THE MEDICM, SCIENCES Adirondacks juvoh cmenl of Ilii" face .-iml hands and because u! I he absence of pain in myxedema. When the tumor masses arc numerous and quite small, they may suggest von Recklinghausen's disease, i.e. neurofibro- matosis, but the fact that the nodules arc found to be tabulated under palpation, that they are spontane ously painful and almost never occur on the face or hands serves to make the differentiation; again in neurofibromatosis, the tumor masses are only later- ally mobile; they are small, very hard, and often grouped along the course of the nerve trunks like a string of beads. In adiposis dolorosa, the tumors are mobile in all directions and are irregularly distributed. The differentiation between adiposis dolorosa, and simple obesity lies in the fact that in the latter affec- the fat is distributed throughout all the tissues does not heap itself up in separate lipomatous ma ises such as is the case in adiposis dolorosa, oven in the so-called diffuse form. Besides there is an absence both of pain and of crises of any kind. ( Ordinary obesity is painless ami is a matter of gradual development, while the peculiar paroxysmal charac- ter presented by both the pain and the swellings of adiposis dolorosa is unmistakable. Prognosis. — The affection is essentially chronic. It lasts as a rule for many years. Eventually, however, a bedridden period sets in, general exhaustion super- penes, degeneration and failure of the heart muscle, pulmonary congestion, or disease of the kidneys may terminate the picture. It must be borne in mind also that these patients present a greatly diminished resistance to infection. When the affection is in the early stage, the out- look is much less gloomy; indeed at times the prog- nosis is distinctly favorable. Early cases are dis- tinctly amenable to improvement and indeed an arrest of symptoms or relative cure may sometimes be brought about. Cases far advanced, with ex- tensive deposits and presenting marked asthenia and especially when complicated with a tendency to Subcutaneous hemorrhages and hemorrhages from the mucous membranes are very unpromising; indeed, in such cases treatment proves to be of little avail. Treatment. — In cases in which the disease is not too far advanced, the writer has had marked success by employing the following measures. First he places the patient in bed, secondly he withdraws as far as Eossible the carbohydrates from the diet, and thirdly e administers cautiously but in increasing doses, thyroid extract; beginning usually with one grain, three times daily, and increasing to three grains, three times daily — rarely five grains. In order to control the pains, he has made liberal use of aspirin or novaspirin. At times he has fallen back upon sodium salicylate with sodium bromide in full doses, especially during paroxysms of pain. As a rule these measures, if persisted in for several weeks or better still for a number of months, are followed by a marked loss of weight and a marked subsidence of pain. In three of the writer's cases the improvement was both marked and persistent; in two a permanent arrest of symptoms ensued. The rest should be absolute and should extend over several months. The patient should be weighed when treatment is begun, and at intervals thereafter. Jt should be remembered that a diet, no matter how rigid, will of itself make no impression in adiposis dolorosa; it will fail absolutely. It is of course wise to institute a careful diet, but patients do better when the diet is not too strict. Inasmuch as the affection is attended by a marked asthenia, the diet should be nutritious It should consist of the red meats in moderation, the white meats freely, the succulent vegetables, eggs, and skimmed milk. The latter can be used between meals and if necessary also at meal times. As soon as the tenderness permits, gentle massage should be instituted; sometimes this can never be employed, in other eases it can be instituted com- paratively early and there can be no doubt thai in a measure it favors the diminution of the swellings, especially if the patient can bear deep kneading. Bathing between blankets as in ordinarj m i treat- ment should also be carried out, but of themselves baths accomplish nothing in adiposis dolorosa; in- deed the physical exertion and manipulation attend- ant upon the application of ordina ry hydrotherapeutio measures in these cases exhaust the patient. The treatment should extend over a period of many months and the patient should be kept under observation for several years. F. X. Derci m, I: i FEUENCES. 1. Vitaut: Maladie de Dcrcum. Thesede Lyon, [901. 2. Frankenheimer: .tour. Amer. Med. Asso., 1908, i.. p. 1012. 3. Price: Amer. Jour. Med Sciences, May, 1909, 4. Leon Poirier: La Maladie deDercum.MontpelHer, 1910. 5. Marburg: Deutsche Zeitschrift fur Nervenheilkunde, 1908. Bd. xxxvi p. 111. Adiposity. — See Obesity. Adirondacks. — This extensive forest and lake region is a plateau studded with mountains and lakes :d situated in Northern New York, between lat. 42° 30' and I 1 30', long. 74° to 7.5° 30' W., being, roughly e timated, 1 25 miles square. The average elevation is 1,000 feet, the mountain peaks varying from 2,000 to 5,000 feet, trending in general toward the southwest in several irregular ranges. The northern and southern boundaries are gradual slopes to the St. Lawrence and Mohawk valleys respectively, while the eastern is more abrupt to Lakes George and Champlain, and the western less so to Lal^e ( intario. Geologically, this region is related to the Archean or earliest formation, with glacial drift and moraines much in evidence. The soil is chiefly light sand, which forms a feature of importance in determining the climate and character of the forest growth. The lake shores, lowlands, and valleys are wooded chiefly with fir, pine, white cedar, tamarack, red spruce, and balsam. The lesser elevations and foot- hills have deciduous trees in greater proportion, such as sugar maple, birch, beech, poplar, mingled with a few evergreens, while the majority of the peaks are wooded to the top with firs and spruces. The combination of dark-green-clad mountains and numerous island-dotted lakes gives at all seasons a landscape of great beauty. Large tracts of forest are owned by the State and individuals for permanent preserves, insuring pro- tection for fish and game and conserving the water supply. Temporary camps are permitted on Stale land, and during the trout and deer seasons great numbers of sportsmen find delight in these haunts. Modern camp life for the invalid or convalescent in the Adirondacks is a pleasure hardly surpassed, when all the luxuries are available. The climate has long been noted for its invigorating qualities. The winters are usually cold and dry, the summers cool but moist, though relatively dryer than coast climates or lowlands. The porous soil, elevation, and coolness render the moisture less apparent, though the rains are very fre- quent in summer. Meteorological data for a number of years are now available for the comparison of different sections of the plateau. The mean annual temperature for the whole region is 42. s° F. ; average total precipitation, forty-two inches. The prevailing winds are west and southwest, being much varied and retarded by the mountains and im- mense areas of forest. The coast winds do not reach inland far enough to affect the climate, but Lake ( intario modifies the western slope, while the northern part is influenced more by the St. Lawrence valley 133 Adirondacks REFERENCE HANDBOOK OF THE MEDICAL SCIENCES winds, which, especially in winter, sweep across the level plains of Canada from the west. The precipitation is greater on the southern and western slopes than in the interior and northern portion of the Adirondack plateau, though local con- ditions appear to influence the amount greatly. Thus at Saranac Lake, in the northern center, the average annual precipitation is thirty-four inches, yet in the foii'st, within a few miles, it is manifestly much greater. At the same place the annual mean tem- peral lire was 41.7° F., and for the four winter months 19.5° F., with an average of ten rainy days for the winter. The mean summer temperature was 62° F. Quoting from the Annual Report of the New York Weather Bureau, 1896: "The Adirondack plateau is subject mainly to the same influences which deter- mine the climate of the St. Lawrence valley, excepting that the central and eastern portions of the highlands are not reached by the lake winds. A very broken and heavily timbered surface offers great obstructions to the circulation of air currents, and hence the summer temperature, although the- lowest in the State, is somewhat higher than would otherwise be, due to the elevation of the region. ***** " So far, then, as present records show, the whole of Northern New York has substantially the same average winter temperature, except as certain deep valleys are subject to a local cooling through an accu- mulation of the colder and denser air. In summer the warmth of the highlands decreases at about 0.3 degree per hundred feet of elevation above sea level, and the average temperature of the Adirondack region at that season is thus reduced to nearly the same level as that which prevails on the seacoast of Northern Maine; the days, however, being wanner and the nights cooler than in the coast region." There is an excess of cloudy weather in November, December, April, May, and frequently at other seasons; the virtues of the climate being attributable to coolness, altitude, aseptic atmosphere, and freedom from dust, rather than to the amount of sunshine. The suitability of the climate for the cure of early tuberculosis has been amply demonstrated, and arrest or amelioration of advanced cases is secured by a prolonged residence, when the powers of resistance can be stimulated. It has been found beneficial, particu- larly in summer, for chronic bronchitis and asthma dependent upon it, also for hay fever. The winter is equally good, if not better, for early tuberculosis. It is unsuited for rheumatics, renal cases, and patients beyond middle life. The principal resort, Saranac Lake, is generally known because of the Adirondack Cottage Sanitarium, founded by Dr. E. L. Trudeau, for tuberculous patients of moderate means. This establishment has one hundred rooms, and was the first people's sana- torium of its kind in America. Twenty-five per cent of all cases and from sixty to seventy-five per cent, of the incipient class are discharged apparently cured. A list of the various resorts in the Adirondack region with their respective elevations, is appended. Further information can be found in Solly's " Medical Climatology," in Knopf's "Pulmonary Tuberculosis," in nuicis book , etc. Resort. Elevation. Mini,- Lake 1,535 feet. Lake Placi.l 1,863 feet. Tupper Lake 1,546 feet. Keene 1,000 feet. I llizahethtown 759 feet. Old Forge 1,684 Fei t full, in Chain 1,700 feet. Paul Smith's 1,623 feet, Saranac Inn 1,560 feel. North Elba 1,68 i Chazy Lake 1,500 feet. Blue Mountain Lake 1.S00 feet. Schroon Lake 806 feet. During the past ten years numerous public and private institutions have been established in and about Saranac Lake. The most important are the New York State Hospital for Incipient Tuberculosis situated at Raybrook, two miles east of Saranac Lake; capacity, 350; free to residents of New York State. Stony Wold Sanatorium, Lake Kushaqua, N. Y. ; women and children; capacity, 100; semi- charitable. Sanitarium Gabriels, Gabriels, N. Y.; capacity, sixty; semicharitable. E. R. Baldwin. Adolescence. — The term adolescence denotes that portion of an individual's life, vegetal or animal, during which it is becoming adult or mature. The Latin term adolescere seems to have been allied to alere, to nourish, and this idea still enters the general notion of adolescence as the period of growth and full development. For the majority of English-speaking people, at least, this term covers the period between the ages of fourteen and twenty-five in males, and in females twelve and twenty-one. It includes therefore puberty and years following puberty until the menial and physical aspects of the adult may reasonably be said to have become complete. Individual differences are, however, here as uni- versally elsewhere, conspicuous, and the practitioner is bound to keep in mind the well-known fact that any particular patient may be either precocious or re- tarded. These differences appear on the surface of the literature to be more common in girls than in boys, for many instances of sexual maturity, as indicated at bast by menstruation, fully developed breasts and other sexual organs, etc., have been reported in indi- viduals only a few years or even a few months of age. Retarded adolescence is probably still more common but with far less disastrous results usually to the future happiness of the woman. The physical signs of puberty and later adolescence are generally so conspicuous that little chance of harmful error in any bodily direction normally exists. In those rarer eases, however, in which the mental efficiency ami capabilities are uncorrelated to the physical evolu- tion, mistakes with unfortunate consequences are liable to be made by teachers and by parents. This diseorrelation is a subject that needs scientific study. As writers have pointed out repeatedly, this pre- eminently important whole period of life, likewise, has as yet received but a small part of the study and research it deserves; but there are indications that physiologists, psychologists, and hygienists are at last awakening to their dutiful privilege in this respect. President G. Stanley Hall is the one conspicuous exception to this generality, so much so indeed that his treatise ("Adolescence," 1907) is likely to remain for some years yet the magnum opus in this particular scientific field, much as is Havelock Ellis's "Psy- chology of Sex," in that somewhat closely allied sub- ject. The present writing is much indebted to both of these compendiums, especially to the former, ami to them the reader is respectfully referred for greater wealth of detail and statistics. If one search the medical libraries for adequate information on the physiology and pathology of adolescence, one will he properly surprised at the contrast between the abun- dance of publications on childhood and their paucity in relation to the no less important developmental con- ditions of adolescence. One of the pressing needs in medical literature is a really adequate exposition of this subject detailed with special reference to every phase of the professional theory and practice; this would afford one more set of adaptations of the general principles of Medicine to particular con- ditions. Somatology. — It is customary in discussions of 134 REFERENCE HANDBOOK OF THE MEDICAL SCIENI I 3 Adolescence puberty to devote considerable care and space to the tabulation of statistics on growth, growth of tissues, of organs, and of Individuals, sel forth in about every useful way both in absolute numbers and in percental relationships. So frequently of late have summaries of these averages been published in many kinds of books that it seems unnecessary to reproduce them at length. Stanley Hall speaks of about sixty such iv valuable memoirs and tabulations" of growth. for a summary, F. Burk: American Journal of hology. April, 1898, pp. 253-326.) As respects stature, the table made out by Prof. Franz Boas of Columbia from his own measurements and those i Bowditch, Porter, Peckham, and West, of 45,151 boys and 43,298 girls resident in Boston, St.Louis, Milwaukee, Worcester, Toronto, and Oakland, is of fundamental value and is, therefore, here repre- d as the American standard at the ages repre- sented: Growth Number at each age Height Weight Vgi Actual, . ental in nun ■ in kilns hut' 16 30 37 . 23 2 15 8.01 1 I..-.1 17 I ;i 2 ) 76 1.15 18 211 0.70 1 . 56 7. 11 19 153 7 99 3.18 5.49 20 73 7.69 0.50 5.29 21 •1!) 6 in 0.34 2 s7 5.60 22 27 5.22 , , 23 12 1.92 0.26 3 . 1 5 21 13 0.16 1 . 92 3.02 25 i 1.28 2.42 6.18 12.76 .71) 1.19 8 l-'i Boys. lirls. Approxi- mate average Number of Average height Absolute an- Percental Number of '■• height Absolute an- Percental observations for each year, nual increase, annual observations ch year, nual increase. annual • inches. inches. increase. inches. inche increase. .". . ') 1 ,535 41.7 2 . 5.3 1,260 41.3 2.0 4.8 6.5 3,975 43.9 2.1 l.s 3.61S 43.3 2.4 5.5 i ..> 5.379 46.0 _' s 6.1 4.913 45.7 2.0 4.4 8 . 5 5,633 IS S 1.2 2.5 5.2S9 47.7 2.0 4.2 9.5 5,531 50.0 1.9 3.8 5,132 49.7 2.0 4.0 5,151 51 . 9 1.7 3.3 1,827 51.7 2.1 4.1 ll.. r ) 1,759 53.6 l.S 3.4 1,507 53.8 2.3 4.3 12.5 I.-' 15 55.4 2.1 3.8 4,187 56.1 2.4 4.3 13.5 3,57) 1 ..» i . . » 2.5 4.3 3.411 58.5 1.9 3.2 14.5 2,518 60.0 2.9 4.8 2,537 60.4 1.2 2.0 15.5 1.481 62.9 2.0 3.2 1 ,656 61.6 0.6 1.0 16 5 753 64.9 1.6 2.5 1.171 i.J J 0.5 O.S 17.5 129 66.5 0.9 1.4 790 62 . 7 229 67. t As concerns weight, Burk's table, made from the weighing of 69,000 children in Boston, St. Louis, and Milwaukee by* the same observer-, is as follows: The relative sizes and activities of the various tissues and organs characteristic of adolescence, although of importance to the physician very often Boys. Girls Age Average for each \ 1 isi ilute annual Percental annual Average for each Al isolute annual Percental annual age, pounds. increase, pounds. increase. age, pounds. increase, pounds. increase. 6.5 45.2 43.4 7.5 49.5 4.3 9.5 47.7 4.3 9.9 8.5 54.5 5.0 10.1 52.5 4.8 10.0 9.5 59.6 5.1 9.3 57.4 4.9 9.3 10.5 65.4 5.8 9.7 62.9 5.5 9.6 11.5 70.7 5.3 8.1 69.5 6.6 10.5 12.5 76.9 6.2 S.7 78.7 9.2 13.2 13.5 84.8 7.9 10.3 ■s.S.7 10.0 12.7 14.5 93.2 10.4 12.3 9S.3 9.6 11.9 15.5 107.4 12.2 12.8 106.7 S.4 S.5 16.5 121.0 13.6 12.7 112.3 5.6 5.2 17.5 115.4 3.1 2.8 18.5 114.9 The late Professor Edward Hitchcock of Amherst College, the American pioneer in this work and in other work relating to physical education, measured T4J different students (males), at that institution, belonging to the classes between 1885 and 1901 and summarized the results as in the following table. This obviously is complementary to the preceding tables, for it takes the development to the full limits of the time of average adolescence for purposes of accurate diagnosis and the general understanding of conditions, is too long and compli- cated a matter for insertion here, consisting as it does of very numerous facts and statistics from which it would be difficult to choose. Stanley Hall's monograph already referred to contains the most complete exposi- tion of the subject known to the present collaborator, occupying seventy-eight pages of the first volume of the work; to this compilation the reader is referred. 135 Adolescence REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Psychology. — The mental characteristics of the adolescent receive everywhere extensive description, of course, incidentally in fiction, and have been dis- cussed more intensively but unsystematically by many competent scientists, and of late still more technically through knowledge gained by the new method of psychoanalysis. None of the scientific accounts is truer to the life than that of G. Stanley Hall and therefore we shall not hesitate to quote from him, first reminding the reader that many of these psy- chological considerations, some of them general and hard to analyze as they are, are of preeminent impor- tance in medical affairs of many kinds, somatic as well as those more psychical in classification. In adoles- cence, fully as much as elsewhere in the life time, bodily and mental relations are interdependent and inseparable, neither being fully understandable with- out knowledge of the other, for each is part and par- cel of one indivisible personality. It is high time the medical profession put this basal fact, so fully realized as true by every observant and educated student of humanity, into practice and used it habitually as a principle of diagnosis and of treatment, as already indeed do the most broadly educated of our physicians, more and more. Nowhere more than in adolescence i- this interdependence of dependent variables con- spicuous and important, both mind and body being then eminently plastic and impressionable to stimuli within and without. "Psychic adolescence," says Stanley Hall, "is heralded by all-sided mobilization. The child from nine to twelve is well adjusted to his environment and proportionately developed; he represents probably an old and relatively perfected stage of race maturity, still, in some sense and degree feasible in warm cli- mates, which, as we have previously urged, stands for a long continued one, a terminal stage of human devel- opment at some post-simian point. At dawning adolescence this old unity and harmony with nature is broken up; the child is driven from his paradise mil must enter upon a long viaticum of ascent, must con- quer a higher kingdom of man for himself, break out a new sphere, and evolve a more modern story to his psychophysical nature. Because his environment is to be far more complex, the combinations are less stable, the ascent less easy and secure; there is more danger that the youth in his upward progress, under the influence of this excelsior motive will backslide in one or several of the many ways possible. New dangers threaten on all sides. It is the most critical stage of life, because failure to mount almost always means retrogression, degeneracy, or fall Youth loves intense states of mind and is passionately fond of excitement. Tranquil, mild enjoyments are not its forte. The heart and arteries are, as we have seen, rapidly increasing in size, and perhaps heightened blood pressure is necessary to cause the expansion normal at this stage. Nutritive activities are greatly increased; the temperature of the body is probably a trifle higher. After its period of most rapid growth, the heart walls are a little weak, and peripheral circu- lation is liable to slight stagnation, so that in the interests of proper irrigation of the tissues after the vascular growth has begun, tension seems necessary. Although we do not know precisely the relation be- tween blood pressure and the strong instinct to tingle and glow, some correlation may safely be postulated. Ii is the age of erectile diathesis, and the erethism that is now so increased in the sexual parts is probably more or less so in nearly every organ and ti- lie The whole psychophysic organism is expanding, stretching out, and proper elasticity that relaxes and contracts and gives vasomotor range is coordinated with the instinct for calenture or warming up, which is shown in phenomena of second breath in both phys- ical and mental activity. In savage life this period is marked by epochs of orgasm and carousal, which is perhaps one expression of nature's effort to secure a 136 proper and ready reflex range of elasticity in the cir- culatory apparatus. The "teens" are emotionally unstable and pathic. It is the age of natural inebria- tion without the need of intoxicants, which made Plato define youth as spiritual drunkenness. It is a natural impulse to experience hot ami perfervid psychic states, and is characterized by emotionalism. We here see the instabity and fluctuation now so characteristic. The emotions develop by contrast and reaction into the opposite. We will specify a few of its antithetic impulses now so marked. 1. There are hours, days, weeks, and perhaps months of overenergetic action 2. Closely con- nected with this are the oscillations between pleasure and pain — the two poles of life, its sovereign masters. The fluctuations of mood in children are rapid and incessant 3. Self-feeling is increased, and we have all degrees of egoism and all form- of self-affirmation. ..... 4. Another clearly re- lated alternation is that between selfishness and altruism 5. Closely connected with the above are the alternations of good and bad conduct generally 6. The same is true of (he great group of social instincts, some of which resl upon the preceding. Youth is often bashful, retiring. in love with solitude 7. Closely akin to this are the changes from exquisite sensitiveness to imperturbability and even apathy, hard-hearted- ness, and perhaps cruelty .s. Curiosity and interest are generally the first outcrop of intel- lectual ability. Youth is normally greedy for knowl- edge, and that not in one but in many directions. 9. Another vacillation is between know- ing and doing. Now the life of the study chant -. and the ambition is to be learned, bookish, or there is a passion to read. He would achieve rather than learn 10. Less often we see one or more alternations between dominance by conservative and by radical instincts 11. We find many cases of signal interest in which there is a distinct reciprocity between sense and intellect, as if each had its nascent period 12. Closely connected with this is the juxtaposition of wisdom and folly We have already seen that the body growth is not symmetrical, but to some extent the parts, functions, and organs grow in succession, so that the exact normal proportions of the body are temporarily lost, to be regained later on a new plan. The mind now grows in like manner. It is as if the various qualities of soul were developed successively; as if the energy of growth now stretched out to new boundaries, now in this and now in that direction." This quotation from a master of the subject is justified in the extreme importance of this aspect of the adolescent individual — preeminent over the body, often in directions to which the physician desires to turn his attention more and more each year as he gradually learns better how indivisible is the psycho- physical nature of mankind. Nowhere else, certainly, than in adolescence has the mind, its feelings and its thoughts, stronger dominance over the somatic phases of the evolving life — over nutrition, circula- tion, reproduction, movement, secretion, the bodily half of us all. Later in life, body, as it hardens, tends more to dominate mind, but in adolescence ii i< eminently impressionable to every mental influence. We have repeated it for emphasis, for it constitutes the keynote of all real understanding of adolescei Another inherent factor that must be noted con- cerning this period of life is somewhat related to this one — we refer to the rapid growth and evolution and activity of the two-phased individual. This vivacity of the whole being, both as protoplasm and as com- plete animal, both as body and as mind, makes the youth or maiden, as compared with the child or the adult, much more apt to go astray off the beaten I nek of the average, of the so-called " normal." In a some- what metaphorical sense, it is a irmtter of momentum. i;i:i i;i:i:\ci: ha.xuhook of Tin: mfdicai. sciences Adonis Just as a rapidly moving oar meets usually with worse disaster when il leaves the rails than does one moving slowly, so many adolescent conditions, verging at [ea i on the aberrant, become conspicuous and often distinctly pathological, because of the rapid changes going on in the living tissues and in the mental action oi the adolescent. Perhaps the most conspicuous illustration of this tendency is to be seen in the distortions of the skeleton (mentioned below). l'.v iiiot.oov. — We have already noted the paucity dual descriptions and discussions of the diseases, mental and bodily, of adolescence. One reason for tins has been the obvious fact, borne out alike by general medical observation and by elaborate sta- tistics, that while the morbidity of adolescence is large, larger than thai of any other parts of life early infancy and senescence, the mortality of this period is low, in fact the lowest of the whole life, especially between eleven and fifteen (Hartwell). Another important reason of this widespread medical defect in the study of adolescence has been stated by Hall concisely in these terms: "The general reason for this neglect is that medicine has been chiefly concerned with the study and practical treatment of pronounced diseases, and has not yet come to rest on the broad basis of biology, which is its natural and scientific foundation. Practitioners, too, have been occupied, both at home and in hospitals, with grave cases and have had little time and less motive to CorTsider preventive medicine or the more general problems of regimen and hygiene, personal, domestic, or public. Perhaps occupation with flagrant symp- toms tends to give diminished interest, if not distaste, for the milder and incipient manifestations of disease which require sharper diagnosis and a higher quality of mind to detect." This is wisdom of the highest practical and theoretic importance, but these con- ditions of defect mentioned are now certainly in process of elimination from all adequate medical education, for biology is rapidly becoming the mother- science of scientific medicine. (See for example the writer's recent pioneer "Laboratory Course in Phys- iology based on Daphnia and Other Animalcules," in the Biologische Zentralblatt, Bd. xxxii, Nr. o. S. 285 291, May 20, 1912). One large part of the pathological conditions of adolescence is commonly thought and discussed as "functional" defects, those especially that depend ultimately on maladjustment to the rapid evolution of mind and body and which more immediately are obviously conditions only a little beyond fatigue coming from overuse. Examples of this that will occur to every reader are chlorosis, eyestrains, and kyphosis (roundback). t If the diseases which are most common during adolescence many are chronic conditions that reach their worst later on in adult years. Others are com- mon to childhood and adolescence — holdovers, as it were, from their more proper and earlier epochs when the susceptibility' or liability to them is greater. No classification of the diseases of adolescence is adequate owing to the perfect unification of the psychophysical nature of man, but it might be con- venient, none the less, to divide them into classes more or less corresponding to the physiological sys- tems of the individual. We should then have groups of infectious fevers; of blood and circulatory diseases; of joint and skeletal diseases; of digestive and meta- bolic diseases; of nervous diseases; of skin diseases; and of genital diseases. The infectious fevers most often seen in adoles- cence, perhaps, are pulmonary tuberculosis in the acute form, rheumatic fever, typhoid fever, acute anterior poliomyelitis, rotheln (German measles), diphtheria, mumps, and meningitis in all its forms. Of these typhoid fever is at its worst in adolescence, and the life-ravages of acute rheumatism on the heart- valves are beyond computation in many parts of the world. It should be noted that poliomyelitis, although most unfortunately railed infantile paralysis, in the recent widespread epidemics has frequently attacked adolescents, their susceptibility being probably under- estimated by the profession as well as by the laity, in part perhaps owing to its old-time name. The bl 1 and circulatory diseases, perhaps d conspicuous between the ages of tweh e and twenty- three, are simple anemia, chlorosis, albuminuria, acute myocarditis, endocarditis, tachycardia, arrhyth- mia, brachycardia, palpitation, pharyngomyeosis, lymphadenitis, epistaxis, and edema "I the larynx Of these the anemias are the most characteristic of adolescence. Among the numerous conditions of joint at id bone disease seen most frequently at the age which we are discussing, are scoliosis, kyphosis, genu valgum, genu varum, pes planum, acroiliac disea e, tuberculosis ossium, chondr a, acromegaly, giga tism, infantilism, and the rickets of adole cence. Metabolic diseases proper I the class is a very indefi- nite one by its nature) peculiar to adolescence do not exist, but among those most commonly met with perhaps, in addition to those already noted, are myx- edema, goiter, exophthalmic goiter, diabetes insipi- dus, and Addison'.- disease. Abnormal conditions related to the digestive apparatus more or less directly, seen in adolescents, are dyspepsia, gastric dilatation, enteroptosis, gastralgia, floating kidney, gastric ulcer, appendicitis. The nervous diseases are numerous and important, as might be expected from the unbalancing effects of the strains and stresses incident to the rapid changes and violent emotions of this period of life. Neuras- thenia, cephalalgia, epilepsy, catalepsy, hysteria, chorea, spasmodic asthma, "psychic infantilism," acute dementia, early stages of syringomyelia, demen- tia precox, cerebral embolism, spinal apoplexy, Friedreich's disease, cerebellar ataxia, spasmodic spinal paralysis, are among the most, important. The skin diseases of adolescence are of no little practical importance, being very common, some of them, indeed. Acne in various forms, eczema, urticaria, psoriasis, keratosis, lupus, furunculosis, verruca vulgaris, seborrhea are among the most conspicuous of these. Gonorrhea and syphilis are, of course, the most important of the genital diseases of adolescence, with import for the human race scarcely yet appreciated, even by our profession. In closing this brief outline of this significant period of life, one of the most interesting from every point of view, the extreme importance of the new awakening in sexual common knowledge of all kinds, and in eugen- ics as its outcome, cannot be too strongly urged. In this direction lies apparently one of the physician's most splendid opportunities, for the very root of adolescence is the sexual evolution and sexual maturity. George V. N. Deaeborn. Adonidin. — Adonin. A glucoside obtained from several species of Adonis, chiefly from the root of A. vernalis L. It is a light-yellow powder, without odor, but intensely bitter, very hygroscopic, soluble in both water and alcohol. Moisture must be carefully ex- cluded from the containers. As it exists in commerce, it is a mixture of variable degree of purity. Its action is described under Adonis. The dose is 0.004 to 0.016 gram (grain T V to \). Picradonidin is merely the very pure form of adonidin. H. H. Rusby. Adonis. — False Hellebore (family Ranunculaeecc). The carefully dried and preserved herb of Adonis vernalis L., one of some sixteen species in the genus. It is a small plant, growing wild in Southern 137 Adonis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Europe, and somewhat cultivated as an ornamental flower. Owing to the instability of its active con- stituent, adonidin, it should be carefully preserved in a cool and dry place and should not be kept on hand too long. The plant is poisonous. Besides the active constituent described above, it contains aconitic acid to the extent of ten per cent. The action of adonis is apparently due altogether to the adonidin, which exists to the extent of 0.02 of one per cent. Its effects are for the most part exerted upon the circulation. Its first and chief action is to stimulate the vasomotor centers and thus greatly increase blood pressure. Next it stimulates the heart directly, increasing both its rate and force, and thus still further increases the blood pressure. This pressure then reacts against the heart and may slow it. If the dose is larger, the inhibitory centers are stimulated, and this markedly slows the heart. The same causes render it a powerful indirect diuretic. The vasomotor stimulation is not long continued, and is succeeded by depression, as is to a less extent the direct cardiac stimulation, the two together causing a sudden fall in blood pressure. If the dose is a poisonous one, death will occur with the heart in diastole. Large poisonous doses cause vomiting and purging. The treatment of poisoning is entirely physiological and symptomatic and is practically the same as in digitalis poisoning, except that the stage of reaction may be expected much more quickly. Adonis is used in exactly the same way as digitalis, as a cardiac and arterial stimulant, and is liable to the same contraindications. The greatest difference of opinion exists as to which is preferable, but it appears established that adonis, at least in the form of adonidin, acts more quickly, though the action is not so prolonged, and is more apt to be followed by reaction. No attempts have been made to ascertain whether the tissue of the heart muscle is permanently changed in quality or quantity by adonis, as appears to be the case with digitalis. Adonis is best given in the form of tincture or fluid extract, which are miscible with water, or :is adonidin. The dose of adonis should represent 0.05 to 0.25 gram (grain i. to iv.). It is best to begin with a small dose and increase gradually. H. H. Rushy. Adrenal Glands. — See Suprarenal Glands. Adrenalin. — Trade name of a substance derived by Aldrieh and Takamine in 1901 from the suprarenal glands of the ox, and containing the active principle of the internal secretion of these glands. It has the empirical formula C 10 H 15 NO 3 (Takamine) or C 9 H 13 - NO, (Aldrieh), and occurs as a grayish or light brown finely crystalline powder, of a somewhat bitter ami benumbing taste, slightly soluble in w-ater, insoluble in alcohol, ether, and chloroform. The form in which it is commonly used is the solution of adrena- lin chloride, which is a 1-1 000 solution of adrena- lin chloride in physiological salt solution, with the addition of 0.5 per cent, of chloreton. For a de- scription of the physiological action and therapeutic uses of this and other adrenal gland extracts see Epinephrin and Suprarenal glands. Aedinae. — A family of mosquitos, Culicidce, in which there is a straight proboscis, short palpi in both sexes, plumose antenna? in the male and pilose in the female. The mosquitos of the genera in this family are usually found in jungles, and they are suspected of being hosts of the malarial germ and also carriers of Filaria es- pecially F. perstans. See Insects, poisonous. A. S. P. Aegidius Corboliensis, Petrus. — Pierre Gilles de Corbeil, as he was known in France, was born in the twelfth century. He studied medicine at Salernum, in Italy, was the regular medical attendant of Philip Augustus, and was a professor in the Medical Faculty of Paris. His writings on various medical topics (on the urine, on the arterial pulse, on compound drugs, and on the signs or indications of disease) were gener- ally accepted, for a long period of years, as of the highest authority. Printed editions were issued at Padua Mist), at Venice (1494), at Lyons (1505, 1515, 1526), and at Basle (1529). Some idea of the import- ance attached to the writings of Aegidius may lie formed from the fact that an entirely new edition of the first three works mentioned above was printed at Leipzig as recently as in 1S26. A. H. B. Aerophagy. — Aerophagia, from ii/p, air, +4>iyw, 1 eat. This term has come into general use quite recently, not being mentioned in Gould's Dietianary of 1904, though frequently encountered in periodicals early in the present century. It is, however, practi- cally identical with the habit of cribbing in horses, long and well known, and under various designations has been described in human beings for many years. For the most part, however, it has been confused with ordinary belching of gas formed in the stomach. The inclusion of some air in food, drink, and secre- tions swallowed is inevitable, especially during hasty eating and drinking and in continued, forcible attempts to clear the throat of mucus. The amount included seems to depend upon the conformation of the fauces and pharynx. The subsequent belching of at least part of the air thus swallowed is a normal, conservative process. True aerophagia is a habit neurosis of two quite distinct types: (1) The literal swallowing of air and its subsequent eructation; (2) an inspiratory spasm with closure of the glottis — hiccough or singultus— with the added feature that for some unexplained reason, the esophagus becomes patulous and dis- tended under the thoracic suction due to the action of the diaphragm and extrinsic muscles. The inclusion of the second type is justified, partly because the essential pathological element is the habit and the symptoms are similar; still more because of the gradual transition from the former to the latter type through (a) the combined (obviously not syn- chronous) occurrence of swallowing and sighing; \l>) the interruption of the sigh by a closure of the glottis; (c) the suction of air into the esophagus almost without deglutitional movements. Normal aerophagia implies the entry of air into the stomach. Whether air enters the stomach or not in the first type of pathological aerophagia, depends on the distensibility or actual dilatation of the esophagus (the last a rare complication), and the length of the deglutition stage. The patient, almost always — and the physician often — is unaware of this stage and hence regards the condition as an eructation of gases developing in the stomach itself. Cases in which only one or two swallows are taken, followed by the eructation of a mouthful (approximately fifty cubic centimeters) of air, do not usually furnish deglutition sounds at the cardia and probably no air reaches the stomach. When the two stages are both prolonged auscultation usually shows that air enters the stomach and, even if this sign is absent, a large quantity of air must have been thus stored, unless the esophagu- is considerably dilated. The more closely cases approach the second, singultic, type, the less likelihood is there of penetration of air into the stomach. The question must, therefore, be determined for each case and it must not be forgotten that as there is always con- siderable gas developed in the intestine and not very rarely in the stomach, the aspiration and expulsive efforts of both types of aerophagia are apt to be complicated by true belching. The diagnosis, which is mainly a matter of differ- 138 REFERENCE HANDBOOK OF THE MEDICAL SCIEN( I - Aerothempeutlcii entiation from ordinary belching in the first type :unl from hiccough withoul esophageal distention in the second, rests on the following points: (1) Careful observation of the muscular action, elevation of the thyroid, etc.; ('-') Estimation of the amount of gas eructated as by merely noting the duration of an attack, by collection in some simple form of trap, as a glass inverted over a basin of water, etc.; (3) auscultation over the pharynx, esophagus, anil stomach; (4) inhibition of the phenomenon by closure of the month or nares or both. ASrophagia is probably always essentially hyster- ical, though not necessarily to the extent of involving moral perversion or manifestations in other more eral ways. The exciting cause may be almost any emotional or physical disturbance; or, as usually in cribbing horses, the phenomenon occurs in periods of quiet and is interrupted by any form of activity or by the same causes that, in other in- stances, act as excitants. To some degree, a great variety of organic or functional disturbances may ad, at times as predisposing, at others as exciting causes. Nasal polypi, any throat lesion of an irritating nature, chronic colitis, pelvic disease, gallstones, movable kidney are mentioned with special frequency. fermentative dyspepsia and hyperchlorhydria with its irritation, usually falsely ascribed to the pressure of gas in the stomach, sometimes genuinely accom- panied with gas due to the interaction of gastric and upper intestinal contents (carbon dioxide) logically lead to esophageal reflexes and hence occasionally to rophagia. From the nature of the underlying exciting and predisposing causes, it is scarcely essary to state that women are more often affected. Treatment. — Removal of these various causes and antispasmodic and general hygienic treatment are indicated, but often fail. It is important that the patient understand the mechanical, if not the neurotic ors involved. Drinking water, a light luncheon, gargling the throat, shutting the lips tightly, and if — ary the nostrils, interrupt the actual aerophagia, but do not necessarily either terminate the attack or produce a cure. The result obviously depends on personal factors, notably the duration and fixity of tla' habit and the degree of self control, spirit of cooperation, or contrariness of the patient. The passage of the stomach tube or esophageal bougie almost always accomplishes a cure, if persisted in, partly by the effect of massage in diminishing spasm, partly from dread of reintroduction of the tube. Local analgesics to the throat, applied on the esophageal sound or injected through the stomach tube into the esophagus, thermic and various electric forms of treatment are also of value, probably more by increas- ing the force of suggestion than by direct therapeutic effect. A. L. Benedict. Aerotherapeutics. — The term "aerotherapeutics" is employed with varying significance by different writers: thus, for example, Williams' uses the term as the application of climate in the treatment of lung disease; others apply it to the use of air artificially attenuated or compressed by various mechanical devices, such as the pneumatic cabinet. (See Pneu- matotherapy). Here, however, the term will be used in the more simple sense, as the application of plain outdoor air in the treatment of disease. Since the open-air treatment of pulmonary tuber- culosis has become so universal and the results there- from have been so striking, the attention of the physician and surgeon have been directed to its use in the treatment and hygienic management of other forms of tuberculosis, notably surgical, as well as in ether non-tuberculous diseases. Not only in diseased conditions but in health as well the cult of the outdoor life, if it may be so denominated, has become popular, and the sleeping porch and outdoor living room are often in evidence; ami it i.^ generally acknowledged by those who have accustomed themselves t<> open- air conditions, whatever the Season of the year, that, the genera] health is thereby maintained at a higher standard, sleep is more refreshing and colds and other infections tire less frequent. The literature upon the subject of fresh air and its application has grown apace, and lie- attention of h" pita] and school authorities, health boards, factory inspectors, architects, as well as physicians and sanitarians have been increasingly directed to its importance. "If fresh air," they say, "is SO valuable for the sick, it must be equally valuable in keeping a man well." There is hardly a disease or abnormal condition which is not benefited by the open-air treat m«nt; preeminently so are the various forms of tuberculosis, pneumonia, anemia, and var- ious conditions of depressed vitality, which, unless they receive timely remedy, may result in active tuberculosis. It is to be understood, and this must be emphasized, that the open-air treatment means out of doors, or as near an approximation to it as can be obtained, and in speaking of fresh or pure air, out of door air is meant. Of course, no air practically obtainable is absolutely pure. Generally, out-of-door air must be that supplied in the place or locality where the patient is or has to be. If, for example, he is ill with pneumonia in a city, he can only have as good outdoor air as the city affords. We can, as we do in many instances, send patients to various health resorts — in the mountains, on the sea-shore or to other climatic- ally favorable localities for the purpose of obtaining purer air than can be found at home; or for obtaining a peculiar variety of air, like the rarified air of the mountains or the salt-impregnated air of the ocean; or for other especial climatic characteristics desired; or, again, because outdoor air can be had under more agreeable conditions, as, for example, in the warmer latitudes during the colder months of the year. Nevertheless, open-air comparatively fresh and active, or at least that which will serve our purpose, can be obtained, fortunately, almost every- where, for the majority of invalids cannot go far afield to seek it. The roof of a city house, the piazza of an apartment, a shack or tent in the yard, a window tent, and many other devices will furnish it; or we can approximate to open-air conditions in large rooms, with windows on two or more sides and an open fireplace. It must also be borne in mind that the therapeutic application of the open-air treat- ment must be directed in the same careful and pains- taking way as with other therapeutic measures, and hence be under the direction and supervision of the physician. In this article the open-air treatment will be con- sidered in its application to: (a) Pulmonary tuberculosis. (b) Surgical and other forms of tuberculosis. (c) Pneumonia and other infectious and respiratory diseases. (d) Various conditions of malnutrition, anemia, and other dyscrasias. (e) Organic diseases. Pulmonary Tuberculosis. — The so-called "open- air" treatment of pulmonary tuberculosis is the established treatment of this disease at the present day. In a word, it consists in affording the patient pure outdoor air to breathe continuously, both night and day, keeping him out of doors by day and having his bedroom windows open by night, or better having him sleep also out of doors. It is hardly necessary to add that at the same time due attention should be paid to diet, rest, hydrotherapy, and to all that pertains to the hygienic well-being of the patient; hence this method is also, and perhapsmore correctly, termed the "hygienic-dietetic" treatment. This treatment has been brought to such a degree of 139 Aero therapeutics REFERENCE HANDEOOK OF THE MEDICAL SCIENCES perfection that it may almost be said to be independ- ent of climate; that is, it can be successfully carried out wherever there are pure air free from dust, protection from wind, and a moderate amount of SU nshin< — climatic conditions which are obtainable almost everywhere outside of large centers of popula- tion and even there it can successfully be carried out, as is constantly exemplified in tuberculosis classes and otherwise. It seems a very simple matter to conduct such a treatment, but experience has shown that constant supervision is necessary, aided by the example of others, in order to keep the patient up, day after day, summer and winter, to this treatment in all its strenuousness; hence the great value of sanatoria and their constant and rapid increase in number. Even though this treatment is in a measure independent of climate, it is not to be asserted that all climates are equally valuable, for it is obvious that the greater the number of favoring climatic elements, the more perfectly the treatment can be conducted, and the more successful it will be. Hence such resorts as Davos, Colorado Springs, California, Asheville, the Adirondacks and many others of superior climatic excellence are especially favorable for this mode of treatment, provided the other essential factors, such as diet, etc., are at hand. It may be thought that this treatment can be accom- plished by simply instructing the patient to keep out of doors; nothing could be more fallacious than this. In the first place, the patient, in many cases, will not keep out of doors all day of his own volition. If he is out for a few hours each day, he is prone to think that he is fulfilling his instructions. Further, he is too often left to himself to determine whether he shall remain at rest or take exercise while in the open; generally he does the latter, sometimes from ignor- ance, sometimes for the want of any proper place where he can remain at rest. Here, again, comes in the value of the sanatorium where all these details are carefully looked after. The theory of the outdoor treatment in this disease is, of course, evident; the object is so to improve the nutrition of the pulmonary tissue and general system, and so to harden the patient and thereby increase his resisting power that he will no longer present a favorable soil for the tubercle bacillus. It is also claimed for this treatment that it will increase tissue metabolism, so that fibroid transformation of tuber- culous tissue may be hastened, or the encapsulation of caseous areas effected. Are all cases of pulmonary tuberculosis suitable for the open-air treatment? Obviously not, for all cases are not susceptible of an arrest or improvement; and the object of this treatment is to cure. Although it is difficult, if not impossible, in many cases and in the various stages of the disease, to form a probable prognosis, still in general it may be said that advanced cases with mixed infection and septic symptoms — cases of very extensive disease, those in which the tuberculous process is accompanied by acute symp- toms and other complications, or those in which the recuperative power seems to be lacking, and the whole system appears to have collapsed — are unfavorable cases and unlit ted for the severe regime of the continu- ous open-air treatment. Fresh air, of course, should be afforded all cases, as to everybody else, sick or well; but this can often be best done in a well-venti- lated room, where the patient is made comfortable and kept at rest. If some of these apparently hope- less cases later exhibit more favorable symptoms and develop greater recuperative power, they then can more properly be subjected to the complete open-air treatment. I, est there may be some misunderstanding, it is well again to state what may seem self-evident, viz., that the open-air treatment in all its rigorousness means practically a continuous outdoor existence. Day after day in all kinds of weather one must be exposed to the open air, and the windows of his sleep- ing-room must be kept open day and night, summer and winter, or better, as is now so generally the custom, sleeping outdoors. This does not mean that one shall sit out in a rain or snow storm, but on a veranda for example, which affords shelter from the storm and wind and yet is open to the air. The writer, for ex- ample, had a patient at Rutland, Mass., who, during a New England winter, spent eight hours daily out of doors, always slept in a cool room, with open window .-. and bathed his chest every morning with cold water. As has been said above, a well-equipped sanatorium affords the best opportunity for taking the open-air treatment, and medical supervision is always at ham', to insist upon it; at the same time it is practicable, b very many cases, to devise at the home of the patient an arrangement lor this treatment. A properly pro- tected veranda, preferably facing the south; a tent with a wooden floor and properly ventilated; a shed or wooden chalet simply and cheaply constructed, serving also as a sleeping-room by night — all of these afford opportunities for the "treatment." If the physician is at all ingenious he will readily invent some way by which this can be accomplished, for there is almost always something in or about tin patient's house that can be utilized for this purpose, and the devices for securing open-air life are innumer- able; vide "Some Plans and Suggestions for Housing Consumptives"; "Fresh Air and How to Use It" (Carrington), published by the National Association for the Study and Prevention of Tuberculosis. It is hardly necessary to say that a patient used to an indoor life, as the great majority of them are, must be somewhat gradually accustomed to a constant open-air exposure, but it is marvellous how perfectly they establish the habit, and how complete is the endurance which they attain. Knopf 2 quotes Andvoid of Tonsaasen, Norway, as saying that he leaves hi patients on their chairs, wrapped in furs, for from live to nine hours a day at a temperature of-25° ('. (-13°F.). The number of hours during which the patient re- mains out of doors depends largely upon the location and latitude of the locality where he is. At Davos, for example, the sun rises late and sets early, on account of the surrounding mountains, so that a winter's day is only about four or five hours long. In Falkenstein the patients remain out of doors for from seven to ten hours a day all the year through; at Rutland, Mass., for about eight hours; at Colorado Springs for from seven to eight. The effects upon the patient of this prolonged stay in the open air are striking. Appetite and weigh! in- crease; cough and expectoration diminish; and if there is any rise of temperature at any part of the day, this is likely soon to disappear. The patient also experi- ences a sense of well-being and invigoration, together with mental exhilaration. After a course of open- air treatment one is no longer content to live indoors or sleep with closed windows. It may be pertinently asked if patients do not catch cold under this constant open-air exposure. On the contrary, experience has proved that they are less likely to do so than when they live under constanl protection with the consequent unavoidable exposure to impure air. The constant exposure to pure germ less air, however cold, when one is properly clad, does not render one susceptible to catching cold, as Nansen so strikingly proved on his Arctic expedition. In concluding this portion of the subject, it is well to reiterate that the open-air treatment is not the whole treatment of pulmonary tuberculosis. In addition, there must be an abundance of nutril and properly prepared food; rest; a most careful avoidance of over-exertion either mental or physical; moderate exercise under careful supervision, and in suitable cases; and due attention to the skin by the use of various hydrotherapeutic measures. In brief, all 140 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ar-in therapeutics tlic hygienic measures conducive to increasing the resistance of the individual to the infection, must be adopted. Surgical and Other Forms- of Tuberculosis. — Insti- gated by the success obtained in the open-air treat- ment of pulmonary tuberculosis, general and the orthopedic surgeons have been led to apply the same methods in the treatmenl of surgical tuberculosis, particularly that of the bones, joints, and glands in children and young persons, sometimes in conjunction with operative measures and sometimes without them, and the results have been as striking as with pulmon- ary tuberculosis. Prof. Halsted of the Johns Hopkins University go< s so far as to say that most of surgical tuberculosis will recover without ration if they are given a fair opportunity in the open air, 3 and lie further emphasizes the importance of d cures by the intensive employment of the out-of- door treatment by making it continuous, night and day, this being especially important with children affected with joint tuberculosis. It is a question whether seaside or country air is I favorable for such cases. Seaside sanatoria existed for a long time on the coast of France and England and other countries in Europe, and more recently a few have been established in this country, njotably "Sea-Breeze" at Coney Island; and excellent rtsults have been obtained. Likewise apparently gbod results have 1 n secured in the Adirondack^ and elsewhere inland. Probably it does not make very much difference provided the air is fresh and pure and a rigorous application of the open-air regime is enforced, i.e. the child being exposed continuously to the open air. At Leysin, Switzerland, which is some 4,000 feet above sea-level, the writer recently saw children in Rollier's Sanatorium suffering from various forms of surgical t uberculosis, especially of the bones and joints, treated by exposure of the naked body to the sun and open air; the deep color of their bodies, bronzed by the intense rays of the sun in the attenuated air of that altitude, made them look like North American Indians. The excellent general condition of these children, as evidenced by their well-nourished appear- ance, healthy complexion and exuberant spirits, and the rapid improvement of the local conditions, testified to the success and value of the treatment. Rollier attributes much of his success to the influence of the sun baths, but one must remember that the open air includes sunshine to a greater or lesser degree. The technique of the open-air treatment in surgical tuberculosis is essentially the same as that in the pul- monary form. It must, however, be absolute and continuous, for, as Halsted says, a rapidly growing boy, with tuberculosis of the knee joint, for example. might lose a great deal in the length of the affected limb unless the cure were rapidly effected. Tuberculous peritonitis is another form of the dis- ease peculiarly amenable to the open-air treatment, as are also tuberculous glands; and many cases recover under this treatment without surgical interference — indeed, in all cases of internal tuberculosis other than pulmonary, the open-air conditions of living are of great value even if they are not the determining factor in the cure or arrest. It is all important thai such accommodations shall be provided as will enable the patient to obtain fresh air continuously, be it again repeated, and this means sleeping out of doors at night as well as living out of doors during the day. Pneumonia and Other Infectious and Respiratory Diseases. — The provision of open-air conditions is now quite generally accepted by the profession as an essen- tial part of the hygienic care of pneumonia, and the more favorable results obtained attest the value of such procedure, as heroic as it at first seemed. Even with infants and young children the open-air treat- ment is fearlessly employed, and its value has been abundantly proved by Northrup, the pioneer in the use of outdoor air with children suffering from pneu- monia, and by many others. The patient i either placed directly on! of dooi i'l aii open porch or loggia, or in a lame room with wide open windows, i he bed being placed eith i bet een •. indov, or close to them, no mailer what the season of the year may 1"-. The e ential thing is to allow the pain at an unlimited supply of "free, fresh, (lowing i and the physician must determine in each individual case how this can be I be accomplished. Instead of the application of oxygen as a last resort the patient under the open-air treatment is obtaining a goodly supply of ii continuously and from the beginning. In winter the patient should, of course, be prop* protected, and when this is .lone, he will suffei BO di - comfort, whatever the temperature of the air, al- though the nurse will have to be clothed with thick winter garments. The effect of such constant ex- posure to outdoor air is better and more restful sleep, easier respiration, less cyanosis, and fe i nervous phenomena. In other acute infectious diseases an essential part of the hygienic management should always be a bountiful supply of pure, fresh, outdoor air, either in a large, well- vent dated room, in a well- vent dated tent , or an open porch. That was a wise old school physi- cian who said that if he had typhoid fever he wanted to be put under a tree with a jug of milk beside him. In acute bronchitis, especially in children, it is quite as important to supply an abundance of fresh air as in pneumonia, and essentially the same plan should be pursued in doing so as in the latter disea e. "Outdoor treatment (in acute bronchitis) should be a routine practice" says Musser. In chronic bronchitis and asthmatic conditions the open-air treatment can most comfortably be carried out in the warmer latitudes, such as in Southern California, the West Indies, Florida, the various re- sorts of the Southern Pine Belt, or on the Mediterran- ean coast of Italy, France, or Northern Africa. In many cases the open-air life can be properly insti- tuted for such conditions, occurring so frequently in the feeble and aged, only in climates milder and more equable than the cold and changeable one of the North in winter. Some cases of chronic bronchitis do best in a dry, warm climate and others in a warm, moist one. When for any reason the patient cannot change his climate in winter, he can often arrange an arti- ficial mild climate in his own house by confining him- self to a large room with a Southern exposure, pro- viding for free ventilation and a sufficient amount of moisture in the air. Thus he will obtain compara- tively fresh, warm, moist air, and a reasonable amount of sunshine. In the various chronic diseases of the upper respira- tory tract, such as pharyngitis, laryngitis, and rhinitis, the open-air treatment is again applicable; and often a change of climate where outdoor life is more easily obtained is desirable; and in choosing a resort the climatic characteristics must be taken into considera- tion in conjunction with the individual needs and local conditions. Convalescents from pleurisy with effusion will obtain a more rapid expansion of the compressed lung by the open-air treatment in high altitudes, provided the heart has recovered its former integrity and there are no extensive or firm adhesions. At all events, whether in a high or low altitude, pure, fresh air is most important in the after-treatment of pleurisy. Various Conditions of Malnutritions, Anemia, and Other Dyscrasias. — A residence in the mountains or at the sea-shore has long been recognized as perhaps the most important element in the successful treat- ment of malnutrition and anemia, particularly in children and young women. Although, probably, either the mountain or sea. air will produce more rapid results, yet any locality where pure, fresh air 141 Aerotherapeutics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES is obtainable will avail. Care must be taken, however, thai a really outdoor life is followed. "It is little use," says Trudeau, "merely to tell people to live out of doors, they must be made to do it, and suita- ble accommodations must be provided so they can do it." Depressed vitality, from whatever cause, conva- lescence from acute diseases and surgical operations, generally respond rapidly to the outdoor life in the country, mountains, or sea-shore. The beneficent effect of mountain air upon condi- tions of debility, anemia, and malnutrition are strikingly illustrated by a modest institution at Ste. Agathe, Canada, in the Laurentian Mountains, called " Brehmer Rest" or "Preventorium," where young women suffering from the conditions noted above, in- cident to life in the city, in shop or factory, conditions which are so often the forerunner of tuberculosis, are subjected to the open-air treatment for weeks or months, until the normal standard of health is re- st ured. Undoubtedly many cases of tuberculosis are thus prevented, and how much more satisfactory is this than a longer period in a sanatorium after the active disease has developed. Such an institution is rightly named a "Preventorium." The open-air school and the open-air school room have rapidly come into favor for anemic, illy-nour- ished school children, as well as those with latent tuberculosis. In such schools the children are practi- cally out of doors or in rooms with the windows wide open, throughout the year, well protected, of course, during the colder months. Instruction alternates with periods of rest, which is taken in the recumbent position. Nourishing food is also provided. Thus education goes on coincidentally with the open-air and hygienic treatment which is restoring the health to its normal standard. Organic Diseases. — In organic cardiac, vascular, or renal disease life is often prolonged and a more comfortable existence afforded by residence in such a climate as will permit of an outdoor life. A moderately warm, equable, sunny climate would appear to be that of choice. In renal disease sudden changes of temperature and wind are to be avoided. The debility and degenerative changes of old age are mitigated and produce less discomfort if one can live easily out of doors in an equable climate which makes the least possible demand upon the limited vitality. Such a climate as that of Southern Cali- fornia is ideal for the aged. In various functional nervous disorders, such as neurasthenia, insomnia, and neuralgia, much benefit is derived from exposure to pure, fresh, open air. Sometimes mountain air and sometimes that of the sea-shore will prove most beneficial. Each case must be judged by itself and that climate selected which seems best to satisfy the individual condi- tions. Thus it is seen that there is hardly any abnormal condition or disease that will not derive benefit from the open-air treatment, and in many diseases it will be the determining factor in the recovery. The supreme importance of fresh air breathed in the open is so obvious that it seems strange that it is so often ignored even by the physician. Modern civilization has so accustomed man to an indoor existence that outdoor life almost seems unnatural to him, and when he is ill, to be placed under open-air conditions appears to him and his friends as a danger- ous expedient. It often requires much reasoning and persuasion on the part of the physician to be allowed to institute the open-air treatment. The reader is referred to "Fresh Air and How to Use It," by Car- rington, published by the National Association for the Study and Prevention of Tuberculosis for an excellent detailed description of the various methods of applying the open-air treatment. Edward O. Otis. References. 1. Williams, C. Theodore: Aerotherapeutics, London, 1S94. 2. Knopf, S. A.: Prophylaxis and Treatment of Pulmonary Tuberculosis. :;. Transaction of the National Association for the Study and Prevention of Tuberculosis, 1906, p. I'M. 4. Northrup, W. P.: Cold Fresh Air in the Treatment of Pneu- monia in Infants and Children, Medical Record, Feb. IS, 1905. yEsculapius. — The Latinized name of 'AitkXtjiros the legendary Greek god of medicine, the son of Apollo and the nymph Coronis. Homer mentions him as a skilful physician, whose sons, Machaon and Podalirius. characterized by the poet as "blameless physicians," were sergeons "in the Greek camp before Troy. To Fit;. 52. — Statue of ^Esculapius in the I'ffizi Gallery in Florence; ii is said to be a copy of a statue by Myron, of the later Greek period. Homer ^Esculapius was still onlv a hero, a "cunning leech," but later he was deified by Greek tradition, lus worship being well established by the fifth century, B.C., at Athens. He carried his art to such a degree ol perfection as to be able even to raise the dead: thus Zeus, fearing he might abolish death altogether and depopulate Hades, slew him with a thunderbolt. The temples dedicated to ^Esculapius were always located in some conspicuously salubrious spot, out- side the limits of the town or city, as on the summit 142 REFERENCE HANDBOOK OF THE MEDICAL SCIENi Agar-agar of a mountain or in the midst of a sacred grove. Nobody was permitted to die on the consecrated land surrounding the temple, nor could any woman give birth in a child within these limits. Further] •<•, repeated purifications were required of all those who desired to approach the temple for the purpose of consulting the god. All who were healed offered sacrifice and hung up votive tablets, on which were recorded their names, their diseases ami the manner in which they had been cured. As these tablets were carefully preserved, the priests — the custodians of the temples —came, in the course of time, to have at hand a veritable library of reference, in which all the medical knowledge of that period was carefully stored, ready to be consulted on any convenient occasion. A.H.B. 1 villus — Buckeye; Horsechestnut (fam. Hippo- caatanacece). A genus of about a dozen species, of America and Asia, growing mostly north of the Equator. The bark and seeds of JE. hippocastanum 1... native of Asia, but largely cultivated for ornament in all temperate countries, have been much used in domestic practice in the treatment of malaria and rheumatism. Both contain considerable tannin, but the activity appears to reside in the bitter glucoside lin (0,,H,„O 9 +1.5PLO) which is crystalline, white, soluble in water and alcohol, and antiperiodic in fifteen-grain doses. The seeds of the red buckeye, M. pavia L., of the southern United States, are reported to have caused fatal cases of poisoning in children, the sj'mptoms being those of poisoning by saponin. It is even said that the former species has acted similarly. H. H. Rusbt. .'Ether.— See Ether. Aetius. — A Christian physician, born in Amida in Mesopotamia, who flourished in the early part of the sixth century. He studied at Alexandria and became ?ourt physician at Byzantium. He belonged to the sect of the methodists, yet inclined at times toward the practice of the empiricists. He wrote in Greek a treatise on medicine in sixteen books, for the most >art, and the most valuable part, a compilation from carious authors, chiefly Oribasius and Galen. His jwn contributions were those of a superficial observer ind obscure writer. The treatise, however, is on the ivhole a valuable commentary on the works of the Dlder writers, such as Galen, and furnishes a rich naterial for the history of the medical science of tntiquity. Eight books of the Greek original, edited Dy Comarus (q.v.) were printed at Venice in 1534, tnd a complete Latin translation, also by Comarus, >vas published at Basle in 1542. A. H. B. .•Etna Springs. — Napa County, California. Location. — At the upper end of Pape Valley, sixteen miles northeast of St. Helena. Access. — By rail via Southern Pacific Company's trains via Oakland and Vallejo Junction; or via the Napa Valley Route, steamer and electric cars to St. Helena, and thence by stage or automobile over a .veil-graded, picturesque road. There is no hotel tmilding, but a number of attractive cottages are provided for guests. Gardens, orchards, and vineyards supply fresh vegetables and fruits for the table. In the fall a season is given to the " Grape Cure." There is also i dairy. This resort, known as the "American Ems, "is delightfully situated at an elevation of 1,000 feet above the Pacific, in the midst of wild mountain sur- roundings. The mountains are well stocked with game, and the streams afford good fishing. Many forms of exercise and amusement are provided. There are a number of excellent springs in the neigh- borhood, those u ed for drinking purposes having a temperature ol 98 I : those employed for bathing show a temperature of 106° F. The following analy- sis of .Etna Spring was made by Professor \\ . T. Wenzell: Chains in ic.i (J. S. Wink GALLON, 231 CUBIC I Chloride of i ;;n no Nitrate <>t potassium.. u titm Silica f potassium . 0.780 Borosilicate "i pota - ium . 0, 150 I'., irate of sodium 19 Carl ate ol sodium 21.870 Chloride of sodium . . is. 550 Sulphate of sodium ... 0.020 < ' i rl lonate <>f calcium . . . 0. 750 Sulphate of calcium. - . 0.290 Carbonate of magnesi m, . 550 Carbonate of iron.. - 0.210 Oxide of iroD . 0.100 Amnion i:i . 006 Organic matter 140 Alumina 2.130 Total grains 96.760 Temperature. 72° F. Specific gravity (at 69°F.), 1.00317. Carbonic acid gas, 313 cubic inches. The following analysis of American Ems was made by Professor J. A. Bauer, chemist: Grains in One Wine Gallon of 231 Cubic Inches. I -rains. Bicarbonate of magnesium 13.85 Bicarbonate of sodium 75 . 22 Bicarbonate of calcium 10.45 Sulphate of sodium 7 . 73 Chloride of sodium 28 . 65 Silica 0.65 Total erains 136.55 Temperature, 9S° F. Caroonic acid gas, 58 cubic inches. The water is sparkling and invigorating, with a noticeable electrical element, and possesses a decided tonic influence as well as slight aperient properties. It is a good type of alkaline-saline-carbonate water and, as will be observed, resembles the waters of Ems to quite a marked extent. This water is in- creasing in favor on the Coast, and has already acquired considerable reputation in renal diseases. Good results have also been reported in cases of rheumatism, diabetes, and neuralgia as well as in those of dyspepsia, torpidity of the bowels, hepatic disorders, skin affections, and uterine disease. Several other springs are found close by. Besides those above mentioned are the Iron Spring, much resorted to for anemia and wasting affections, the Bath House or Artesian Spring, the Soda Spring, and the Iadora Spring containing soda, magnesia, and iron. Emma E. Walker. Agamofilaria. — A name given to certain immature parasitic nematode worms, the adult stages of which are unknown, bvit which belong to the family Filari- idoe. See Nematoda. A. S. P. Agamodistomum. — A name given to certain imma- ture distomes which are sometimes parasitic in the human eye. See Trematoda. A. S. P. Agar=agar. — Vegetable gelatin. The name of a large number of East Indian sea weeds which are used in the manufacture of "vegetable gelatin"; also the name of this gelatin. The general nature of these substances is similar to that of chondrus, or Irish moss. It is one of these species which yields the material for the Chinese "bird's-nest pudding." Agar-agar is 143 Agar-agar REFERENCE HANDBOOK OF THE MEDICAL SCIENCES manufactured chiefly in China, the sea weeds being sent there from other conn! ries for this purpose. It is, however, more or less manufactured in other count ries also, especially in Japan, and it is the latter variety which is chiefly used for bacterial cultures. In the country of its production, agar-agar is very largely used for food, both alone and as an ingredient of jellies. It is also very largely employed as a sizing in silk manufacturing. It occurs in thin, transparent, colorless sheets, a great many bound together, or as bundles of long shreds, or in the form of irregularly square sticks, nearly a foot long. The latter form is that generally used in bacterial work. It is less transparent than either of the others, and is not so white. Agar-agar consists almost wholly of gelose, a sub- stance the solution of which cools to a jelly, which is much more stable than that of gelatin, requiring a higher temperature for melting. It is said that a solution of 1:500 of water will yield a stiff jelly. Gelose is precipitated by alcohol, but not by tannin. Gelasine is merely a variety of agar-agar. Agar-agar has no medicinal properties, its uses being wholly nutritive and mechanical. Its paste is some- times used as an ointment base. Recently it lias been employed in the treatment of constipation. It is ad- ministered for this purpose in dry form in the food; ab- sorbing water in the intestine it forms a jelly mass which increases the bulk of the feces. This mechanical action is sometimes supplemented by the addition of a laxative, as e.g. cascara sagrada in the preparation known as regulin. H. H. Rusby. Agaric, Purging. — While agaric; Touchwood; Spunk; Timler. The decorticated hymenium of Polyporus officinalis Fries (Boletus laricis Linn.; order, Basidio- mycetes, Hymenomycetes). This is a large fungus growing upon the stems of the European larch and of one or two other conifers. It forms large hoof- shaped masses upon the sides of the trunks, and pene- trates with its mycelium deep into the wood. When young, these bodies are soft and juicy, but when fully grown, hard and of a consistence between spongy and corky. Agaric is collected in Europe, Asia Minor, etc., and usually prepared by drying and peeling. It is in yellowish-white, friable, light, and spongy irregular balls and lumps, from the size of an orange to that of a coconut and larger. It has evidently been peeled, and the surface is finely rough and dusty with minute separated particles. The texture is rather firm, but soft; it can easily be reduced to a coarsish powder by friction or by rubbing on a sieve, but is difficult to pulverize finely; its microscopic structure — a tissue made up of interlacing, thread- like cells — explains its peculiar consistence. Agaric has a heavy fungous odor, and a slowly de- veloping, bitter, nauseous taste, which is at first sweetish. Its powder is very irritating to the eyes and nose, and produces violent sneezing. As it is also light and dusty, persons employed in beating it in mortars are obliged to resort to devices to prevent its rising. It contains nearly one-third of its weight of resinous matters, extractible by strong alcohol, and these can be separated further into three or four simple resins. The active principle is agaric or agaricic acid. Com- mercial agaricin is a concentrated extract of agaric, and constitutes an impure and indefinite mixture of the resins, but the Agaricin of the German Phar- macopoeia is agaric acid. Agaric, as its name indicates, was originally used chiefly as a cathartic, but such use is rare at present. 1 1 i-. now rather considered that purgation is indicative of over-dosing. It is, in fact, but little employed in its own form, while agaricin and agaricic acid are growing in favor as remedies for the control of sweating, especially in phthisis. The dose of agaric is 0.02 to 0.06 gram (grain iij. to x.). More than this acts as a purgative. (See also Agaricic Acid.) H. H. Rusby. Agaricic (or Agaricinic) Acid. — (CV.H^Os + H.,0.) The active constituent of agaricin. It occurs as a white, almost tasteless powder, soluble in alcohol and with some difficulty in water, and may be given in doses of 0.02-0.03 gram (grain £ to A), for the s: • purposes as those for which agaricin is used. (See Agaric.) H. H. Rusby. Agathin. — Cosmin-salicyl-alpha-methyl-phenyl-hjr. drazone, C 6 H s CH 3 N,.CH.CH 4 OH. This compound results from the reaction between the basic alpha- methyl-phenylhydrazin and salicylic aldehyde. It occurs in colorless crystals, or in greenish-white crystalline flakes; is odorless, tasteless, insoluble in water, and soluble in alcohol and ether. It was introduced by Roos as a remedy for rheumatism, and has been found effective in this disease and in neuralgia. It has been known at times to produce headache, but the claim is made that it neither depresses the heart, nor gives the general symptoms of salicylism. Dose: gr. iij. to x. (0.2-0.6) from three to six times a day. W. A. Bastedo. Age. — (Lat. cetas). The age of a person is usually reckoned as the period which has elapsed since his birth. This method, although the most convenient, does not represent the true length of life. The new organism is formed by the union of an ovum and a spermatozoon, and the individual life really begins at the time of that union. (See Impregnation.) Practically, it is best to divide the span of life into two main epochs: (1) antenatal, and (2) postnatal, Age during the first epoch is reckoned from the time of fertilization (conception), and, during the second, from the date of birth. There are three principal ways of expressing age. The usual method is in terms of time (chronological age). Age may also be expressed in terms of develop- ment (anatomical age), or in terms of functional activity (physiological age). Variability is a fundamental property of lhing things, and is manifested at all times of life. This is as true for the rates of developments as for other characteristics, and, for this reason, the chronological age does not correspond exactly to the anatomical or to the physiological age. Ages expressed in these three ways are correlated, but the correlation is not so close as is usually supposed. (See Variation.) The antenatal epoch may be divided into two periods: first, the embryonic period; second, the fetal period. The first lasts from fertilization until the organs are clearly formed, about sixty days; the second, or time of intrauterine growth, from the end of the embryonic stage until birth at about the two hundred and seventy-first day. The postnatal epoch is divided in various ways by different authorities (Chamberlain, 1900). The scheme given below is modified from the scheme of Tigerstedt (1906), and has eight periods. (1) The new-born baby, tilt the falling of the umbilical cord on the fourth or fifth day. (2) Early infancy, to the seventh or ninth month when the first teeth erupt. (3) Later infancy, lasting to the appearance of the first permanent teeth at about the seventh year. (4) Childhood, from permanent dentition to the onsel of puberty at about the thirteenth or fourteenth year. (5) Adolescence, till the full stature is attained al about the twenty-first year. (6) Maturity, the period of complete functional activity, ending at about the forty-fifth year with the decline of the sexual function (7) Middle Life, extending to the waning of the phys- 144 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Akp i ca ] and mental functions thai indicates the gradual ition to old age. (8) Senescence, marked by ,uii, 1 degenerative changes which finally end in death. Estimation of the Age of Fetuses.- The duration of pregnancy is reckoned usually fr the first day of the menstrual period, but in order to determine the irobablc age of the fetus, it is necessary to make certain deductions. These will depend on which part if the menstrual cycle furnishes the most favorable :onditions for fertilization. The menstrual cycle normally occupies twenty- it days, and is divided into four periods. These ire — (1). the intermenstrual time, a period of about fourteen days, during which there is very little hange in tin- mucous membrane of the uterus; he premenstrual period of six or seven days, a lime of proliferation and thickening of the mucous membrane; i:l) the menstrual period, three to five lavs, with extensive degeneration of the mucous membrane resulting in a decrease of thickness; and ue postmenstrual period, during which time the mucous membrane is regenerated. ( >v ulation, apparently, may occur at an} - time during this cycle, but, according to the Reichert-His theory, the generally accepted theory, the most fre- quent time of ovulation is toward the close of the premenstrual period, and if fertilization takes place immediately the menstrual period which would v is inhibited. Therefore, the probable age of the fetus is obtained by subtracting twenty-eight lays from the time since the beginning of the last menstrual period. Mall (1910), on the other hand. concludes, from data collected by Leuchart, that, when copulation occurs late in the menstrual cycle, the spermatozoa may reach the surface of the ovary, and there await the appearance of the ovum, and that, if fertilization follows in the premenstrual period, it does inhibit menstruation. If copulation occurs after istruation, the spermatozoa may meet the ovum and fertilize it on its way down the tube. He regards the latter as the most probab e event, because in 1,200 cases, it was found that the duration of preg- nancy was ten days longer on the average when reckoned from the first day of the last period, than ■ hen reckoned from the fruitful copulation. Most pregnancies begin during the first week after menstru- ation. If the fruitful copulation has occurred late in the menstrual cycle, the apparent duration of preg- nancy, as calculated from the last menstrual period, is longer than when copulation has taken place earlier in the cycle. From a large number of records of duration of pregnancy, reckoned from the beginning of the last menstrual period, Mall concludes that the mean age of a child at birth is 271 days. Its average length is fifty centimeters. Thus, when the menstrual history is known, the age of the fetus can be estimated by taking the time elapsed since the beginning of the last menstrual period, and correcting this for the probable time of conception. When, however, the menstrual history - is unknown, recourse must be had to tables showing the rate of growth of the fetus. Three standard measurements are used to express the size of a fetus. These are the crown-rump, or sitting height, the crown-heel, or standing height, and third, the neck-breech, ehiefly useful for embryos from four to seven weeks old. This last measurement has been made in various ways. Mall i 1910) recommends that the upper point of this line be taken where a line drawn through the middle of the lens and the auditory meatus, the oculoauricular line, intersects the dorsal surface in the median plane of the body. Graphic tables (Mall, 1910, Figs. 115 and 146) appear to show- a close correlation between the crown-rump height and the crown-heel and neck-breech measurements respectively. Just how • the relation is, however, it is not possible to say, Vol. I.— 10 for the coefficients of correlation have not been cal- culated and ii i ei afe to rely on graphic method alone lor statistical deductions. (See Variai While these three measurements would appear io be practically interchangeable, Mall regards the crown-rump measurement a- the best standard for the present, and next to it the crown-heel. Having obtained an exact measurement of the fetus, the age can be estimated by comparison with a table made from data concerning embryos and fetuses of known menstrual history, showing the relation between size and age. Mall (1910, p. 199 and I ig 1 17 and 1 Is) gives such a table. It is assumed that fertilization most frequently occurs ten days after the beginning of the last menstrual period. With this assumption, the table gives, for each week of antenatal life, tin- mean menstrual age, the mean crown-heel and the- mean crown-rump measurements in millimeters, as well as other data useful for esti- mating age. This is reproduced in part in Table 1. Table I. — For Estimating: Act. of Ff.tcses. Mull, 1910). Probable age in days. Mean menstrual age. Mean length of the embryo, crown-heel. mm. Mean length of the embryo, crow n-rump. mm. 7 1 1 21 31 .5 .5 28 37 2.5 2.5 35 43 5.5 5.5 42 :i 11 11 49 59 19 17 56 65 30 25 63 72 41 32 70 79 57 43 77 S6 76 53 si 94 98 68 91 100 117 81 98 108 115 100 1115 111 161 111 112 121 180 121 119 128 198 134 126 136 215 145 133 113 233 157 110 150 250 167 117 157 268 180 154 165 2S6 192 161 171 302 202 16S 177 315 210 175 185 331 220 182 192 345 230 189 199 358 237 196 205 371 245 203 212 384 252 210 219 400 265 217 228 115 276 224 234 125 2S4 231 241 436 293 238 24S 44S 301 215 256 460 310 252 262 470 316 259 271 4S4 325 266 276 494 332 270 2S0 500 336 The New-born Baby. — This critical period of life lasts from birth until the umbilical cord shrivels and falls off, usually about four or five days. At the beginning of the period there is a sudden change in the methods of respiration and nutrition. The supply of oxygen and food from the maternal blood is cut off, the first air is inhaled into the lungs, and the first food taken into the stomach. The accumulation of carbon dioxide stimulates the res- piratory centers to their first effort, and, when once begun," respiration is rapid, about 35 per minute. The filling of the lungs causes a profound change in the circulation. Blood, which before that event had passed from the pulmonary artery directly through 145 Age REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the ductus arteriosus into the aorta, is now directed into the right and left branches leading to the lungs, and returned to the left side of the heart through the pulmonary veins. The ductus arteriosus begins to contract immediately upon the establishment of pulmonary respiration; and partly by this means, and partly by a thickening of its walls, becomes closed by the sixth or seventh day. The changes in the fetal circulation do not take place all at the same time. The first to be completed is the closure of the distal ends of the allantoic, or umbilical, arteries; and the last is the closure of the foramen ovale of the heart, which may remain incomplete for months. The movements of the child during this period are largely of the random type. There are few estab- lished reflexes during the first week, but Darwin found that sneezing, hiccoughing, yawning, stretching, sucking, and screaming were well performed during the first seven days. (Hobhouse, 1901, p. 40.) The sucking movements are reflex rather than instinc- tive, and, at first, are often made at random, the baby frequently sucking at the wrong place (Hobhouse, p. 42). The senses at this time appear to be defective. The new-born child is said to be wanting in a true olfactory sense, and its eyes are oversensitive to light, and probably do not form clear images (Cham- berlain, pp. 77-79) That the changes in mode of existence incidental to birth produce a crisis in the life of the child, and present new conditions to which the child adapts itself with difficulty, is shown by the loss of weight which normally occurs during the first few days, and by the high rate of mortality. Earliest infancy, as well as other periods of human life, has its charac- teristic diseases, but, 'unfortunately, statistics of morbidity are lacking, and the relative frequency of diseases can only be judged by means of the statis- tics of death. The Mortality Statistics, 1910, pub- lished by the U. S. Bureau of the Census ( Bulletin 109) , show for the first time in the United States the mor- tality due to each of the principal causes of death during each of the first six days of postnatal life. For the year 1910 there were reported 36,351 deaths of infants less than a week old. Of these 16,197 died as a result of premature birth, and more than half of these deaths occurred on the first day. The next most important cause of death was congenital debility, of which 5,943 cases occurred in the first week, and 2,007 during the first day. Malformation comes next, with 1,437 deaths during the first day, and a total for the first week of 4,380. Convul- sions and syphilis complete the list of important causes of death of the new-born. Here we see natural selection rigorously at work weeding out the unfit as soon as they leave the protection of the mother's womb. Early Infancy. — Having survived the dangers of birth, the infant resumes its growth, and during the next few months undergoes a growth more rapid in proportion to size than at any other period of post- natal life. In fact, after this early maximum, the relative rate of growth gradually diminishes, except for a considerable rise at the time of puberty, until the complete stature is attained in about the twen- tieth year (see Growth). The skeletion is still carti- laginous to a considerable extent. Recent studies on the development of the wrist bones by Pryor (1906, 190S) and by Rotch (1909) have shown that the epiphyses are usually wholly cartilaginous, and the carpal bones do not exhibit any centers of ossi- fication in the early part of this period. The move- ments now change from random and reflex to more adaptive and complicated instinctive actions. Bo- manes (1892) has pointed out that some of these are remarkably simian in character; for example, the position of the feet and great toe, and the grasping iniivement coupled with extraordinary development of strength in the hands. The child has a marked tendency to grasp any object, especially hair, which comes into contact with the hands, and, at three weeks of age, can, by holding on to a horizontal bar, support its own weight for a half to more than two minutes. The sense organs soon become completely functional, and the eyes show the maximum power of accommodation. The face changes from stupid passivity to an animated expression, and the cries change from disordered sounds to expressions of emo- tion and desires intermingled with laughter and tears. Although this development of the baby brings with it a rapid decrease in the chances of death, this period of early infancy has its grave dangers. During the first month, congenital debility and premature birth are still important causes of death. Cases of diarrhea and enteritis and of bronchopneumonia appear with rapidly increasing frequency, and, during the greater part of the period, become the most important causes of death. The maximum number of deaths from bronchopneumonia and pneumonia occur during the second half of the first month. Diarrhea becomes the most dangerous disease in the second month, and continues as such until the end of the period, reaching its maximum in the fourth month. Later Infancy. — This period begins with the eruption of the first tooth and ends at the first appear- ance of the permanent dentition with the eruption of the first true molar. It extends from the sixth month to the sixth year. The usual ages at which the teeth of the temporary dentition appear, according to Legros and Magitot, are as follows (Hill, 1909, p. 138): First inferior incisors Sixth month. First superior incisors Tenth month. Second inferior incisors Sixteenth month. Second superior incisors Twentieth month. First inferior premolars Twenty-fourth month. First superior premolars Twenty-sixth month. Second inferior premolars Twenty-eighth month. Second superior premolars Thirtieth month. Canines Thirtieth to thirty-second month The replacement of the cartilaginous skeleton by bone is incomplete at birth, and makes important advance during the period of later infancy. Pryot has studied the development of the bones of the hand and wrist by the or-ray method. Rotch (1909), using the same method, has confirmed Pryor's results con- cerning the wrist bones, and proposes to use the stages in their development as indices of anatomical age. From a study of 289 children, Pryor (190S) has constructed the following table showing the varia- tions in the order of appearance of the carpal boms, doubtful cases being omitted. Table II. — Order of Ossification of Carpal Boxes. o a c to S3 PS a u ,C a P g 'S a 3 O ci a 1 m 'o -c a ej a CO -6 'o N ft) a S a ,3 '5 o Q. i '5 1 23S 5 9 5 236 219 12 i 10 176 3 8 7 - 8 SO 36 30 6 2 27 59 31 - 6 l'.l 21 51 8 Totals 243 2-11 229 204 129 12 1 119 i u; REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arc Rotch (1909) finds that the Lower epiphysis of the adius begins to ossify soon after the unciform, and the ower epiphysis of the ulna appears after all the ither carpal' bones except the pisiform. Counting hese two epiphyses in with the eight carpal ossifi- cations, we may modify a table given by Rotch J. c, p. IS) as follows. Tadle III. — Staoes of Anatomical Age as Indicated by the Ossifications in the Wrists. Stage. Number of centers. Approximate age in years. A 2 &— 1 B 3 (?— 2 C 4 6*— 31 D 5 9— 3i d 1 — 41 E 6 9 — 11 0^-51 F 7 1 d 1 — 53 G 8 9 — 51 6 1 — 63 H-J 9 9— 62 c*— 71 to K-.U 10 9—101- d"— 12J- The data in regard to six and chronological age in this table are taken by Rotch from observations made by Pryor. Rotch (1909) gives the record of his own observa- tion on 133 children showing sex, weight, height, num- of teeth, development of the wrist, mental con- dition, and approximate age in years. These children were selected as being normally developed. Besides being of an average height and weight and healthy looking, they were known to have had no disease that could cause an enlargement of the carpal bones and epiphyses, and they had not shown any con- dition that would tend to retard the normal devel- opment. From his results Table IV has been com- piled. This shows the relation between chrono- logical age, sex, number of teeth, and number of ossi- fications in the wrist. The columns in this table are divided into squares, each square is subdivided into two sections, and a diagonal line crosses each section. The "argument" is the chronological age, and the tabular entries are the numbers of individuals having the numbers of teeth or wrist bones indicated at the heads of the columns. The numbers in the upper section of each square refer to teeth, in the lower section, to wrist bones. In each section, the number on the left of the diagonal indicates males; on the right, females. These observations, although too few for statis- tical analysis, indicate that the development of the temporary dentition is relatively rapid, being com- pleted by the end of the second year with little show of variation. The development of the wrist bones is a more gradual process, and is very variable in respect to chronological age. But by the time the first molars of the permanent dentition have erupted, the majority of children show at least eight ossi- fications in the wrist, the complete number except for the epiphysis of the ulna and the pisiform. In some cases the epiphysis, too, has appeared. As Crampton (1908 0) has said, the question of the value of Rotch's criterion of anatomical age can be settled only by establishing a correlation between the stages of development of tile wrist and the progress of other organs or functions. The material for such a correlation is, however, not yet available. Two events that especially distinguish man from the lower animals occur during this period. These are the acquirement of speech, and the assumption of the upright position. The change from inarticulate cries to the formation of words is a gradual one. At the beginning of this period, the infant lias learned to make dental articulations, and its babbling takes the form of syllables such as da, I", "'". and toward the end of the first year, or at the beginning of the second, the first words are spoken, mamma, /'»/'«, to which some more or less vague meaning is attached. This is tin' commencement of the imitative period, when the child attends to the words it hears, and tries to reproduce them. The preparation for walking is largely concerned with the growing strength in the legs and arms of the child. Attention lias already been called to the relatively great strength of hands and arms of a new-born baby. _ With the rapid accumulation of fat, however, the infant soon becomes, too heavy to support its own weight, and can only wave its arms and legs. As the muscles become stronger and larger, the ability to support the weight gradually returns. The child can sit up, then it can creep, and soon it learns to pull itself to a standing position beside a chair. Then it takes the first tottering steps, and finally, in the third or fourth year, it begins to walk easily. At the beginning of this period, there is a gradual diminution in the mortality from the infections of the endodermal organs — the digestive tract and the re- spiratory aparatus. Whether this is due to natural selection or to a gradual acquirement of immunity, it is impossible to say. Diarrhea, while diminishing considerably, still remains the chief cause of death to the end of the second year. It has active com- petitors in diphtheria and croup which, grouped together, reach their maximum frequency in the second year, and, with scarlet fever as a second, are left the chief causes of death in the fourth and fifth years. Childhood. — This period starts when the eruption of the first true molars has taken place and ends with the onset of puberty. Permanent dentition, with the exception of the third molars or "wisdom" teeth, which come later, is established during these years. The times at which these permanent teeth appear as determined by Legros and Magitot are given in the second column of Table V. The columns to the right give the sex. age, and variability as tabulated by Crampton chiefly from data collected by Boas. At the beginning of this period, the wrist bones are in Rotch's stages, G or H; at the close of the period, they have probably reached stage M. At stage K the first appearance of the pisiform is noted. The other stages after H still need more exact definition to make them available for statistical treatment. Hall (190-1, p. 9) says of this age: "The years from about eight to twelve constitute a unique period of human life. The acute stage of teething is passing, the brain has acquired nearly its adult size and weight, health is almost at its best, activity is greater and more varied than ever before or than it ever will be again, and there is peculiar endurance, vitality.and resistance to fatigue. The child develops a life of its own outside the home circle and its natural interests are never so independent of adult influences. Perception is very acute, and there is a great immunity to expo- sure, danger, accident, as well as to temptation. Reason, true morality, religion, sympathy, love, and esthetic enjoyment are but very slightly developed. Everything, in short, suggests the culmination of one 147 Age REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Table IV. — Number of Teeth and Wrist Bones in Relation to Age and Sex. Teeth. Wrist. 1-2 A- 2. 3-4 B = 3. 5-b C-4. 7-8 D=5. 9-12 E = 6. 13 -IS F=7. 17-20 G=8. 24 H-J = 9 25 K-M = 10 ►.& 1— G months 5 ^*^ J>^ 1 5 ,'' 7-11 months- 3 .^ 1 ^^ ^-^ 1 1 -^ 1 i^^ ^-^ 1 1-2 years 2 ^*^ ^^ 1 1 ,^ _^^ 1 ^^^ *^^ 3 ,''' ,-' 1 ,''' 1 1 ,-'' 1 2-3 years. 4 ^-^^ ^-^ 4 >> ,-*' 1 3 ,-' ,-'' 1 1 ,''' 2 C e3 c _ 3-4 years. ":f —---.' ^'^" 2 ,-'"' 1 1 "'' „,-'' 1 .,-"' 1 4 -^ _______?, ,-''' 1 J 4-5 years 5 ^-^ ^-^ 5 ,-''' 1 1 ,--' ,-' 3 2 -^ ,.--"' 1 1 ,-' 1 ^,'- 5-6 years. ________ ,--' 1 ______ .______. ,""'' 2 ,-'' 2 ,-'' 1 6 -7 years 1 ,-'' ,-'' 1 ^^ 3 ^^4 -'""' 3 >--'' S 7—8 years. 1 ^-^ 7 ^^ s^ 2 o 2 ,-' 4 ,--' 8-9 years. 4 ^^ 4 ,--'"" 9 -10 years. >-^ 5 ^^ o 2 5 ^""' --'' 3 1 .-'l -'' 1 10 -11 years. /^ Z 5 5 --'' .--' 1 ,-'' 2 11— 12 years. 4 ^^ ^"^ 5 1 >"\ 12-13 years. 4 -^"'' ^^ 4 s' 1 4 ,--'' --''' 5 Table V. — Age of Eruption op Permanent Teeth. Teeth. Age. Sex. Mean age. o-6 years 6-7 years 8 J years 0-10 years 10-11 years 11—12 years 12-13 years 1 8-25 years Second incisors First premolars Second premolars .... [% it? 7.0 7.5 8.9 9.5 9.0 9.8 1 .6 years 1 . 4 years 2. 1 years 2 . 1 years 2. S years 1 . 6 years 1 6 it? (_, I t? 5 1 t? 11.2 11.3 12.8 13.2 19.3 22.0 1 .4 years Second molars ...... Third molars 1 .0 years 1 . 6 years 2 . years 2 . 1 years 1 . 8 years The Greek letter aigma (") j s the symbol for the standard devia- tions, a measure of variability (see Variation), 1 IS stage of life. As if this represented what was once and for a very protracted and relatively stationary period, the age of maturity in some remote, perhaps pigmoid, stage of human evolution, when, in a warm climate, the young of our species once shifted for themselves independently of further parental aid." The relative immunity from disease at this age is shown by the mortality statistics. Of 805,412 deaths reported in 1910 (IT. S. Census Bulletin 109), 17,943 were of children aged five to nine years, and only 11,736 at the ages of ten to fourteen. During the first five years, the most frequent cause of deatn wns diphtheria (2,938); scarlet fever was second (1,731); tuberculosis of all kinds, third (1,422); and pneumonia, fourth (1,138). In the second five years, tuberculosis becomes the chief cause of death (all kinds, 1,634); typhoid fever, second (8 appendicitis, third (718); and diphtheria, fourth (709). Adolescence. — The period from the onset of puberty EEFERENCE HANDBOOK OF THE MEDICAL SCIENCES A ci- lo the attainment of maturity is called adolescence, . 1M ,I the corresponding age in years is generally con- sidered to be from twelve to twenty-one for girls and from fourteen to twenty-five for boys. (Cramp- ton (190S 6) defines puberty as the moment when the sexual life begins. In girls, this time is plainly indicated bv the first menstruation; in boys it is not so easily determined, but i.s indicated by the appear- of'the secondary sexual characters. These are: first, the growth and pigmentation of the hair upon .- MO .... ' ,0.1 HO no ii 3'.' 347 »i« II 100 irj 102 / ft] I? 1 1 i nrvo of Frequency of 3,500 Cases of First Menstruation (observed by Heinricius in Finland) . the pubic eminence and in the axilla? in both sexes; id, the development of the beard and change -ire in boys; and, third, the development of the ts in girl's, and the deposition of subcutaneous giving the pleasing rounded contours so charac- teristic of young womanhood. The chronological age of the first menstruation differs in various countries and in the individuals of each country. From the numerous collections of statistics quoted by Hall (1904, p. 474-8), it would appear that the average age in southern Asia is be- tween twelve and thirteen; in southern Europe. thirteen and a half to fourteen and a half; central Europe, fourteen to fifteen; and northern Europe, between sixteen and seventeen. In the United Mates, a number of investigators have found an average age of about 13.6; others place the age a i 1 1.5. While the average age does not necessarily coincide with the age of greatest frequency, they may lie Dearly the same. This is shown by 3,500 recorded cases collected by Heinricius (1SS3) in Finland. His results are given in Table VI. Table VI. Age, years. v. ol cases. 11 1J 13 14; 15 16 17 18 10 20 212:2 933 135 440 765 S46 560 347 198 102 11 12 L 2:; 2:, 21; 4 1 The average age is 15.82, and the tabular age of atest frequency i.s sixteen, and when the curve of variation is plotted (Fig. 53), it is seen to be a slightly ^kew curve. (See Variation.) A similar curve is given bv the statistics of 3,000 Prussian girls, collected by bullies (1886) and quoted by Hall (1904, p. 475). Marro (1901) has collected the statistics of the signs of puberty in girls, including not only menstruation, but also the appearance of pubic hairs, of axillary hairs, and the development of the breasts. These results have been presented by Crampton (190S 6) in a table reproduced below, which, for each year between the ages of nine and a half and eighteen and a half shows the percentage of girls that exhibit each of thesefour signs of puberty. The lineal the IhiII.hu of the table has been added to show the relative fre- quency of first menstruation at each ■<■ ! AGE 9.5 10.5 11.5 12.5 13.5 14.5 15.5 KS.5 i i .5 18.5 /fy ' -^-* ^-** 00 ty // /// / -// o 00 < 1- 2 50 en w in I i i h f fi (4 J^' AXILLA MENST.- ■ BREASTS^- K- Fio. 54. — Integral Curves showing the Percentage of Italian (Jirls who at Each Age had Attained Each of the Four Signs of Puberty. (From statistics by Marro.) Table VII. — Percenta IE OF Italian' Puberty. jIRLP Showing St ;\-. OF Age in years. . . 9.5 10.5 11.5 12.5 13.5 14.5 1 ', . 5 16.5 17.5 IS. 5 Pubes, '. 3 3 9 35 57 76 S9 100 Axilla, % ... 3 3 6 16 12 64 74 90 or, Menstr'ation % 3 3 3 15 55 67 77 96 100 Breasts, f "; 3 3 7 13 to 71 82 96 96 First .Menses. . . 3 12 10 12 10 19 4 The curves plotted in Fig. 54 show the same facts in graphic form. From examination of the table and curves, it will be seen that half of the girls had menstruated before the end of the first half of the fifteenth year. The pubic pubescence appeared somewhat earlier, while the axillary pubescence and the breasts developed at about the time of the first menstruation, sometimes a little earlier, some- times a little later. A similar table from the same sources and the curves (Fig. 55) plotted from it, show that in a group of Italian boys studied by Marro, pubic pubescence had appeared in fifty per cent, by the end of the first half of the sixteenth year. The axillary pubes- cence becomes evident nearly two years later, and a year later still the mustache begins to grow. Table VIII. — Percentage of Italian Bots Pi-bescent at Various Ages. 12.5 13.5 14.5 15. i 5. 16.5 17.5 18.5 14 29 59 77 100 100 11 9 33 57 88 1 29 43 60 149 Age REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Crampton lays great stress on the pubic pubescence as an indication of physiological age. He defines pubescence as the process of becoming covered with hairs, especially the pubic pubescence. A pubes- cent is an individual undergoing this process, which presents three phases. The first is the appearance of an evident and rapid growth of fine hairs upon the [00 o BO 80 70 60 £50 o UL Ld a. 40 30 20 10 12.5 13.5 14.5 AGE 15.5 16.5 17.5 18.5 19.5 / / / j / / 1 1 1 1 1 1 1 / i 1 / I i i i ■ 1 1 ; / / / / S ^ AXILLA Fig. 55. — Plotted from data given in Table VIII. (After Cramptou.) pubic eminence, the second is the pigmentation of this hair, and the third is the acquirement of its characteristic twist or kink. A prepubescent is an individual in whom this process has not become evident; a postpubescent is one who by reaching the third phase, has completed the process. From an examination of 3,835 high school boys in New York City, Crampton obtained the data presented in Table IX. ossification of the epiphyses which is completed with the cessation of growth at the end of this period. In regard to the mental condition of the adolescent Hall says: "Adolescence is a new birth, for the higher and more completely human traits are now born The functions of every sense undergo reconstruction; and their relations to other psychic functions change The voice changes, vascular irritability, blushing, and flushing, ,„ ^" 1 /"' -^ ~3? -o ,Z Z . / / / / A / / / / I / j ™ / 1 ~7^r ' ,/ jf" s '" 12.25 12.75 13.20 13.75 11.25 11.75 15.25 15.76 16.25 1G.75 17.25 17.75 AGE; HALF YEAR MEAN Fig. 56. — Integral Curves showing at each age the percentage of New York High School Boys in each of the three phases of Pubescence. Plotted from Table IX. are increased. Sex asserts its mastery in field after field. There are new repulsions felt toward home and school, and truancy and runaways abound. The social instincts undergo sudden unfoldment, and a new life of love awakens. It is the age of sentiment and of religion, of rapid fluctuation of mood, and the world seems strange and new. Interest in adult life and in vocations develops. Youth awakes to a new world, and understands neither it nor himself." The death rate during adolescence is still low, but considerably greater than during childhood. Of a total of 805,412 deaths reported in the registration area of the United States during 1910, 19,772 occur- red between the ages of fifteen and nineteen years. Table IX. — Age of Pubescence in High School Boys of New York City (3,835 Cases). Age, half-year mean. 12.25 12.75 13.25 13.75 14.25 14.75 15.25 15.75 16.25 16.75 17.25 17.75 Prepubescent (81)* 69 55 11 26 16 9 5 2 1 (16)* 25 26 2S 28 24 20 10 4 4 2 (21* 6 IS 31 46 60 70 So 93 95 98 100 * Calculated. This table, represented graphically in Fig. 4, shows that, in this group of boys, fifty per cent, have entered the first phase of pubescence by the middle of the fourteenth year and have completed the process before the middle of the fifteenth. The rate of growth, which has been gradually decreasing during childhood, increases during pubes- cence, and, according to Crampton, reaches a climax at or immediately after the change to postpubescence. (See Groivth.) There is an acceleration in weight and strength at the same time. Among changes in the internal organs in puberty may be noted an in- crease in the size of the heart and in lung capacity, a loss of fat in boys, and a temporary loss in girls, a lengthening of the jaw, and an acceleration of I Ik- ISO Tuberculosis of the lungs was the chief cause with 5,166 cases. In the next five years, the number nearly doubled; 9,622 cases. Typhoid fever was next in importance, and was likewise increasing, there being 1,681 cases in the years fifteen to i teen and 2,067 in the years twenty to twenty-five. Organic disease of the heart, and pneumonia, about equally important, and both increasing, occupy the third place. Maturity. — No sharp line can be drawn between adolescence and maturity. Between the twentieth and the twenty-fifth year the fully adult stature is attained and growth ceases. The change is so grad- ual as to be hardly perceptible. Now both psy- chic and physical functions have reached their max- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Agenesis iiiHiia development and power. According to Osier (1905), "The effective, moving, vitalizing work of the world is done between the ages of twenty-live and forty." . The ten years from twenty to thirty is the chief reproductive period, and therefore at this age most of the accidents of childbirth occur, t If all the ileal lis due to the puerperal slate in 1910, 15.5 per cent. were during this decade. The death rates from typhoid fever and from tuberculosis both reach their maximum at this time, but the latter is by far the most important, causing, in 1910, 35 per cent, of all the death- in this age. Middle Age. — The boundary between the age of maturity and middle age is distinctly marked in women by the climacteric, or menopause. This i> the ation of menstruation and oilier sexual functions, which usually occur rather suddenly between the of forty-five and fifty. In men, sexual activity diminishes al about tlie same age, but so gradually that many men have been able to beget children at a much later period of life. These changes are accompanied by other evidences of the approach of senility. The most noticeable of i is the turning gray of the hair. The dynamic ficient of the skeletal muscles begins to diminish thirty or forty years of life, and the plain muscles suffer a similar change, as is shown by the diminished t of the heart, intestines, bladder, and other organs. The lessened power of accommodation in the eyes is not so characteristic of this period as is generally supposed. According to Donders (1858), the power of accommodation is at its maximum in young children, when the lens is soft throughout. It soon begins to harden at the center, and as the Sclerosis gradually spreads toward the periphery there is a parallel loss of accommodation. The in- verse correlation between accommodation and age when plotted is represented by a straight line. The range of accommodation, measured in diopters, as given by Donders is At ten years 14 At twenty years 10 At thirty years 7 At forty years 4.5 After forty, 1 D less every five years. When the power of accommodation becomes so limited that it IS no longer possible to focus the eyes upon a small object near enough for clear vision, we have the condition known as presbyopia, which is characteristic of middle and old age. (See the articles on Accom- vwdalinn and Refraction and Eye, Dioptrics of.) The fatal diseases characteristic of middle age are heart disease, nephritis, and cancer. In 1910, they caused, in persons between fifty and fifty-nine years of age, 13.4, 11.7, and 12.1 per cent, of registered deaths respectively, and in persons between sixty and sixty-nine 18.2, 12.1, and 11.1 per cent, respectively. Senescence. — There is no sharp boundary between middle life and old age, but an individual may be said to have become senescent when, by reason of age, the decline of any of his bodily or mental func- tions has reached a point that renders him in- capable of continuing his previous occupation. This is apt to occur at about the seventieth year. The theories as to the cause of senility will be discussed in another article. (See Senility.) During this last period of life, heart disease reaches its maximum as a cause of death, and is the principal cause of that calamity. The next most important cause is cerebral hemorrhage, resulting from arteriosclerosis, the charac- teristic malady of old age. Robert Payne Bigelow. Rj it i:i NCES. Cameron, W., 1908, Children' Growth in Weight and Height. Pfaundler and Schlossmann, l'i e I Children, vol i . pp. urn 124. Chamberlain, A. F.. 1900. The i Ihild as a Study in the evolution • it Man. N. V.; Scribners. Crampton, ('. \\\, 1908 6. [ical V.gi , b I und intal Principle. Am. Phys. Educ. Review, voL xiii., pp. 1 n L54, 21 1- 227, 268 283, 34S 161 Donders,F C, 1864, Onthi Iccom dation and ,i,.ii ,,t the I ye. E 1 ] in bj w D. Moore, London: New Sydenham Soc. Forsyth, D., 1909. Children in Health and I Phila.: Blakiston. i, ter. Sir M., 1891. Textbook of Phj i Ed 6, Pt. 4, London: Macmiilan. II II. i ;. s . 1904. Wole ■ i'm.-. N. Y : Appleton. Heinricius, ('.., 1883. Ueber das Alter binn Eintritl der Menstruation bei 3500 Weibern in Finnland. Centralblatl fur Gynakologie, voL vii., pp. 72 73. Hill, C, 1909. Manual of Normal Histology. Phila.: Saunders. Ilobhousc, L. T., 1901. -Mind in Evolution. London: Mac- miilan. Mall, F. P., 1910. Determination of the Age of Human I Imbryoa and Foetuses. Keibel and Mall. Manual of Human Embry- ology, vol. i., pp. 1S0-201. Marro, A., 1901. La puberte chez l'homme et choz la femme. Paris: Schleicher Osier, W., 1905. Commemoration Address. .Johns Hopkins Univ. Bulletin. Pryor, J. W., 1005. Development of the Bones "f tin- Hand as shown by the X-ray Method. Bull. Stale College of Kentucky. Sec. 2, No. .5. Pryor, J. W., 1906. Ossification of the Epiphyses of the Hand. Bull. State College of Ky., See. a. No 1. Pryor, J. W., 1908. Chronology and t irder of Ossification of the Bones of the Human Carpus. Bull. State University of Kentucky, New Sec. 1, No. 2. Romanes, J. G., 1892. Darwin and after Darwin. Chi< ago: Open Court Pub. Co. Rotch, T. M., 1909. Development of the Bones in Early Life Studied by the Roentgen Method. Trans. Assoc. Am. Physicians, 1909. Tigerstedt, R., 1906. Text-book of Human Physiology, Ed. 3, Trans, by J. R. Murlin. N. Y.: Appleton. U. S. Census Bureau. Twelfth Census, 1900: Special Reports, Supplementary Analysis and Derivative Tables, 1906. U. S. Census Bureau. Bulletin 109. Mortality Statistics, 1910, 1912. Agenesis. — (Agenesia, from a, priv. +7e>«is, origin.) AVithout generation; without formation; without parents; unborn; undeveloped; failure of anlage; possessing no sex. From the latter meaning arose the conception of sterility or impotence, and the early use of the term in medicine was restricted to this meaning. Later, the idea of lack of sexual appetite became included in this, and the word was used by French writers especially with the meaning of anaphrodisia rather than with that of impotence. The word has now entirely lost its early significance and has acquired the technical meaning of total failure of development. A partial or imperfect development of parts whose embryonic foundations have been laid is not to be in- cluded in the significance of this term, but should be expressed by the words aplasia, hypoplasia, and hypogenesis. (See also Ateleiosis.) There is, nevertheless, much diversity of use among writers as to the exact significance given to each one of these terms. Aplasia in its original sense means a failure of restoration or rebuilding, but is now used with two meanings: that of a numerical atrophy, and that of a partial failure of development. By some writers the three words are used synonymously with the meaning of either partial or entire failure of devel- opment. A few authors also use these terms with the significance of atrophy. The present tendency is strongly in the direction of giving to each word a distinct place in technical terminology: to atrophy, that of diminution in size after development; to aplasia and hypoplasia, that of imperfect develop- ment; to agenesia, that of total failure of growth of the 151 Agenesis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES anlage or destruction of the part after it has begun to develop. Hypoplasia appears to have acquired the significance of a slight defect of growth; aplasia is used to indicate more important deficiencies. The term hypogenesia is now used by many embryologists to cover all forms of imperfect and arrested develop- ment, but particularly with reference to arrested de- velopment of primary and secondary growing points in the developing embryo. Fig. 57. — Partial Agenesia of the Bones of the Cranium in Aneneephalia. a, defect; /<, occipital portion; c, parietal bone; d, frontal bone. Reduced 1/5. (Ziegler.) The causes leading to imperfect development may operate at such an early period in fetal life that organs or parts may entirely fail of development (agenesia), or later, before the completion of growth, so that the affected parts are not of normal size (aplasia, hypoplasia). Fetal agenesias and aplasias play the chief role in the formation of monsters. The extrauterine aplasias affecting the develop- ment after birth may lead to a reduction of size of the entire body or extremities, and to an imperfect development of the sexual apparatus. Aplasia may affect the entire skeleton so that abnor- mally short individuals result (dwarfs), or the bones maybe unsymmetrically developed (partial dwarfism). The bones of the head are very frequently affected, giving rise to the conditions known as microcephalus and micrencephalus. The central nervous system may show defective development, with or without changes in its bony covering; one of the hemispheres may be abnormally small or the entire brain may show a retarded growth. Next to those of the nervous system, aplasias of the genito-urinary tract are most common in occurrence. The uterus or the entire set of female generative organs, external and internal, may remain in an undeveloped state at puberty. The external organs of the male are also not rarely abnormally small, and in non-descent of the testicle aplasia of the organ usually takes place. Parts of the intestine may be so imperfectly formed as to consist of a narrow canal or a small fibrous cord; and in the development of the lungs the alveoli of portions of one or more lobes may be imperfectly developed. The kidney and liver may also suffer a greater or less imperfection of growth. Hypoplasias of the heart and vascular system have been thought to play an important part in the pathology of chlorosis and lymphatic struma. Agenesia for the greater part leads to the production of monsters or to the development of malformations which may be of so serious a nature as to preclude the possibility of extrauterine life. There may be absence of the cranium (acrania) (Fig. 57), or of the brain (anencephalus), or of the spinal cord (amyelia). A complete failure of development of any part of the skeleton may take place, or of any part of the nervous system. Agenesia may also result from the failure of developing centers to unite or of clefts to close; in the hitter class are to be placed a great variety of mal- formations (cleft palate, hare lip, exstrophy of the bladder, spina bifida, cleft sternum, omphalocele, etc.). Agenesia of a single organ may also arise from the imperfect separation of two organs which develop from a single focus (cyclopia), or from the secondary union of two divided organs. Atresia of the mouth, nose, ear, anus, vagina, or urethra may also result from agenetic development of portions of these structures. Agenesia of the bones of the extremities, of single muscles or groups of muscles, of the auricular septum, etc., are among the more common malformations which permit of extrauterine life. The tissues composing aplastic organs may be normal in structure, but there is very frequently assi iciated with abnormal smallness of the entire organ a deficient development of its elements or a complete absence of the more highly specialized ones. In aplasia of the central nervous system there may be agenesia of the ganglia cells and nerve fibers; portions of the brain may be represented by fibrous or membranous masses. The hypoplastic ovary may show complete agenesia of its ova; and in the lung there may be entire failure of development of the alveoli (Fig. 58). Like- wise in the liver and kidney, portions of the secreting structures may fail entirely. The causes of aplasia and agenesia may be either in- trinsic or extrinsic. As intrinsic causes may be considered all of those that arise in the germ either through inheritance or pathological germ variation, or through disturbances of the copulation of the sexual nuclei. The inherit- ance of agenetic malformations may be direct, atavistic, or collateral. Certain types of faulty de- velopment, notably those of the nervous system and genito-urinary tract, occur with a certain fre- quency in degenerative inheritance (harelip, hypo- spadias, single kidney, monorehidism, syndactylism, deficient extremities, etc.). The pathological germ variation may be the result of the union of two nuclei, one or both of which are abnormal, or of the union of two normal nuclei which are not suited to each other. Premature exhaustion of the growing point or arrested growth of the same may be due to a reversionary degeneration with defective constitu- tion of the biophores, or to an intrinsic quantitative defect in matricial cells that should normally develop into certain organs or tissues. Chemical and physical influences may act upon the ovum or sperm before Fig. 5S. — Agenesis of the Respiratory Parenchyma of the Left Lung. The lung consists of dense connective tissue in the midal of which dilated bronchi are found. (Horizontal section through the apex of the upper lobe; natural size. (Ziegler.) fertilization as well as immediately after fertilization, and we know that agenesis and hypogenesis can be produced experimentally in this way (Roentgen ray, action of various chemicals, etc.). But by far the chief causes of agenesia are extrinsic. Of these, pressure, jarrings, disturbances in the supply of oxgyen and nutrition, contaminations of the mater- nal blood from intoxications and infections, fetal inflammations, abnormal conditions of the amnion, 152 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aggresslns play the most important part. There is very strong evidence that a large proportion of agenetic malfor- mations arise from abnormal adhesions between the embryo and the amnion, or from abnormal pre exerted by the amnion upon the developing germ. The head and extremities suffer most frequently from these causes. Aplasia of the bones is sometimes associated with thyroid disease. Agenesis and hypo- genesis are undoubtedly produced by many different causes; and in any given case of defective development ji uiay be impossible to determine the particular etiological factors. The agenesias of the more important structures of the body lead as a rule to the production of a non- viable fetus. Only those failures of development cting the body in such a degree that life processes arc not seriously interfered with admit of living after birth. Dwarfism, agenesia of the bones or muscle- of the extremities many of the cleft malformations, esia of the sexual organs, etc., permit of life and rauterine growth. Some of these may be corn- sated for by hypertrophy of other organs or parts of tin- same organ, while others may be improved by rical treatment. Aldked Scott Warthin. Ageusia. — (From tv-privative and yev W. 60.31 March 58.9 si; 7 31.1 35.3 3.3 23 2 3.2 4.0 w. 57.90 April 65 2 89 3 36.3 34.1 2.4 19.3 6.2 3 3 S.E. 52. 7S M: in 54 2 7S.8 26 6 35.3 2.9 19.0 5. 4 5 58 7; \Ve possess, then, in this climate all of the attributes of a health resort favorable for the relief of pulmonary tuberculosis, except altitude and its accompaniments — viz., pure dry air at a moderate temperature, a dry and well-drained soil, an absence of high winds with an occasional exception, and an abundance of sunshine. Experience through a long series of years m the treat- ment of pulmonary tuberculosis at this place verifies this conclusion. In the writer's opinion, the high- altitude climates are superior, as proved so far by results, to those without altitude; but it must never- theless be borne in mind that not all cases of pulmo- nary tuberculosis are suitable for the high altitudes, and in such a climate as Aiken we have a most valu- able resource for such cases as, from limited vitality or other unfavorable conditions, are unsuitable, at least fcir a while, for the high altitudes. Here we can surely carry out to perfection the modern open-air treatment, which after all is the essential part of the climatic treatment of pulmonary tuberculosis. Moreover, the climate of Aiken is suitable for patients who are suffering from other diseases, such as rheumatism and albuminuria; for convalescents from acute diseases or injuries; and for large numbers of individuals who, for one reason or another, possess little physical vigor. Here they can exist in comfort with a minimum expenditure of vital force. •Malaria," says the late Dr. Geddings, "is re- The Highland Park Hotel, which was destroyed by fire in 190S, has been replaced on another site by tin- Hotel Park-in-the-Pines, which compares favorably with the highest class metropolitan hostelries and is equipped as are few modern resort hotels. The special feature of the place is the cottage life, and cottage- of all sizes can be rented, from the simple three-room cabin to the pretentious villa provided with all the modern improvements. There are four family hotels in the town, and also numerous boarding- houses. Any account of Aiken would be incomplete without mention of the small but excellent Aiken Cottage Sanatorium founded, in 1S96, for the treatment of cases of incipient phthisis. It is a charity, and is modelled after the institution of Dr. Trudeau's al Saranac Lake. The cottages at present are arranged to accommodate sixteen patients. The treatment consists mainly in providing good nourishment and keeping the patients in the open air from seven to nine hours a day. The educationaf advantages of Aiken are very good, there being several excellent junior schools, and a high school which fits its pupils for college. Churches of all denominations are to be found here. In conclusion it may be added that Aiken is situated upon the Southern Railroad, with three daily trains from New York, For much of the above account the 156 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Airiliiini writer is indebted to the late Dr. Mc< iahan, one of the founders of the Aiken Cottage Sanatorium. Edwabd < ». Otis. Allanthus. — A genus of some seven species, in the family Simarubacece, natives of Eastern Asia and the East Indies, the A. glandulosa Desf. common in the Eastern United States. It is in this species thai Ileal interest chiefly centers. It has been observed that the tree is odious to flies, which, it is said, will not approach even decayed meat when placed among its leaves. Mild poisoning has been recorded from the habitual drinking of water into which the roots of the tree had penetrated, and i\ hidi its leaves had fallen. The symptoms were those of simple gastric irritation, similar to what would be caused by the amaroids contained in quassia and similar drugs. The bark and leaves have been I medicinally, and are purgative and anthelmintic. I b.< constituents of the plant are known only in the mosl general way. An amaroid, a volatile oil, and i resin are active. The pure resin has been found purgative, but not anthelmintic, while the oleoresin is an efficient teniacide. The teniacidal property is therefore assumed to reside in the dark-green volatile oil. This oil, taken by inhalation, is a powerful depressant poison, producing vomiting, dizziness, and cold perspiration. Taken by the stomach these effects have not been observed, though due pre- cautions in regard to dosage should be observed. The dose of the powdered leaves, as a teniacide, is 0.5-2.0 grams (grain viij. to xxx.), of the oleoresin 0.2 to 0.6 gram (grain iij. to x.). In India, the juice of the leaves and bark of .1. exeelsa Roxb. have been used from ancient times as a tonic, especially in convalescence after parturition. The bark of this and of A. malaharica D. C, is also used as a vegetable bitter, in forms of dyspepsia. II. II. RUSBY. Ainhum. — (Synonyms: Ainhun; dactylolysis spon- tanea; Absiigen [German]; Daetiliolisia [Spanish].) The etymology of the word is usually attributed to Africa, and is derived from a word meaning to "saw off." Matas states that the word ainhum is from the negro patois of Brazil, ainhoum, meaning a "fissure." Definition. — Ainhum is a disease of tropical countries, and is characterized by the gradual painless amputation of one or more joints of one or more toes by a trophic process of mixed atrophy and hypertrophy. History. — While the first accurate description of the disease was made by da Silva Lima, of Bahia, Brazil, in 1S67, as much earlier as 1860 Dr. Clark called attention to ainhum in the Gold Coast natives. Since 1S67, a number of observers have reported upon the disease, notably Duhring and Wile, and Matas in this country. Zambaco Pacha, in the Transactions of the 1897 Lepra Conference in Berlin, writes at length upon the condition in its relation to leprosy. Etiology. — The cause of the disease is not known. It has been found in the negro races in most of the - reported; it usually occurs in adults, though de Brun reports a ease at six years of age, and is essentially a tropical disease, exotic cases occurring occasionally elsewhere. The parasitic nature of the disease is maintained by some, but it has not been proven. Zambaco Pacha maintains the identity of ainhum and trophic leprosy of the mutilating type. Hanson suggests that the lesion is due to irritation from injuries received in walking barefooted, resulting in the peculiar scarring, like keloid, to which the negro race is especially prone. Symptoms. — Prodromes are absent. There may be some itching, but usually the disease is evidenced by a slightly constricting band, a furrow, at the digitoplantar fold of the fifth toe. At times other toes may be affected. For example, I have seen the great toe involved, at the New Orleans Charity Hospital. The furrow gradually becomes more pronounced, harder in consistency, and more and more constricting, the confined portion of the digit increasing in size SO as to lose the shape and form of a toe. There is absence of inflammation and of sub- jective symptoms, excepting occasional pain. As Fig. 61. — Ainhum, End of Small Toe after Amputation. (Enlarged about 2 1/2 times.) the constricting band narrows, the toe becomes more and more tumefied, until finally only a small pedicle remains. From this the tumor either sloughs off, is torn or knocked off, or is intentionally removed. When ulceration takes place, there is a distinct odor, of a nauseous character, resembling that of the neurotic ulcer. The pedicle, or base, heals kindly. The process lasts months — even years in some instances. Pathology. — Unna believes the condition to be "a ring-formed scleroderma with callous formation of the epidermis, leading to secondary total stagnating necrosis, resembling artificial snaring of tumors. There is a primary inflammation with marked hyper- trophy of the epidermis, the papilla? being narrowed and elongated. In the papillary body there is cellular infiltration; the vessels are dilated. The tumefaction of the toe indicates a stagnation of lymph and fat, whicli gradually causes degeneration of all of the constituents of the cutis, a rarefaction of the bones, and the disappearance of the phalanges. In this most observers agree. Differential diagnosis must be made especially from Raynaud's disease, from paronychia, from the neurotic ulcer, and from leprosy. Raynaud's disease is nearly always painful, occurs seldom on the lower extremities, is quite common on the upper extremities, and the trophic change is evidenced most often by the occurrence of preliminary lesions, e.g. vesicles or bulla?. Paronychia is inflammatory throughout and occurs on the ungual phalanx always. The neurotic ulcer begins as a callosity, is circum- scribed and deep seated, occurs usually on the plantar surface of the heel or great toe, and is never located just at the digitoplantar fold of the fifth toe. It is 157 Ainhiim REFERENCE HANDBOOK OF THE MEDICAL SCIENCES characterized almost from the start by the loss of the central tissue and by a persistent slough, exulcerating and discharging freely. Leprosy of the mutilating type has points of resem- blance to ainhum, especially when the latter disease is well advanced. Leprosy, however, has no prefer- ence for the negro, and it is not a tropical disease. The trophic lesions of leprosy are found on any toe or any finger, usually on the dorsal side. These are almost invariably associated with other present or past manifestations. The initial evidence of muti- lating leprosy is a macule, excoriation, or bulla on the site of the destruction. The initial evidence of ainhum is a callous furrow, without inflammatory redness. Treatment. — All observers agree that perpen- dicular and free incision of the circular bands may arrest the process, but that usually the course of spontaneous amputation is completed, unless arti- ficially or surgically produced. Isadore Dyer. Bibliography. Clark: Trans. Epidemiolog. Soc., I860, London. Da Silva Lima: Ainhum. Amer. Archiv. of Dermat., 1SS0, p. 367. Duhring and Wile: Ainhum. Amer Jour. Med Sciences. January, 1S81. Eyles: Lancet, 1886. ii, p. 576. Walter Pyle: Medical News, Jan. 26, 1S95 (with full bibliog- raphy). DeBrun: Annales de Dermatologie, vol. x (1S99), p. 325. X. D. Brayton: Journal of the American Medical Association, July 8. 1905. Air. — To appreciate the various sanitary relations of the atmosphere, the subject must be studied from the physical as well as from the chemical stand- point. In considering the physical aspects of air, attention must be given to the subjects of atmos- pheric pressure, light, heat, humidity, and electrical condition. Physical Properties. 1. Atmospheric Pressure. — The air is an invisible gaseous ocean. In it, as in all gases, there is no cohesion between the molecules. They are apart from one another, and their tendency to spring farther apart and occupy more space is so great that a restraining force is needful to prevent expansion and attenuation. Air at the sea level, the bottom of the aerial ocean, is compressed b}- the weight of the superincumbent air. This weight ex- presses the influence of gravity on the air as a whole, or the influence which the earth exerts on the mole- cules of its atmosphere to keep them from escaping into limitless space or from being whirled away by the centrifugal force of the diurnal rotation. The pres- sure of the atmosphere at the sea level balances a column of water thirty-four feet high. It forces water up the cylinder of a pump in proportion as the air pressure within the cylinder is lessened by the working of the piston, but the raising power of the pump is limited by the height mentioned. Similarly at the sea level the atmospheric pressure balances a column of mercury 29.92 inches, or 760 millimeters, in height (at 45° N. latitude), and as this number of cubic inches of the liquid metal weighs 14.75 pounds, or 1 kilogram, to the square centimeter, the air pressure on every measure of surface becomes known. Generally, however, air pressure is expressed in inches of mercury as being more convenient than a state- ment of the actual weight on a given area. The pres- sure on a surface of one square foot amounts to nearly a ton. The average man has a surface of about fifteen square feet, but the fifteen tons of air pressure under which he moves are unfelt because of the fluidity of the atmosphere. The freedom of movement possessed by its molecules transmits their pressure in all directions. Air permeates all porous bodies, and the internal pressure in bodies so permeated counter- acts the external pressure. Noticeable effects of air pressure are seen or felt only when there are local disturbances, as when the tissues are pressed by the weight of the atmosphere into the rarefied air of a cupping glass. The higher we ascend into the atmosphere the less is the pressure, because there is less overlying air to affect us by its weight. Heights are measured by the decreased pressure, and balloonists calculate their distance from the earth by the fall of the mercurial column in their barometers. At the sea level, under a pressure equivalent to that of 29.92 inches of mer- cury, a cubic foot of air weighs 536 grains. Air is increased in bulk as pressure is diminished. At the height of one mile, the barometric column falls to 24.5 inches, equivalent to a pressure of 12.04 pounds to the square inch. Under this lessened pressure, a cubic foot of sea-level air would expand, other things being equal, to 29.92-^24.5, or 1.22 cubic feet, and one cubic foot of this rarefied air would weigh only 439 grains. The pressure at two miles being equiva- lent to only twenty inches of mercury, one cubic foot of sea-level air would expand to 29.92-^20, or 1.49 cubic feet, and the weight of a cubic foot of this expanded air would be 360 grains. With increased height there is diminished density, but as the elastic force which separates the molecules becomes lessened by their sepa- ration, there may be a certain condition of tenuity in which this force is unable to overcome those which operate in restraint. The depth of the atmospheric ocean has been estimated variously at from 45 to 350 miles or more. 2. Light. — Light from the sun or other sources passes through the air without illuminating it. Were it otherwise we should be able to see the air. We see things by the light which they emit or reflect, but the air merely transmits. We speak of atmospheric glows and beams of light, of the blue of the firma- ment and the radiance of morn, but these pin relate to the visibility of substances in the air. Light is transmitted in straight lines, with the exception of some refraction in the denser strata near the earth's surface; but as more or less of the light is refused a lodgment by every substance on which it falls, and is reflected from one object to another at all angles and hence in every direction, the whole of the air is filled with rays which illuminate objects that are not exposed directly to the source of the illumination. Molecules of watery vapor and minute particles of dust suspended in the air give rise to the apparent diffusion of light in the atmosphere. These account for the dawning light of morn, and the twilight after sundown. 3. Heat. — Associated with solar light are actinic and heat rays. The latter are of the highest interest, as being the cause of the tides, currents, and local move- ments in the atmosphere. Heat rays pass through the atmosphere without warming it. The air of high mountain regions is cold, although the same rays pass through it which may give a tropical warmth to the plains below. It is usually said that the temperature falls 1° F. for every 300 feet of altitude, or about 134 meters for 1° C. This, although not accurate, is useful. If the temperature, average or actual, of a given locality be stated, an approximation to the corresponding temperature of a neighboring plateau may be calculated. Glaisher, during his balloon ascents, found the temperature on a cloudy day lowered 4° F. for every inch of a barometric fall of eleven inches; and the further ascent was marked by a more rapid refrigeration. As eleven inchc- oi mercury indicate an elevation of 12,000 feet, the average ascent for the Fahrenheit degree was a I 270 feet. On a clear day the thermometer fell 5° for each of the first four inches of barometric fall, 4° for each of the next nine inches, and 13.5° for the last three inches of his ascent. The cold is propor- tioned to the lessened pressure, 4° F. for each inch; 1 ,-,s REFER EXIT. HANDBOOK OF THE MEDICAL SCIENCES Air but as the height to bi> ascended fur each inch of f ;l ll increases with the ascent, the height for each degree of temperature increases correspondingly. Air, in expanding under lessened pressure, lias its expansion restricted in some measure by the loss of heat attending the expansion, for the volume of a gas is contracted by cold. Air expands T J, T of its volume at 0° F. for each degree of increased tempera- ture Os+j in the case of Centigrade). Hence 460 cubic inches or feet or, in general terms, volumes, at 0° F. expand at 60° to 520 volumes, and conversely by a reduction of temperature from 60° F. to 6° 520 olumes contract to 460. On these data is based that which in dealing with air and gases is called the "correction for temperature." The molecules of a . ubic foot of dry air weigh, at the sea level, 536 grains. Under the diminished pressure, at 16,000 feet, these molecules would occupy a space of two cubic feet, each foot containing 26* grains; but the coincident reduction of temperature would so modify this that the cubic foot of air would weigh 303 grains. The rarefaction of the atmosphere in mountain regions is thus seen to be somewhat less than we should be led to expect by a consideration merely of the barometric pressure. Heat, like light, is absorbed in varying proportions by everything on the surface of the earth, and that which is not absorbed is reflected at various angles, so that the air in its lower strata is filled with reflected rays which become manifest only when they arc absorbed and increase the temperature of the ab- sorbing substance. Absorbed heat is radiated to cooler bodies in the neighborhood, for the tendency in nature is to an equable distribution. Hence, besides reflected rays, the air may be filled with rays of radiant heat, but in all this there is merely trans- mission, with no appreciable influence on the air itself. When, however, absorbed heat is distributed by convection the air assumes an active part in the process. A warm substance communicates part of its heat to the air molecules in immediate contact with it. The air thus heated expands and is floated upward by the inflow of colder and heavier air beneath it; and it is thus raised until by admixture with the general mass of the air its rarefaction is lost, or until under unusual conditions of placidity it reaches a stratum of equal rarefaction. The cold air that replaced it in contact with the heated substance becomes similarly warmed and borne upward; and this continued in an uninterrupted sequence gives rise to an upward current of warm air with inflowing currents of colder, heavier air on all sides. We sometimes seem to see this upward current by the side of a heated stove, when its varying density dis- turbs the passage of the rays of light from objects seen through it, and gives a quivering movement to their outlines. In the sandy districts of southern Arizona and New Mexico, trees and other objects at a little distance from the observer are often tremu- lously distorted to his sight by the upward currents from the sun-heated surface. Objects that absorb much radiate much, and those warmed rapidly by absorption cool quickly by radia- tion. Color has an influence on these movements, for black surfaces absorb and radiate better than white. Radiation and reflection are therefore different pro- cesses, for white is the better reflector. The radiant powers of different substances vary much, but it is unnecessary here to do more than indicate in general terms the differences presented by land and water in this regard. As compared with water, land heats quickly and cools quickly. The heat does not penetrate but ac- cumulates in and immediately beneath the surface Children know how cool is the underlying sand turned up on the seashore in their holiday play. The surface is hot by day and cool by night, but at a depth of three feet there is no diurnal increase of temperature, and even the heat of a prolonged summer penetrates only about seventy feet, for well water at this depth has the same temperature summer and winter. .Masses of water, on the other hand, heat slowly and cool slowly; the rays penetrate to the depths. The temperature of the surface waters of the ocean is never over 80° F. (26.6° C.) in the tropics, and its diurnal range is small. In higher latitudes the temperature is lower, bul the mass of the waters of the ocean, in both high and low latitudes, is never below 39° I'. (3.9° O). Thus the air is warmed intermittently by the land and continuously by the ocean, and its molecules are kept in motion by the convection which is in progress. The solar rays are the only source from which the air derives its warmth, for, although animal life and the combustion of fuel develop heat, the heat thus developed is merely the liberation of energy derived originally from the sun. Again, although the earth has an internal heat, this heat is not transmitted through the crust, for the superficial strata to a depth of seventy feet are affected by the seasonal warmth of the sun, and not by the interior heat. 4. Humidity. — The effects of heat on the atmos- phere are multiplied and varied by the phenomena attending its action on water. Vapor, invisible as the atmosphere itself, rises from water at all tempera- tures. The higher the temperature the more rapid the evaporation. Thus vapor is absorbed into the atmosphere, and the amount that can be absorbed increases with increase of temperature. A cubic foot of air at 32° F. is saturated with moisture when it contains 10 cubic inches or about two grains of vapor of water; but at 100° F. (37.8° C.) the cubic foot of air can absorb about 100 cubic inches, or nearly 20 grains. The molecules of the vapor find place for themselves in the intermolecular spaces of the air, but not without crowding aside the air molecules to such an extent that saturated air is lighter than dry air. Air is known to be saturated when the slightest lowering of its temperature causes a deposition of moisture. We call such a deposition cloud when in the air above us, fog or mist when in the air around us. and dew when deposited at night on vegetation and other highly radiating surfaces. The dew point may be found by noting the temperature at which moisture appears on the outside of a test tube, cooled by the evaporation of ether in its interior. Usually an approximation to it is obtained by the wet bulb thermometer, from which the actual dew point may be calculated or gathered from Glaisher's tables. Moisture in the air is expressed as relative humidity on a scale of which 100 is the point of saturation. Absolute figures give no satisfaction. With two grains of moisture in a cubic foot of air the air, as we have seen, may be very moist or very dry. If the temperature is 32° F., the air is saturated; if it is 100° F., the air is so dry that it is ready to take up eighteen grains more before it becomes saturated. Evaporation aids radiation and convection in cool- ing a warm, moist surface. The soldier in a summer camp moistens the outside of his canteen and hangs it on a branch that the passing breeze may cool its con- tained water. Even the surface of the water of the tropical oceans is cooled slightly at night. It is, how- ever, not so much by the production of a local coolness as by the transference of heat from one place to an- other that the chief influence of evaporation is ex- ercised. From the surface of the ocean, particularly in the warmer latitudes, evaporation is going on at all times. An upward movement of moist, warm air is continuously in progress. Partial condensation occurs by the time this air reaches a stratum of its own density, but the clouds there formed are usually hurried by air currents to other and colder regions of the globe before the particles of condensed vapor become aggregated and fall as rain. The heat gathered from the tropics is thus distributed to other 159 Air REFERENCE HANDBOOK OF THE MEDICAL SCIENCES pari- of the earth, the air of which is warmed by con- densation above as well as by convection from below. Moreover, the clouds absorb heat radiated from the surface of the earth, thus preventing its dissipation into the ether beyond. Every object on the surface is thus kept warmer than it otherwise would be. Clouds act as a blanket to keep the air and the earth under them warm. Any roof, however flimsy, even the spreading branches of a tree in foliage, is a pro- tection against the cold of radiation into space. The great heat of the direct rays of the sun at high alti- tudes, where the surrounding air is intensely cold, is attributed to the freedom of the air from intercepting moisture. 5. Electrical Condition. — Electricity pervades the atmosphere. It is generated by the evaporation of water, the friction of the wind on the surface, and of the molecular constituents of the air each on the other; but its relations to these constituents are not clearly understood. It is greatest in cold, dry weather, but the greatest electrical disturbances are associated with condensation and rainfall. ( )ur knowledge of the effects of heat and moisture enables us with but. little effort to recognize the causes of many meteorologic phenomena that have important bearings on the well-being and comfort of the human race. Meteorology is probably the oldest of the sciences, for man, even in the earliest days of his racial existence, found it necessary to study the probabilities; and the weather wisdom of every nation is embodied in proverbial expressions. The co- operative work of modern times, made possible by the use of the telegraph, has enlarged our knowledge and broadened our views of these phenomena, so that we now have a useful understanding of the general as well as the local movements of the atmosphere. Air Currents. — Extending for a few degrees on each side of the equator is a region of calm and light varia- ble winds, known to sailors as the doldrums. Here the uprising of the moist, warm air leads to condensation in the higher strata. Heavy rains fall, and the heat liberated during the condensation rarefies the relative- ly dry air of the upper regions and develops a swell on the surface of the atmospheric ocean which divides or flows over, one-half to the north, the other to the south, while an inflow in the lower strata restores the aerial equilibrium. The inflowing currents do not come from the poles; they reach only from the thirtieth parallels, and their motion is more or less obliquely from the east on account of the diurnal revolution of the earth. A belt of variable winds is found about the thirtieth parallels. Here the upper current from the tropics impinges (in the northern hemisphere) on a northeast upper current from the Arctic circle, and the swell of their meeting occasions an increased pressure at this point. Escape for the accumulated air is found below, southward constituting the trade winds and northward constituting the regular south- west winds of the north temperate zone. At the Arctic circle is another doldrum belt into which flows the wind last mentioned and a surface current from the northeast. These, warm and cold intermingling, produce condensation and rainfall and an expansion or swell which overflows into a northeast upper current over the temperate zone, and a southwest upper current toward the pole. The surface currents affect the air to a height of 10,000 feet, involving about one-half of the weight of the atmosphere, and their velocity averages about fifteen miles an hour. This constitutes the general circulation of the atmospheric ocean, but there arc many secondary currents, as that between land and sea. In fact innumerable causes of greater heating at one place than at another give rise to local currents. The resultant of all the meteorological conditions constitute climate; but temperature, as being the most notable condition, is usually adopted to give formal expression to the character of a climate. Temperature depends on latitude, altitude, and the presence of large bodies of water to reduce the daily and seasonal ranges. One of the first discoveries by those who collated the meteorological observations of the medical officers of the United States Army was the climatic importance of the great lakes. In New England the influence of the ocean was found to modify the mean temperature. In the interior of New York, the daily range increased and the seasons were strongly contrasted. Farther west, near the great lakes, a climate similar to that of the seaboard was again found, but in the interior beyond them, ex- treme changes again became the rule. Water tempers the winds which blow over it and loads them with vapor for subsequent condensation and warmth. The regular southwest winds of the temperate zone reaching Europe from the Atlantic and California from the Pacific Ocean give these shores a climate markedly different from that of the Eastern coast or interior of the United States. The air of continental interiors is dry and the solar rays beat with full in- tensity on the surface, while at night there is no pro- tection against radiation into the cloudless skies. That climate has a powerful influence on the welfare of man is manifest when we compare the weakness and indolence of tropical races with the strength and energy, mental as well as physical, of those of the temperate zones. Since the earliest ages it has been a favorite theory that diseases come upon mankind through the air. But although the tendency of modern research is to absolve the air from any special complicity in the propagation of epidemic diseases, the charge of influencing the human system unfavor- ably still holds good in certain other respects. Altera- tions of atmospheric pressure have been regarded by some medical observers as causing pulmonary con- gestions, and both compressed and rarefied airs have been used in the treatment of diseased conditions of these organs. In hospitals for consumption, how- ever, where any general influence causing congestion of the lungs would be manifested by an increase in the number of cases of hemoptysis, careful observation has shown that there is no such increase during the passage of the storm center. The exacerbations of neuralgic and rheumatic pains coincident with alterations of atmospheric pressure have established a popular belief in their relations as effect and cause, which has received some support from a consideration of "caisson disease." The caisson for the Brooklyn tower of the East River Bridge measured 168 X 102 feet, its interior or working chambers being fourteen feet in height. It was, in fact, a huge box sunk mouth downward by laying courses of concrete on its upper surface. Compressed air forced into the chambers displaced the water; and relays of men excavated the bottom of the river bed beneath it until a rock foundation was reached. The upper end of each shaft leading to the chambers was guarded by an air-lock to prevent injury to the men by a sudden change of pressure on entering or leaving. Before descending, compressed air from below was admitted gradually into the lock chamber, and only when the density was equal to that in the caisson was the descent made. Correspondingly, before leaving, a gradual transition from compressed to ordinary air was effected. On exposure to air under a pressure of three or four atmospheres, the skin became pale and shrivelled and the countenance shrunken, as the blood was forced from the superficial vessels to those of the bones and the cavity of the skull. The heart's action increased in rapidity to oxer- come the impediment to the circulation; but after a time the system accommodated itself to the altered conditions, and generally no bad effect was manifested until the men returned to the colder and relatively rarefied air of the surface, when many suffered from pains in the bones, giddiness, faintness, numbni and even paralysis. A longer time in the lock chani- 160 ItKI'KKKNCK HANDBOOK OF THE MEDICAL SCI] NCES Air ber td permit of accommodation to lessening air , . would have prevented these injurious effect - Phe diminished pressure at high altitudes is described by travellers as causing soroche, or mountain sickness, which is characterized by restlessness, sleeplessness, ping respiration, anxiety, vomiting, and fainting, ft is experienced al a height of ten or twelve thousand when the individual is expending energy by climbing, but in balloon ascents the effects of dimin- ished pressure are not felt until twice this distance has been reached. Heat relaxes the tissues and depresses the vital energies. Cold stimulates these energies to make good loss of animal heat; but if excessive it benumbs and paralyzes and ultimately destroys by freezing. When local in its application it disturbs the cireula- uf the blood, causing a congestion of some internal in when the surface of the body is chilled and its els are contracted. Air at 50° F. (10° C.) saturated with moisture is colder to the feel than dry air at the same temperature; it chills by contact. Above 50°, however, it is warmer, prevents evaporation from the body. At high tospheric temperatures it is oppressive and induces exhaustion or sunstroke. As evaporation is stopped, the system is unable to keep down its heat to normal of 9S.6° F. (37° C), and when the blood becomes heated higher than this, dangerous symptoms leveloped. i in mical Constitution. — Formerly air was re- garded as one of the elements. It is now known to be a composite substance; the properties of its constitu- ents have been determined, their relations to animal and vegetable life have been discovered, and traces of idental impurities swept up by its currents from the face of the earth have been detected and studied in their bearing on sanitary conditions. The atmos- phere, according to the chemist, consists of a mixture of two gases, oxygen and nitrogen. The former is active in its properties, combining with many suscept- ible elements, and especially with the carbon and hydrogen of devitalized organic matter, constituting, ording to the rapidity of the process, either oxida- tion or combustion, and, with the same elements in the living tissues of animals, constituting one of the itials for the continuance of life. A certain small percentage of the oxygen of the air exists in the form of ozone, but the quantity present cannot be deter- mined, and even its existence is at times indicated with doubt by the iodized starch papers, which have been largely used for its detection, as they are affected by other matters, as nitrous acid and peroxide of hydrogen, occasionally present in the atmosphere. Iodized litmus papers have been shown by Dr. Fox to be of value as a qualitative test, and as indicating comparative quantities when known volumes of the air are aspirated over them. It is certain, however, ozone has stronger affinities than ordinary oxy- gen, and that oxidation goes on more rapidly in its presence than in its absence. It undoubtedly de- stroys the volatile substances which are evolved dur- ing the putrefactive process. When foul organic odors are present, ozone is absent. Hence, when the presence of ozone is indicated by the test papers, the air is regarded as free from organic contaminations susceptible of oxidation. Animals exposed to ozone artificially produced suffer from irritation of the lungs. The n ilrogen is regarded as negative, or passive, serv- ing merely to moderate the activities of the oxygen by dilution. Mention, however, should be made of the discovery of the element argon by Lord Rayleigh and Professor Ramsey. Argon has characters similar to those of nitrogen; but as its uses in the economy of nature have not as yet been determined, it must be left for the present with the nitrogen, with which it has so long been associated. In the atmosphere the chemist recognizes also the presence of small but varying quantities of other mat- ters such as carbon dioxide, ammonia, and watery vapor. The percentage composition of dry air i-. by volume, 79 of nitrogen, 20.96 of oxygen, and 0.04 oi carbon dioxide; by weight the relative proportions of nitrogen and oxygen, are 76.99 and 23.01. Nitrogen is the lightest, carbon dioxide is the heaviest; yet, on account of the const ant I not ion of the atmosphere and the tendency of gases to diffuse, there is no separation into st rat. a richer in nitrogen above and carbon dioxide below. This power of diffusion possessed by gases is such that, in places where t here is a continuous genera- tion of carbon dioxide, it does not accumulate un- less it is confined as in a room, and even t hen it is dif- fused through the whole air of the room and not col- lected by its weight near the floor. The intermingling of gases by diffusion is shown by I'ettcnkofer's exami- nation of the air over certain effervescing springs. Samples from the water level contained 70 per cent, of carbon dioxide; from 40 inches above the water level, 2 percent., and from 5.5 inches only 0.5 percent. Hence little difference is found in the percentage composition of the free air, whether samples be taken from over the land or the ocean, from the sea level or from a high altitude. The oxygen of the air varies but little from its average percentage, but the quantity of it taken into the lungs varies with the temperature and pressure. Much of the depressing effects of atmospheric heat is probably due to a want of oxygen in the expanded air. A cubic foot of sea-level air at 32° F. contains 132 grains of oxygen; at 100° F. it contains 116 grains, a reduction of 12 per cent. Again, the distress felt by mountain climbers and usually ascribed to lessened pressure, is probably due in great part to the lessened amount of oxygen inhaled. A cubic foot of air, at 60° F. and 30 inches of pressure, contains 124.6 grains of oxygen. The expansion under a barometric pressure of 20 inches, corresponding to a height of two miles, with the coincident contraction by a fall of tempera- ture to 20° F., would reduce the oxygen in a cubic foot to 90 grains, a reduction of 2.8 per cent. The carbon dioxide, C0 2 , familiarly (but incorrectly) known as carbonic acid, is produced by the oxidation of carbon in dead and living tissues, and its percentage in air varies with the local causes which determine its production. Thus it is greater in the alleys and streets of a city than in the open country, and as this gas is soluble to some extent in water, its proportion varies with the hygrometric and other conditions, being greater in a damp atmosphere before rain has fallen than in the air of the same locality after the aqueous vapor has been precipitated. The air cur- rents and the diffusive power tend to equalize the percentage, but as production is constant in some localities, the air of these must always show a rela- tively larger quantity of this gas than that of others remote from such sources. The proportion in the external air seldom exceeds 4 volumes in 10,000. De Saussure made many series of observations to deter- mine the percentage under various conditions. In an investigation of the ventilation of soldiers' quar- ters, at Fort Bridger, Wyoming, in 1S74, there was found in the external air a gradual decrease, day by day, from 4.5 to 2.6 volumes per 10,000 as the season advanced, and the surface of the earth became covered with luxuriant vegetation. Carbon dioxide is a product of combustion; it will therefore not support combustion. It is a product of respiration, therefore it will not support respiration. In mines, life is in danger when a candle will not burn. Because workmen in soda-water factories suffer no inconvenience in breathing an atmosphere containing as much as two per cent, of carbon dioxide, many have supposed that this gas is not poisonous, but that, like water, it drowns fire and life alike by preventing the access of oxygen. Nevertheless experiments have shown it to be actively harmful. Animals breathing it along with as much oxygen as is present in the Vol. I.— 11 161 Air REFERENCE HANDBOOK OF THE MEDICAL SCIENCES atmospheric air have the heart's action weakened even to fainting, and when man is the subject of the experi- ment, dulness of mind culminates in unconsciousness or stupor. This, however, is not of much practical importance, for the sources which furnish carbon dioxide to the atmosphere generally yield with it other and more dangerous substances. Ammonia is diffused from putrefactive processes in progress on the surface of the earth. It is also pro- duced, in traces, from the nitrogen of the atmosphere by electric agency. Its quantity is variable, but 0.1 milligram in a cubic meter of air is a not unusual amount. This corresponds to a grain in about 23,000 cubic feet. Rain washes the ammonia from the air to the surface of the earth in amounts varying from 0.2 to 0.5 part per million of the rain water. The im- Erovement in fields which are permitted to lie fallow as been attributed to ammonia in the rainfall, but this ammonia is manifestly inadequate to account for the masses of vegetation which annually find nourishment in the soil. The ammonia originating on or in the soil during the decomposition of its organic matters is the source of the nitrogen which feeds the living plants. A trace only of this ammonia escapes into the air and is afterward washed down with the rain. Prior to its use by the vegetation which covers the surface of the earth, it is nitrified by bacteria which are everywhere present in the upper layers of the soil. Some of the lower forms of vege- table life, such as certain alga? and bacteria, absorb nitrogen directly from the atmosphere. Some legu- minous plants also fix atmospheric nitrogen in their tissues, but this is accomplished indirectly through the medium of parasitic bacteria found in nodules on their roots. The ammonia of the air is condensed on exposed surfaces, and R. A. Smith has suggested that the quantity of ammonia deposited on a given surface in a given time may be taken as an exponent of the sanitary condition of the atmosphere. A glass or other surface which has been exposed for some time in an unventilated bedroom, when washed with pure water will show in the washings the presence of a readily determinable quantity of ammonia; but the attempt to demonstrate the relative purity of atmos- pheres by the quantity deposited on equal and similar surfaces in equal periods of exposure meets with failure unless the temperature, the hygrometric con- dition, and the air movement are the same in both instances. This concurrence of similar conditions is difficult, if not impossible, to obtain in practice. The air constituents which have been mentioned must be regarded, from the scientific and sanitary point of view, as individually essential to the consti- tution of the atmosphere. The oxygen is vital to animals, its quantity being preserved by the evolution from vegetation and the equilibrium established between these two kingdoms of nature. The carbon dioxide is vital to vegetation, being the source of the carbon solidified in its tissues; its quantity is preserved by the evolution from animals and the retrogressive metamorphosis of the organic carbon of devitalized tissues. For our present purpose organic substances may be considered as those developed by the forces of life. They include all living bodies and those that have ceased to live, with many products of the life of the one and of the decay or decomposition of the other. With the infinite variety of animal and vegetable life constantly before us, it is needless to suggest the com- plex character of organic matters, but, notwithstand- ing this complexity little more than the elements contained in air and water enter into their composition. Animal life depends on vegetable life for its suste- nance directly, or in the case of carnivorous animals in- directly. Animals cannot combine the elementary bodies, but these are taken by plants and formed into organic substances, which animals are capable of util- 162 izing as food. So complex are all vitalized substances that but for the preservative influence of their vitality, their molecules would speedily break up into simpler forms, and, indeed, when life ceases to protect them their putrefactive decomposition begins immediately and ends in their resolution into the very substances from which they were originally constructed. Nature moves in cycles. Day follows day and season season. The seed germinates and the grown plant matures its seed. Every generation is a cycle, and, in the instance before us, the elements from which life elaborated the highest organic structures revert to the inorganic condition of carbon dioxide, ammonia or nitrates, and water for use in some succeeding cycle. Even in the living organism similar changes take place. No machine works without wear. The tissues of the animal body are worn by exercise. The nitrogen of the worn-out tissues is removed by the kidneys as urea, which speedily becomes converted into ammonia, while the carbon is oxidized and the resulting carbon dioxide is carried to the lungs to be expelled. During quiet breathing twenty-seven cubic inches of air enter the lungs at each inspiration, and if the air be pure nearly six of these cubic inches are oxygen and only one one-hundredth part of a cubic inch carbon dioxide. The air expired has less oxygen, more watery vapor, a taint of organic matter, and some- what more than a cubic inch of carbon dioxide. Breathed air, therefore, contains a hundred times more carbon dioxide than is contained in an equal volume of the free atmosphere. The frequency and depth of the respiratory acts vary in the individual with his condition as to health, exercise, or repose; and as might be expected, they vary also in different individuals under the same or similar conditions. The average excretion of carbon dioxide by the human lungs can therefore be stated only approximu 1 Giving due consideration to the experimental results obtained by various qualified investigators, its amount may be stated to be at least 0.01 cubic foot per min- ute, 0.6 per hour, or 14.4 in the twenty-four hours. The energy of the vital actions concerned in respira- tion, may be appreciated when we realize that in 14.4 cubic feet of this invisible gas we have nearly half a pound of solid carbon. Although the inflow into the lungs is interrupted by expiration at comparatively regular intervals, the absorption of oxygen and evolution of carbon dioxide are continuously in progress. The inspiratory inflow of twenty-seven cubic inches mixes with the air already in the lungs and freshens it for the use of the system. Deep breathing washes out the lungs and permeates them with an air rich in oxygen and com- paratively free from carbon dioxide. No ma Iter how pure the surrounding air may be, an individual may suffer from impure air in his lungs if by seden- tary habits, or other cause, his breathing becomes shallow and insufficient. Allowing sixteen as the average number of respira- tions per minute, with an air movement of twenty- seven cubic inches into and out of the lungs, the air respired in an hour would measure fifteen cubic fi et and in twenty-four hours 360 cubic feet, and with an output of 0.01 cubic foot of carbon dioxide per min- ute the respired air would contain four per. cent, of this gas. From these data may be calculated the amount of dilution needful to bring respired air back to a condition of purity approximating that of the free atmosphere. If fifteen cubic feet of breathed air containing 0.6 of a cubic foot, or four per ce of carbon dioxide, be uniformly mixed with ninety- nine times its bulk of air containing no carbon diox- ide, the 0.6 cubic foot of this gas present would constitute 0.04 per cent, of the mixture; but is using atmospheric air for the dilution the pereem of carbon dioxide in the resulting 1,500 cubic feet would be nearly 0.08, inasmuch as each cubic foot of REFERENCE HANDBOOK OF THE MI'.HK AT, SCIENCES Air the diluting air brings with it the 0.04 per cent, of this gas which ii naturally contains. Bui as the organic Taint in respired air which lias been diluted to this extent is perceptible by its odor to one entering from the fresh air. it is evident that this dilution is insuf- ficient Even when the carbon dioxide is diluted to 0.07 cent., sensitive nostrils can detect the presence of the associated organic matter; but if the 1,500 cubic feel containing 0.08 per cent, be further diluted with an equal volume of fresh air containing 0.04 per cent, of carbonic oxide, the mixture is reduced to O.Oti or six umes in 10,000 volumes of the air, and with this dilution of 3,000 cubic feet per hour per person, sanitarians are satisfied, except in the ease of certain hospitals. It is easier to pass 3,000 cubic feet of air without creating coldness or draughts through a large cubic space per man than through a small one. If a room only 300 cubic feet per man, its air has to be changed ten times in an hour to supply the 3,000 cubic feet of ventilation. If it give 1,000 cubic feet per man, the air has to be changed only three times. A linear inflow of less than two feet per second is lerceptible. With two feet of current air the area of the inflow to deliver the 3,000 cubic feet would Ixty square inches. The amount of carbon dioxide in a sample of air . termined by adding a known quantity of lime or baryta water to the air in a large glass bottle or jar, and' there after finding how much of the hydroxide has i converted into carbonate. The practical details 1 3 follows: Make an oxalic acid solution, lc.c. of which is equiva- lent to one milligram C0 2 . Make also a caustic baryta or lime solution of equivalent strength. Transfer the al- kaline solution for storage until required for use to small bot ties each holdingabout GO c.c.( two-ounce vials), each of which is corked securely and weighed, and the total ight of the bottle and its contents marked upon the 1. The air to be examined is collected in a clean perfectly dry glass bottle or narrow-mouthed jar, of known capacity. Ten liter bottles are large enough to give accurate results. A small bellows with a rubber tube on its nozzle is conveniently used in tilling the jar with the air to be examined, but care must be taken that the air entering by the valve of the bellows is not contaminated by any direct respiratory streams from individuals present. As soon as the change of air has been effected, one of the prepared baryta vials is uncorked and its contents poured into the jar, which is then closed by an ac- curately ground stopper, or preferably by a tightly fitting rubber cork. The baryta solution is then shaken in the jar, and made to flow all over its interior to promote its contact with the contained air; but to in- sure thorough absorption of the carbon dioxide the jar is usually permitted to stand until the following day before determining the loss of alkalinity. Meanwhile the volume of the air operated on is ascertained from observations made at the time the air was collected. The height of the barometer and of the dry and wet bulb thermometers or the dew point must be known, as well as the quantity of baryta solution in- troduced into the jar. The last is obtained by weighing the now empty vial in which it was stored and deduct- ing this weight from the gross weight marked on the label. The quantity in grams of the baryta solution employed must be deducted as cubic centime- ters from the known capacity of the jar. But in order that the experimental results may be suscepti- ble of comparison, it is necessary to express the air volume in the space which it would occupy when dry at 0° Centigrade and under a pressure of 760 millimeters of mercury. Increased pressure diminishes the volume of air, increased temperature expands it; and the pres- sure of the watery vapor present must also be taken into account. The temperature observations furnish the dew point, and through it, from the observations of Regnault, the pressure or tension of the aqueous vapor may be obtained. If \> repre ents this pressure, /, the temperature in Centigrade degrees, b the baro- metric height in millimeters, and V the capacity of the jar, minus the number of cubic centimeters of baryta solution introduced, the corrected volume will be equal to \ '--/>) 273 (273 I '(760 If the observations have been made on Fahren- heit's scale and in barometric inches the formula is: V(6-p)491 !».).!).' I1U . dt) in which dt is the number of degrees between 32° F. and the observed temperature. When baryta solution is used to absorb the carbon dioxide, the action may be considered completed in half an hour; but with lime water it is better to suspend further proceedings until next day. Then take, say, 20 c.c. from the jar, add phenolphthalein, and drop in the oxalic solution from a burette until the color is discharged. The loss of alkalinity in cubic centimeters = milligrams of CO., in the 20 c.c. of the solution tested, from which the *C0 2 absorbed by the whole of the baryta solution may be calculated = milligrams of CO, in the air collected. Convert weight of C0 2 into volume by multiplying by 0.573, and for purposes of comparison calculate it into volumes per 10,000 of the corrected air. It must be mentioned, however, that the volume of carbon dioxide found by this experiment is not all carbonic impurity, but includes that which is naturally present in the atmosphere. When the result of a contem- poraneous experiment on the external air has been deducted from it, the remainder will indicate the carbonic impurity or the carbon dioxide due to imperfect ventilation. An easily applied method of ascertaining whether a given air contains more than a certain number of volumes of carbon dioxide per 10,000 is based on the turbidity caused in lime water by the precipitated carbonate. If a half ounce of this liquid is shaken up in an eight-ounce vial filled with the air to be examined, the appearance of turbidity indicates the presence of eight or more volumes of carbon dioxide in 10,000 volumes of the air, and that the arrange- ments for ventilation in the apartments which fur- nished the air are not as satisfactory as could be wished. Bottles of various sizes are used by the operator conducting this, the household method of sanitary air analysis, and from the capacity of the bottle in which a just visible turbidity is produced the volumes of carbon dioxide per 10,000 become known. In another method, the minimetric, air is introduced in small quantity into a vial containing lime or baryta solution, which is well shaken, with gradual additions of the air, until the liquid shows a certain loss of transparency, when the carbon dipxide is calculated from the quantity of air needful to the production of this result. These, although pretty experiments, and described in full by most sanitary writers, have not come into general use, because they are not required. As they yield results which are only approximate, they can- not take the place of the accurate determination need- ful in a scientific inquiry, while, as rough-and-ready methods, their results convey no more information of practical value than may be gathered unpretentiously by the sense of smell. A well-ventilated room should not have more than one or two volumes per 10,000 in excess of the external air, equalling a total of five or six volumes. When the carbon dioxide amounts to seven volumes, a want of freshness is recognized on entering. When nine, ten, or more volumes are present, the organic odor becomes manifest. Although the carbon dioxide, as has been stated, is 163 Atr REFERENCE HANDBOOK OF THE MEDICAL SCIENCES generally accepted as a measure of the respiratory impurity, it is not an accurate one, for it is more readily diffused and carried off by ventilating currents than the organic exhalations which accompany it from the human system. Whence it comes that the continued occupancy of an apartment may give rise to organic odors in its atmosphere, although carbon dioxide may not be present in large quantity. The exhalation appears to adhere to walls and other surfaces, and textures, and to require time for its dissipation. But, while the carbon dioxide is not an accurate measure of the organic contamination in the air of occupied buildings, its estimation affords the best means of testing the efficiency of the ventilation. Sanitary inspectors do not recognize this fact. Sani- tary chemists have not brought it prominently into notice. When questions of ventilation are to be settled, Casella's air meter is used, and the air move- ment is calculated from its indications and the areas of inflow and exit. The inspector shows that so much air has entered or that so much has escaped, to be replaced of necessity by a corresponding volume of fresh air through the inflow ducts. But this is not enough. It must be shown that the air introduced has effected the purpose for which it was introduced. This may be done by a calculation based on the amount of carbonic impurity found by experiment. The capacity of the room must be ascertained, and in exact calculations deduction should be made for the body bulk of the occupants and for the furni- ture. The time during which the deterioration has been going on is another factor entering into the calculation. The carbonic evolution, 0.01 cubic foot per minute or 0.6 per hour per person, multiplied by the number of minutes or hours, gives the amount of the carbonic impurity expired. When this is divided by the carbonic impurity found by experiment in 10,000 volumes of the air, the quotient multiplied by 10,000 will express, in cubic feet, the volume of the air with which the respiratory products have been diluted. But, as the air volume in the room has contributed to the dilution, its capacity has to be deducted from the total to obtain the amount of the inflow. Thus if the data consist of twenty persons, three hours in a room having a capacity of 10,000 cubic feet, the air on analysis showing 14.5 volumes or a respiratory impurity of eleven volumes, as a parallel experiment on the external air indicates the presence of 3.5 volumes. 0.6 X20 X3 =36 cubic feet of carbon dioxide expired, 11 : 10,000 :: 36 : 32,727 cubic feet of air concerned in the dilution. 32,727-10,000 in room =22,727 inflow. 22, . 27 -j-3 =7,576 cubic feet inflow per hour. 75,76 -=-20 =379 cubic feet per hour per person. In practice it is often found that the inflow, as determined by the anemometer, is much greater than that obtained from the chemical results. That the air enters is certain, and that it fails to be utilized in diluting the expired air is equally so. In one of the schools of Washington, D. C, 800 cubic feet per min- ute entered the room, while but 324 cubic feet con- tributed to the ventilation. The cause in this instance was manifest. The temperature of the inflow was so great that the air rose immediately to the ceiling, whence it was drawn off by the lowered windows and foul-air flues. Impurities in Air. — Carbon dioxide in air, while essential to vegetable life, must be regarded as an accidental impurity in its relations to animal life when present in any locality in excess of that found in the free atmosphere. The sources from which the carbon dioxide is derived often yield with it other and more dangerous substances. These sources are, first, combustion for artificial warmth and lighting; second, the resolution or dissipation of dead organic matter, and, third, the resolution or dissipation of the tissues of living animals by the respiratory process. Products of imperfect oxidation are associated with the carbon dioxide from the combustion of fuel. A lamp or fire smokes and smells when its oxygen or air supply is insufficient. The smoke is unoxidized carbon and the smell an emanation from transition products. The dangerous product in the combustion of fuel is carbon monoxide (CO). This colorless and inodorous gas is highly poisonous, entering the blood and rendering the red corpuscles incapable of per- forming their functions even though pure air be afterward supplied. Death is the result of asphyxia. In rooms heated by stoves the headache, languor, and oppression occasionally produced are due to the escape of this with other gaseous products through the open stove doors, leaky joints, and turned dampers. Some experiments of St. Claire Deville and Troost indicated that the carbon mon- oxide might even pass through the pores of cast iron when the metal became strongly heated. The French Academy, therefore, caused an investigation to be made of this subject, and the conclusion was reached that this dangerous gas does pass through the metal when its temperature reaches a dark red heat. Since these experiments, air heated by furnaces or cast-iron stoves has been regarded as injurious. But doubt has been thrown upon the results of the French chemists by several later experimenters, and particularly by Professor Remsen, who has shown some possible sources of error, and who, having guarded against these, has concluded that, while carbon monoxide may be present in the air of furnace- heated rooms, it must exist in quantities so minute that it is questionable if it can act injuriously on the health of those who breathe it. The deadly nature of water gas as compared with coal gas is due to its larger proportion of carbon monoxide. Coal gas contains less than ten per cent., while water gas contains thirty to forty per cent. Water gas is manufactured by playing steam on glow- ing coke or charcoal, the products being carbon dioxide, carbon monoxide, and hydrogen. The num- ber of deaths from leakage of gas has been greatlj increased since the introduction of water gas. Where one death was formerly reported in a given time and population, there are now twenty-five to thirty deaths. Must of these deaths, however, are attributable to suicide rather than to accidental poisoning. In connection with local accumulations of these gases it should be remembered that they are explosive when mixed with air. It is therefore dangerous to strike a light in the room of a gas suicide or to look for a gas leak in a cellar or basement until after sonic ventilation has been effected. A mixture of one part gas to eight parts air is most violent in its explosion. With one to four there is not enough air for explosion, and with one to twelve there is not enough gas. The evolution of carbon dioxide into the air of a room during the combustion of illuminating gas or oil is generally underestimated in considering the carbonic impurity of occupied rooms. Parkes states that one cubic foot of gas consumed in an hour produces as much as the respiration of one person. One oil burner consuming four ounces of illuminating oil per hour was allowed in United States barracks for every ten soldiers. The oil consumed pervaded the barrack room with somewhat more carbon dioxide than was expired by the ten men. The necessity for increased ventilation must be considered with the presence of each lamp or gas jet. Associated with the carbon dioxide derived from the oxidation of the carbon of dead and decomposing organic matters on the surface of the earth, some- times aggregated locally into manure piles, cesspools, vaults, drains, and sewers, are certain compounds intermediate in composition between the complex or- ganic matter in process of putrefaction and the simply Kit REFERKNCK HANDBOOK OF THE MEDICAL SCIENCES Air constituted organic substances which arc the re ull of the completed oxidation. The sulphur present in certain tissues becomes converted into hydrogen or ammonium sulphide, while among the nitrogenous products are many foul-smelling and harmful gases . apors of an ammoniacal character; hydrocarbons also are formed. Formerly the reversion of organic matter to the inorganic condition was supposed to be due to I he purely chemical process of oxidation by I he oxygen of the air. Decomposition was regarded as a slow oxidation at a low temperature, as combustion was a rapid oxidation at a high temperature; but when Pasteur showed that meat could be preserved from putrefaction when exposed to the air, provided the air was first filtered through cotton wool, this chemical theory of decomposition had to be abandoned. Ultimately the saprophytic bacteria were discovered, :oid now these are recognized as so universally present and so essential to the disposal of organic matter that cannot be regarded as an impurity in the air. They arc the means to an end, one of the great links in the endless chain of life, and as important in the wonderful scheme of creation as the carbon dioxide which they prepare for the future growth of vegetation. The action of the sulphur gases on the animal system has been demonstrated experimentally by Barker on dogs and other small animals. Hydrogen sulphide produces vomiting and diarrhea, prostration and coma, which, like the effects of carbon monoxide, persist after removal from the contaminated atmos- phere. The exhaustion and coma continue, and death results if the impression fixed on the blood is suffi- ciently powerful. But, while this occurred in the subjects of Dr. Barker's experiments, it is well known that men may breathe with impunity for a time a sulphureted atmosphere many times stronger than those employed by him. Ammonium sulphide, irding to this experimenter, caused vomiting and febrile action, quickly followed by the development of a typhoid condition. Chronic poisoning by hydrogen sulphide manifests itself, according to some observations, by gradual prostration, emaciation, and anemia, with headache, foul tongue, anorexia, and the occasional eruption of boils, but it is not certain that these symptoms are due to this gas and not to organic vapors which accompany it. The action of the more complex organic vapors given off during decomposition has not been determined. The dogs subjected by Dr. Barker to cesspool air were all more or less affected, the symptoms being those of intestinal derangement with prostration, heat of surface, distaste for food, and those general signs which mark the milder forms of continued fever common to " the dirty and ill-ventilated homes of the lower classes of the community." But the sulphur compounds already mentioned contributed to these results. Even the constitution of these organic vapors is not known with certainty. Dr. Odling distilled half a gallon of the liquid contents of a cesspool until all volatile matters had come over. He treated the fetid ammoniacal distillate with hydrochloric acid, and afterward precipitated with platinum. The platino- chlorides of the organic alkalies were found to crystal- lize in well-defined, flattened, orange-colored tablets, evidently not the platinochloride of ammonium. Incineration of this platinum salt yielded 41.30 per cent, of the metal, while the platinoehlorides of ammonium, methylamine, and ethylamine gave respectively, 44.36, 41.04, and 39.40 per cent, of platinum. The salt formed from the carboammoniacal vapors was analogous in composition to that formed with methylamine. But inasmuch as the crystals were more like those of the ethyl salt, and as a mixture of the ethylamine and ammonium salts would corre- spond in percentage composition to that obtained from the distillate, he supposed that the sewage emana- tions were ammoniacal and ethylic. A sei'ies of experiments made by Smart showed that the volatile matters evolved during the fer- ment a 1 1 \ o changes in organic substances are of two different characters, the one vaporous ami ethylic, but not containing nitrogen if separated from the ammonia with which if is volatilized anil condensed, and the other volatile, carbonaceous, and solid, con- creting on distillation into white, soft, and grea v particles. The former has a dull, mawkish, not positively unpleasant odor, the latter a strong and intensely disagreeable smell. Marsh gas (Vll t ), a colorless, inodorous, and, fortun- ately, non-poisonous gas, is largely formed as a tran- sition product in the decomposition of vegetable mat ter. It is evolved in the gradual transformation of wood into coal, constituting in mines the "fire damp" which is the occasion of so many disastrous explosions. It explodes, in the presence of flame, when forming only one-eighteenth of the air of the mine. The re- sulting gases, carbon dioxide, nitrogen, and vapor of water, constitute the "after damp" or " choke damp" which suffocates those imners who have not been killed outright by the explosion. Associated with the carbon dioxide of respiration are certain organic exhalations which differ in con- stitution, according to the efficiency or imperfection of the oxidation in the tissues. In diseased condi- tions of the body these exhalations are thrown out in greater quantity than in health and the infection of clisease in some instances accompanies them. They are exhaled not only from the lungs, but also along with the perspiration from the pores of the skin. The quantity of organic matter thus eliminated has not been determined, but is known to be small. It does not diffuse like a gas into the atmosphere, but floats, when there are no currents to disturb it, like an odorous but invisible cloud. If evolved into the air of a close room its amount is proportioned to that of the carbon dioxide exhaled by the occupants, in the absence, of course, of any other output of this gas. As vapor of water is deposited from a saturated air, so these organic clouds become similarly condensed on walls, furniture, hangings, bedding, clothing, and other exposed articles. In a room saturated with organic exhalations the mere renewal of the air does not dissipate the taint, for the renewed air becomes immediately affected by the volatilization of the or- ganic deposits. The necessity for a thorough aeration is obvious. The evil effects of breathing respired air are at- tributed to these organic matters. Many experiments have been made on this subject, the most striking of which are those by Brown-Sequard and d'Arsonval, reported in 1SS9. They connected a series of four air-tight cages by means of rubber tubing and as- pirated a steady current of air through them. In each cage was a rabbit. The animal in the last cage of the series breathed the air which contained the respiratory products of the animals in the other cages, while the animal in the first cage was supplied with pure air. After a time the animal in the last cage died as a result of its confinement in the impure air, and a few hours later that in the cage next to the last also succumbed. The inmates of the first and sec- ond cages survived. On placing an absorption tube between the third and fourth cages, the animal in the last cage survived the experiment, while that in the third cage died. This seemed to indicate that the toxic substance in the air was destroyed by the sul- phuric acid and was therefore probably organic mat- ter. These experiments were repeated, with the same results, by Merkel in 1892. In a Smithsonian con- tribution, however, by Drs. Billings and .S. W. Mitch- ell, published in 1895, it is contended from some experiments made under their direction that in the air expired by healthy mice, rabbits, etc., there is no peculiar organic matter which is poisonous to the animals mentioned, or which tends to produce in 165 Air REFERENCE HANDBOOK OF THE MEDICAL SCIENCES them any special form of disease, and that it is very improbable that the minute quantity of organic mat- ter contained in the air expired from human lungs has any deleterious influence upon persons who inhale it in ordinary rooms. They concluded also that the discomfort produced by crowded, ill-ventilated rooms in persons not accustomed to them is not due to ex- cess of carbon doxide, nor to bacteria, nor in most cases to dusts of any kind, the two great causes of such dis- comfort being excessive temperature and unpleasant odors. These odors, it is said, may in part be due to volatile products of decomposition contained in the expired air of persons having decayed teeth, foul mouths, or certain disorders of the digestive appa- ratus, and they are due in part to volatile fatty acids given off with, or produced from, the excretions of the skin, and from clothing soiled with such excre- tions. They may produce nausea and other disagree- able sensations in specially susceptible persons, but most men soon become accustomed to them and cease to notice them, as they will do with regard to the odor of a smoking car or of a soap factory after they have been for some time in the place. There are no microorganisms in the air in the lungs. They are filtered out of the inspired air, or captured in mucus and ciliated out before they can reach the pulmonary cells. We know this to be the case be- cause when there is no break in the skin in an injury to the lung from a fractured rib, we may have em- physema and pneumothorax with hemorrhage, but no pleurisy. Besides this, Tyndall showed by the electric beam the freedom of the expired air from par- ticulate matter. But that evil consequences do follow overcrowding and its necessarily vitiated air is well known. Every schoolboy knows the history of the Black Hole of Cal- cutta. Evil consequences of a lighter grade are also recognized as the legitimate offspring of vitiated air. The breathing of air that has already been breathed gives rise in succession to feelings of languor and heaviness, headache, dulness of mind, drowsiness, dizziness and faintness, sometimes nausea and, if continued, feverishness. These symptoms indicate a poisoning of the blood by organic matters which would not be present in it with free supplies of air to wash them away. The brain is the first of the organs to feel the effects of the tainted blood. The mental in- aptitude of children after two or three hours in a close schoolroom is easily understood. The waste or- ganic matters retained in the blood are not necessarily absorbed from the contaminated air. They may be due in great part to a suppression of the regular exhalations and a consequent retention of matters which ought to have been exhaled. As with moisture in air, so with these organic exhalations. The air when saturated refuses to take up more. Again, their retention in the blood interferes with the oxida- tion which should go on in the tissues; and the transi- tion products that are formed, being also retained, add seriously to the disordered condition. The individual becomes poisoned by products of his own living processes. The human system, however, appears to accommo- date itself to a certain degree of impurity in the air, so that, after a time, the breathing of such air ceases to occasion the feelings of acute discomfort that have been mentioned. But in their stead a depressed con- dition of the system is developed, manifested by pal- lor of countenance and loss of appetite, strength, and spirits. The vitality of the individual is lessened. Every draught becomes dangerous to him, and even the chill from a wall or closed window may cause serious sickness. He becomes a ready victim to con- sumption if the germ of that disease is present, as is so frequently the case in the crowded dwellings of the poor in our large cities. Health, in fact, becomes broken and the nervous system prostrated, a condi- tion in which a resort to alcoholic stimulants often gives temporary relief at the expense of a more rapidly fatal issue. Besides the gases and vapors already mentioned there are many particulate bodies, living and dead organic and mineral, floating in the atmosphere. All are accidental and therefore impurities. More than thirty years ago, Professor Tyndall made use of an electric beam as a searchlight for floating particles. In pure air, made so by specially filtering it, the track of the ray is invisible, but in the free atmosphere it is defined with more or less brightness by reflection from particles ordinarily invisible. If the electric bean were passed through the air of many of our rooms, we would hesitate to inhale the aerial turbidity which it would reveal. The lower strata of the air are tilled with such impurities, but air at a height of 600 feet is comparatively pure in this respect. The smoke clouds, consisting of particles of unburned carbon which hover over manufacturing cities, seldom rise higher than this. It is impossible to do more than outline these float- ing particles in the most general way, because every- thing on the face of the earth is susceptible of being ground into dust and of being swept up by atmos- pheric currents. Matters, indeed, of an extraterres- trial origin are present in the form of dust derived from the destruction of meteors in their passage through the atmosphere. The inorganic dust con- sists chiefly of carbon particles, amorphous silicates, irregular fragments of hard mineral substances, and salts of calcium, potassium, sodium, and ammonium. The organic dust includes the detritus of decaying vegetation, starch cells, epidermal hairs, filaments from the pappus of the Composite, pollen grains, and disintegrated woody tissue. The animal kingdom al- so is represented in the dust by fibers of wool, plume- lets of feathers, butterfly scales, and other debris of insect life, together with occasionally epidermal and epithelial scales. Saprophytic bacteria are present, and in certain localities pathogenic bacteria as well. Locality and season influence the quantity and character of these impurities. Naturally air which blows over a long stretch of land contains more than sea air. Cotton is found in nearly every sample of autumnal air in the Southern States. Pollen grains, on many occasions, have given a yellow color to the rainfall. Autumnal catarrh, sometimes called hay fever, which affects so many people at a certain period of the year, is attributed by many to this impurity. Crystals of sodium chloride are notably present in the air of the seacoast, while in that of cities we find car- bon particles and crystals of ammonium sulphate from the combustion of coal. The air of houses contains fragments of the fibers of clothing and epidermal scales, while that of hospitals, workshops, factories and mines, etc., is charged with particles varying in character with the occupancy and work. Sometimes the inorganic matters pervade the at- mosphere of localities in the form of vapor, as in fac- tories where phosphorus or mercury is in constant use. The earliest observations on the impurities of air were made on condensations gathered from the outside of a vessel containing ice. Subsequently experiments were made on water which had been shaken with suc- cessive volumes of air. In both cases a liquid was obtained which putrefied readily and in which the presence of living organisms could be identified. R. A. Smith was perhaps the first to use the latter method. He put 150 drops of pure water in a small vial containing air from a cow stable. He shook the bottle that the water might entangle and wash out all particles of solid matter from the air. He renewed the air; and this he did 500 times. When he examined the water under the microscope, he was astonished at the immense number of spores which were visible, along with many other matins organic and mineral: ami afterward many animalcules of various kinds were developed in it. 166 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Air At the present time aerial organic matter is investi- i,.,] microscopically, biologically, and chemically. ■Jolid particles for microscopic study arc caught on a r|ass slide lightly coated with glycerin. The general ractcrs of atmospheric impurities may be ascer- tained by an examination of I lie rain or snow, for all e impurities that arc not dissolved or absorbed by lie rain are washed down by it. But for evaporation, lensation, and rainfall, the inhabitants of the h would speedily be stifled in the dust swept up mi' atmospheric currents. Distant objects, hazy ,ud indistinct in a dry summer air, become sharply lUtlined in a purified rain-washed atmosphere. In water suspended impurities may be seen with the laked eye, and in the gradual melting of a pure white nantle of snow the stain made by its entangled im- mrities will appear before it has shrunk to half its iriginal thickness. The biological examination resolves itself into a letermination of the number of bacterial colonies and ither microorganisms in a given volume of the air. \ith culture experiments for the study of species. Official observations at the Montsouris Observatory tear Paris. Trance, have shown that there are few lacteria in the air in winter, and that the numbers acrease through spring and summer to over 100 cubic meter in the autumn. The air of city I - is densely charged with bacteria. The atmos- phere is purer in this respect in its upper strata: tir collected at over 6.000 feet is practically free rom bacteria and moulds. Chemistry has done but little to perfect the organic inalysis of air. With known methods of analysis the I s obtained by the expenditure of much time and ■are are of small value. If an air specimen contains tit unusual amount of the organic elements, it may be orrectly considered as impure, but the nature of the mpurity is not denned. The carbon estimated may ■ been a harmless particle of soot, or in part it may lave been essential to the spread of a deadly disease. Nevertheless, analyses are made as a matter of official routine by sanitary officers in England and France. The organic substances are absorbed by aspirating arge volumes of the air through a small volume of listilled water, and the liquid menstruum is then inves- tigated by the processes of water analysis. Professor Remsen endeavored to improve on this process by Altering the air through powdered and moistened pumice before passing it in fine bubbles through the distilled water. He thus showed that, so far as could be determined by chemical means, all nitrogenous aiatter was retained by the filter. But, as germs or microscopic organisms might have passed through without thus showing their presence in the absorbing liquid, owing to the necessarily minute trace of nitro- gen in them, Smart carried out a series of experiments which determined, first, that the nitrogenous matter of air, excluding ammonia from consideration, is particulate; second, that it consists in large part of microorganisms; and third, that filtration through Austrian glass wool effects their removal from the passing air. The experiments were conducted in a sterilized apparatus. The air was drawn through a short glass tube one centimeter in diameter, lightly packed for two or three inches of its length with the glass wool. From this it was passed in fine division through distilled water. After this it was mixed with steam generated from a dilute solution of alkaline po- tassium permanganate, the mixture immediately enter- ing the tube of a Liebig's condenser, where the steam was deposited, carrying down with it, after nature's process of air purification by the rainfall, any micro- organisms which might have escaped removal by lilt ration or absorption. The difficulties in the way of sterilizing the various parts of this apparatus were such that the first experiments, which gave speedy developments in culture liquids tainted by the filter, the absorbing liquid, and the condensate, were re- garded only as the practical expression of these diffi- culties. The experiments we; I with precau- tions. suggested as necessary by the previous experience, and ultimately success attended them. One of the processes of water analysis to which these matters were subjected involved the distillation of the ammonia, which was present in the liquid, and its estimation by the calorimetric method with Nessler's solution. Ammonia gives, with this test solution, a faint straw-yellow color, which deepens, in proportion to the amount of ammonia present, to a dark sherry brown, or to a dark haziness or distinct precipitate. But it not infrequently happened that in testing for ammonia in the distillate from the pure water in which the glass wool containing the organic matter of the air was suspended, as well as in that from the absorbing liquid which contained most of the ammonia, and in that from the condensate which contained but a trace, a citron-green color was produced which masked the ammonia reaction and rendered its estimation impossible. Dr. Kidder, of the navy, observed this interference with the ammonia coloration, and attrib- uted it to the presence of substances evolved in the putrefaction of organic matter. He concluded from the few experiments he made that the amines are not necessarily concerned in its production, as he found that butyric acid gave a somewhat similar interference to that met with in the experiments on air washings. But the haziness with which the presence of butyric acid masks the true ammonia color is not the citron- green coloration which so frequently occurs in the analysis of foul airs. This is due to the presence of an ethyl compound which is given off from the carbo- hydrates while undergoing change. It may be ob- tained free from the ammonia which ordinarily accom- panies it and obscures its reaction by submitting the liquid containing both to the process of nitrification. It may also be obtained from ammonia and free glu- cose, and from starch, cane sugar, tannin, salicin, etc., after treatment with heat and acids. In some of the experiments referred to, an air volume of 100 liters was passed through the interior of a glass globe which contained liquid sewage and silt, garbage, or other foul and decomposing materials, and then through the glass-wool filter, absorber, and condenser to remove the matters with which it had become contaminated. Culture experiments showed the satisfactory removal by the filter of all germs and nitrogenous matters, ammonia excepted, and chem- ical tests determined approximately the quantity of organic matter thus removed. In some instances a second air volume of 100 liters was drawn over the organic matter in the globe, and the results obtained from the filter through which it was afterward passed did not differ from those of the first experiment on the same organic matter. From these experiments the conclusion appears admissible that the volume of air which is contaminated by a certain decomposing organic mass is the volume which comes in contact with it. If no air is drawn through the foul globe, only that which is contained in it is rendered impure. This air has its oxygen in time replaced by the foul- smelling gases of decomposition. Evaporation takes place from the contained liquid until the stagnant and enclosed air becomes saturated. The ascensional force of evaporation carries from the smeared and half-dried sides of the globe, and from the unsub- merged solids within it, some of the innumerable mi- croorganisms with which they are pervaded, and the air becomes charged with organic particles to an ex- tent proportioned to its temperature and hygrometric condition. If a volume of air is drawn through the globe, it will be contaminated by organic matters carried away by its own movement and by the in- creased activity of evaporation produced by it. If a second volume is drawn through, it will be con- taminated in like manner, and to the same extent, if the volume, rapidity of passage, temperature, and 167 Air REFERENCE HANDBOOK OF THE MEDICAL SCIENCES hygrometric condition are the same in both instances; and so for a third, a fourth, or more volumes, until the decomposing mass has become changed by their agency. This is recognized practically in sanitary work. The dead are buried that their decomposition may not contaminate the atmosphere. For the same reason garbage is collected and removed. A recep- tacle for foul-smelling and fermenting matter is less of a nuisance and less dangerous to health when fitted with an air-tight cover than when freely exposed to the air, for in the latter case every volume of air which comes in contact with it is a volume of air polluted. Sanitary officials in growing cities protest against the continued existence of small surface streams which of necessity pass into the condition of open sewers, taint- ing every volume of air which comes in contact with their foulness. These are bricked over and the air is preserved from the impure contact. But in the con- struction of regular systems of sewerage provision is made for this contact under the name of ventilation. The sewers are tapped at regular intervals along the streets for the exit of the contaminated air. From the present point of view this ventilation of the sewers is of questionable benefit. The volume of air rendered impure, and possibly dangerous, is proportioned to the thoroughness of the ventilation. Sulphureted gases may be diluted, and the outflowing air be free from disagreeable odors, but the very air movement which effects this may raise invisible clouds of fermentative and morbific agencies from the foul interior. Ex- periments on this point would be of value. Those mentioned above indicate that the communication with the outer air should be only such as is needful to relieve tension and prevent the forcing of seals, and that these air holes should be guarded by some filtering material. But since the volume of air which becomes contaminated is that which comes in contact with the fermenting material, it may be reduced as well by diminishing the extent of the impure surface as by cutting off the ventilation. Hence sewers of small size, as in what is known as the separate system, are to be preferred, on sanitary grounds, to the large ramifying tunnels of the combined system. The foul airs which arise from sewer apertures are matters of every-day observation. If well diluted with air they may not affect the sense of smell, but they rise, never- theless, from the grated covers on our streets, and may be seen, by the vapor precipitated from them, as an uprising column in weather which clouds the air of respiration thrown out from the lungs. With open streets and lively breezes it is probable that these exhalations are dissipated, or rather diluted, to harmlessness, but in enclosed spaces and stagnant atmospheres the sewer air, which is so carefully ex- cluded from living rooms by intelligent plumbing, may enter as fresh air through open windows and apertures specially devised for its admission. _ Sewer air is atmospheric air with its oxygen dimin- ished and its carbon dioxide increased to from ten to fifty volumes per 10,000, and with taints or not- able amounts of marsh gas, hydrogen sulphide, am- monium sulphide, and amines or compound am- monias in which one or more atoms of hydrogen are replaced by a positive radicle, methyl, ethyl, amyl, etc. Cesspool air has an excess of these foul-smelling constituents, for the contents of a cesspool continue to putrefy, while the sewage in a well-constructed system of sewerage should be carried away before putrefaction sets in. Each of the impurities in sewer air is harmful when breathed in strength, but not specially dangerous when diluted with atmos- pheric air, for it is well known that men whose occu- pations bring them into contact with this contaminated air do not suffer specially from disease. But sewer air may be a cause of diarrhea or other gastrointestinal disturbance; also, general depression or ill health, and anemia may be due to the same cause. It is believed by some that other infectious diseases may be ac- quired from exposure to sewer air, provided always that the necessary causative bacteria are present therein. The air of dwellings is sometimes contaminated with ground or cellar air drawn up through a porous soil by the greater warmth of the living rooms. Ground air contains more carbon dioxide in summer than in winter on account of the influence of heat in promoting decomposition of organic matters in the soil. In general terms it contains in summer more and in winter less than one per cent, of this gas, or 100 volumes in 10,000 of the air; it may also be contaminated by other products of decomposition. Hence may be inferred the inadvisability of furnish- ing cellar air or air introduced by tunnels into a build- ing for purposes of ventilation. This applies in par- ticular to buildings erected on made ground. In fact, cellars, in default of an impermeable lining, should have a free circulation of air separate from the venti- lation system of the superimposed building. Charles Smart. R. J. E. Scott. Air Embolism. — See Embolism. Airol. — Airoform, bismuth iodosubgallate, bis- muth oxyiodosubgallate, C H 2 (OH),CO 2 Bi(OH)I. It is prepared by heating equivalent amounts of bis- muth subgallate and hydriodic acid, or of freshly precipitated bismuth oxyiodide and gallic acid, in water. It is a graj'ish or greenish, light, odorless and tasteless powder, insoluble in water or alcohol, but soluble in mineral acids and weak alkaline solutions. When exposed to the air it gradually takes on a red color. It is employed as a substitute for iodoform in the treatment of wounds, ulcers, burns, etc., in powder, in ten-per-cent. ointment, or in ten-per-cent. suspension in glycerin and water. The best oint- ment base for airol is a mixture of seven parts of anhydrous adeps lanse and two parts of petrolatum. Air Passages, Foreign Bodies in the. — Nose. — The presence of foreign bodies in the nose is of common occurrence. The list of them comprises extraneous substances introduced either through accident or, in the case of infants or of insane adults, by design; sequestra of diseased bone; and parasites. They may also enter the nasal cavities from behind, during the act of vomiting or of choking, or in paralysis of the soft palate. Rarely, as in gunshot wound, they may pass through the walls of the nasal cavity from with- out; an erratic tooth may enter the cavity from below. The history of those of the first variety is usually as follows: A child of about two, old enough to creep but not sufficiently intelligent to know better, thrusts some small, rounded object, such as a bean or a shoe- button, which it has found upon the floor, into its nostril. If the child be not caught in the act the body may escape immediate detection. Soon symp- toms of chronic inflammation are established. These are confined to the nostril in which the body is, and continue until it is removed, the irritation often being severe and the discharge exceedingly fetid. The mucous membrane adjacent to the foreign bod; is in a condition of superficial erosion. The body, if too firmly impacted to be dislodged by simply blowing the nose, remains fixed, usually in the in- ferior meatus, until removed by the surgeon. Removal should be attempted by means of a hooked probe or fine forceps, the sensitiveness of the nasal cavity being borne in mind, and the removal of the body carefully effected after thorough cleansing of the cavity "has been effected and local anesthesia has been obtained, either by cocaine or by suprarenal extract. In the case of nervous children general anes- thesia is desirable. Copious hemorrhage, lasting two or three minutes, often follows, but is generally of little 168 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Air Passacps, Foreign bodies In moment. The nostril should be washed several limes a day with a weak disinfectant. In four or five days the membrane will often have healed so com- pletely that no trace of the trouble can be seen; the discharge ceases entirely, and the cure is complete. The possibility of the presence of a foreign body in all cases of fetid discharge confined to one nostril should always he remembered, and, tin 1 nostril having I n cleansed with a warm douche, careful examination should be made with speculum and probe. If l lie object be lodged far backward, care should be taken in removing it not to allow it to fall into the larynx Fig. 62. — Lead Collar-button in the Right Bronchus of a Lad of Eighteen Years; removed by upper bronchoscopy by Dr. Chevalier Jackson. The writer has seen a case in which a button intro- duced during infancy remained undiscovered in the nose for thirty-two years. Rhinoliths are merely calculi formed by an accu- mulation of the earthy salts of the nasal secretions around some foreign body or inspissated mucus. Their presence has given rise to such irritation that they have been mistaken for cancer. Careful examination and the history of the case will easily establish the diagnosis. If the concretion be too large to be readily removed it should first be crushed. Foreign bodies of this nature are rarely met with, although one is reported which weighed 720 grains. Sequestra of bone, particularly in tertiary syphilis, sometimes re- main in the nasal cavity after their separation, tints acting as foreign bodies. They must be thoroughly removed preliminary to further local treatment. Parasites. — In tropical countries, seldom elsewhere, various kinds of flies, of the order Muscidoe, may enter the nasal cavity, preferably of a patient suf- fering from catarrh, and there deposit eggs. These are quickly hatched, causing in succession irrita- bility, tickling, and sneezing; later, formication, bloody discharges and epistaxis, with edema of the face, eyelids, and palate; excruciating pain, generally frontal; insomnia, and if the condition be unrelieved, convulsions, coma, and death. Sometimes the larva? are sneezed out, or may be seen on examination of the parts. This will, of course, establish the diag- nosis. Destruction caused by the larvae may extend to the mucous membrane, the cartilages, and even the bones of the head, the ethmoid, sphenoid, and palate bones having been found carious. Where the maggots have entered the frontal sinus or the antrum of Highmore, injections of tobacco or alum, or insufflations of calomel, formerly used, will be of little avail. Chloroform or ether, preferably the former, either inhaled or driven into the nasal recesses in I he form of spray, is the sovereign remedy, as under it the larva' are not killed, to remain in situ and thus cause further trouble, but escape with all haste to tin; outer air. Meanwhile, anodynes should be given to allay pain, and the patient's strength should be carefully sustained. Such measures, however, are serviceable only when tin' ease i,^ seen early and the Larvae are si ill upon the surface of the mucous mem- brane. When they have attained their full develop- ment they burrow into the soft tissues, whence it seems impossible lo extract them except by Seizing them bodily and dragging them out. If the desper- ate character of the situation in severe cases of this kind, and the impossibility of reaching the seat of irritation through the natural passages are taken into consideration, no surgical procedure which promises relief can be thought too severe. It is therefore jus- tifiable to open into the antrum or the frontal sinuses from without, to perform Rouge's operation, in order to gain access to the upper part of the nasal cavities, or to open freely into the ethmoid cells. Several cases in which the patient's life has thus been saved have been related to the writer in recent years. Leeches, ascarides, earwigs, and centipedes have been found in the nose, causing insomnia, frontal pain, sanious discharge from the nose, lacrymation, vomiting, and, in some cases, great cerebral excite- ment. Sternutatories are generally sufficient for their expulsion. Tonsils. — Three general varieties of foreign bodies may be found in the tonsil: (1) Foreign bodies proper, or substances which have become lodged in the tonsil during deglutition; (2) tonsillary concretions or calculi; (3) parasites. The last two conditions are not common; the first will be described under Foreign Bodies in the Pharynx. Tonsillary calculi are formed in the lacunae of a chronically inflamed tonsil by a perverted condition of the natural secretions and their retention in the recess through closure of its outlet. They vary in size, seldom attaining a greater diameter than three- fourths of an inch, and consist of phosphate and car- bonate of lime, some iron, soda, and potassa, with varying proportions of mucus and water. Hence they are not necessarily of gouty origin. The symptoms, generally not prominent, may be slight pricking of the throat with, occasionally, dysphagia. The presence of the calculus is sometimes directly irritating, and may give rise to quinsy, ulceration of the cavity, and abscess. Frequently, however, the symptoms are reflex in character. This is especially true with relation to the ear, in which organ the existence of a tonsillary calculus may be associated with various forms of otic congestion and with tinnitus. Diagnosis, by ocular examination or by the use of the probe, is usually easy, and so also is the removal of the calculus by means of a forceps. Sometimes, however, the mass is so completely covered that it is only seen after careful exploration with the probe or even after the actual removal of the tonsil. In most cases the latter operation will afford the most certain cure. Very rarely, hydatids and trichoceph- ali have been found in the tonsil. Pharynx. — Foreign bodies are often arrested in the pharynx, and the variety of these bodies is great. Certain individuals seem especially liable to this accident, either from carelessness in eating, from insensibility of the parts, or from some unusual irregu- larity in the pharyngeal walls. Foreign bodies of large size generally lodge in the lower part of the cavity, where the cricoid and arytenoid cartilages project backward, or between the base of the tongue and the epiglottis. Small and sharp-pointed bodies may 169 Air Passages, foreign IJodics in REFERENCE HANDBOOK OF THE MEDICAL SCIENCES become fixed at any part of the pharynx, particu- larly in the tonsils, on account of their exposed posi- tion and the irregularity of their surface. They may also be entangled in the pillars of the velum, or in the lateral folds of the cavity. A large body may be found stretching across the whole width of the pharynx. Symptoms. — These are local pain, dysphagia, and more or less inflammation, with occasionally ulcera- ion or abscess of the pharynx; but generally there is simply localized inflammation and irritation. If an abscess be formed, the foreign body may escape through a fistulous opening in the neck, or it may perforate some important blood-vessel, or may even penetrate the intervertebral substance and cause caries of the vertebral bodies. Fig. 63. — Outer Tube of a Tracheal Cannula, inhaled and lodged in the left bronchus in a man of thirty-five years, upon whom tracheotomy for larryngeal carcinoma had been performed; tube removed by bronchoscopy through the tracheal wound by Dr. Thomas R. French. Inflammation of the pharynx may give rise to dysp- nea, while a large foreign body may cause suffoca- tion by obstructing the entrance to the larynx. The diagnosis can generally be established by the history of the case and by inspection of the pharynx. In cases presenting unusual difficulty the diagnosis may be established by the use of radiography. Nervous patients often insist upon the presence of a foreign body in the throat despite all assurances to the contrary, particularly if the pharynx be sensitive, or if at a certain point there is an inflamed lymph gland, or if, as often happens, a hard substance may have caused a slight laceration of the mucous mem- brane while being swallowed. Treatment. — The patient's tongue should be well depressed, and the upper parts of the pharynx carefully examined in a strong light. If the foreign body does not then appear, search should be made fin- it with the aid of the laryngoscope in the region of th ■ base of the tongue, the glossoepiglottic and pyra-* form sinuses, and the upper portion of the larynx. If present, it will generally be found without much diffi- culty, and should be removed by the finger or by a suitable forceps or probang. Local anesthetization of the pharynx will greatly assist in the diagnosis and treatment of these cases. If dyspnea be urgent, immediate surgical interference, of a nature suited to the special features of the case — either tracheot- omy, thyrotomy, or, possibly, some form of sub- hyoidean pharyngotomy — may be required. The sensations of the patient are often unreliable, and the feeling of irritation caused by the presence of the body may continue for a long while after its removal. This may be relieved by swallowing small lumps of ice, and later, if necessary, by the application of as- tringents and, in some cases, by galvanism. Larynx. — By reason of the danger to life which attends the lodgment of a foreign body in the larynx, this condition becomes one of the most important in surgery. The variety of objects found is infinite, and may be thus divided: Alimentary matters, introduced during mastication in the act of laughing or talking, in deglutition, or in inspiration during vomiting; metallic bodies, such as coins, buttons, puff-darts, etc.; teeth, artificial or natural; necrosed bone from neighboring regions, as from the nose in tertiary syphilis; and fragments of the laryngeal cartilages themselves, as thrown off in the Tate stages of syphilis, tuberculosis, and cancer of the larynx. Foreign bodies in the trachea may pass upward and become impacted in the larynx; and, rarely, they may gain access to the larynx directly from without, by forcible penetration of its walls, as in the case of bullets. Again, the epiglottis may become incarcerated in the larynx, or occlusion may take place from the so-called swallowing of the tongue. The symptoms vary with the size and position of the object. Thus a large body fixed in the rinia glottidis may, unless dislodged, cause almost instant death. Again, small bodies lodged in out-of-the-way corners may remain indefinitely, causing nothing more than cough and discomfort. Dyspnea may occur days after the entrance of a foreign body, from inflammation and tumefaction of the soft parts of the larynx, and danger from the presence of a foreign body may suddenly become imminent from alteration in its position. Great peril sometimes arises from violent spasm of the glottis, due to irritation caused by the foreign body. Mental anxiety and localized pain are prominent symptoms in cases in which the accident does not immediately threaten life, but is followed by inflammation which rapidly becomes active. The diagnosis is established by the history of the case, verified or otherwise by laryngoscopic exami- nation or by radiography. The greatest difficulties arise with children too young to express themselves, in whom pain in the throat and symptoms resem- bling croup will often be the only indications ob- tainable. Here the use of the laryn-gosope, or direct inspection of the larynx as practised by Kirstein and his later followers, or radiograph}', will be in- dispensable. A cautious prognosis must be given, even after removal of the body, as long as there are any symptoms of local inflammation. Treatment. — The offending body should, of course, be at once removed; if possible, through the natural passages and by means of the laryngeal forceps, aided by the laryngoscope, in case the symptoms are not urgent. Removal may be facilitated by placing the patient on his back upon a table, with the head hanging over the edge of the table, in which position breathing is easier and the law of gravitation becomes directly helpful. If asphyxia threaten, tracheotomy should be done at once and the foreign body after- ward extracted as described above. Bodies which at first are immovable may sometimes bo loosened by reducing the local inflammation. In rare cases, when 170 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Air Passages, r»>ri*iKn Bodies In the object has become firmly impacted, thyrotomy become necessary. A case is recorded in which : , oeedle, transfixed in the larynx, was pushed through the anterior laryngeal wall, and thus removed. Trachea and Bronchi. — Any object which can pass through the rima glottidis may, of course, find [ts way into the trachea, in the same manner as was ribed in the paragraph relating to foreign bodies in the larynx. Sharp objects lodged in the esophagus, and even diseased bronchial glands, may work their way through the walls of the trachea, and into its cavity. It sometimes has happened, through careless- Mi' by accident, that parts of instruments used in Fig. 61. — Glass-headed Pin in the Left Bronchus of a Child [Vo-and-a-half Years; removed by upper bronchoscopy by Dr. Chevalier Jackson. intralaryngeal operations, tracheal cannula?, laryngeal brushes, and even bits of solid nitrate of silver, have dropped into the trachea. If too large to enter either main bronchus the body will probably remain at the bifurcation. Otherwise it will pass into one bronchus or the other, preferably the right, on account of its anatomical position, in the proportion of five to three, and thence travel indefinitely into one of the more remote bronchial divisions. Asphyxia may also be caused by the entrance of water into the trachea, of blood during a surgical operation, of pus from the bursting of an abscess, of vomited matter, or of liquid food. The symptoms will depend upon the nature of the body and its exact location in the lung. Small objects have remained encapsulated for years withoul causing discomfort or serious results. Smooth, rounded bodies irritate less than irregular ones. Inflamma- tion of the lungs from a foreign body may occur, and at the same time the presence of such a body may be entirely unknown. Large objects and fluids may eau e death by instanf suffocation, or death may re nil in the eour-e of a few minutes, the symptoms pre 'Midi being urgent e not speedily afforded, death, with all the signs of asphyxia, soon follows. Severe dyspnea, fol- lowed by relief without extrusion of the foreign body, indicates thai the body has probably dropped from the larynx into the trachea. Dyspnea is. of course, more urgent when the trachea i- occluded than when the foreign body stops only one bronchus. Physical signs due to the presence of a foreign body in the lung may be altogether wanting, but they are gener- ally more or less distinct. They are the following: whis- tling or flapping sounds at the point of lodgment, decreased fremitus, and absence of respiratory murmur in the lung beyond. The body may change its posi- tion, passing from one bronchus to that of the opposite side. A body, small when swallowed, may become more dangerous through increase in size, either by imbibition of water or by forming the nucleus of a concretion. If, however, a hollow, cylindrical body, such as one of the parts of a tracheotomy tube has found lodgment in the bronchus, little resistance may be offered to the passage of the air, no advent it ions sounds created, and no obstruction caused in the lung area beyond. In such a case diagnosis by ordinary means might be impossible. At or about the bifurcation the body may be seen with the laryn- goscope. While the laryngoscope may fail to reveal the presence of the foreign body in the trachea, it can at least furnish satisfactory evidence that the object in question is not located in the larynx. The lodgment of a foreign body in the lung may result in pneumonia, tuberculosis, abscess, or gangrene. Or it may become encapsulated and do no apparent harm. Rarely a body, in several recorded cases an ear of barley or other grain, having formed an abscess of the lung, has been discharged through the wall of the thorax, with complete recovery. Diagnosis. — The fact that some foreign body has been inhaled should be established, if possible, and the site of the body determined. In children and incompetents, and in cases in which the dyspnea is urgent, this may not be easy. In addition to the diagnostic aids already mentioned there are two which, in comparatively recent years, have revolutionized this whole subject, turning dark- ness into light and affording almost certain relief, when formerly the life of the patient was generally sacrificed. The first of these is radiography, the efficiency of which in cases of a foreign body in the bronchus has proved it one of the most valuable contributions to science of modern times. By means of this admirable method it is possible to determine with almost mathematical certainty the precise location in the lung of the object inhaled, as well as its shape, its size, and its special characteristics. These details of information become invaluable when the extraction of the object is attempted, as they en- able the operator to determine what particular methods and what special instruments may best be suited to the case. Thus, for example, the procedure for the extraction of a closed safety pin of small size would be far more simple than the measures called for in the removal of a safety pin of large size, open, and lodged in the bronchus point uppermost. The prognosis is serious; it depends upon the nature of the foreign body, the amount of dyspnea, and the organic lesions which may result. The danger is greatest at the first, and although it diminishes in varying degree as time passes, it is never entirely absent. Even after expulsion of the foreign body death may occur from the organic disease set up. The expulsion of one object does not, especially with 171 Air Passages, Foreign Bodies in REFERENCE HANDBOOK OF THE MEDICAL SCIENCES children, preclude the possibility of others remaining in the lung. Treatment. — The treatment of foreign bodies in the trachea must be determined by the circumstances of the case and by the nature of the foreign body. When the trachea and bronchi are filled with fluid the patient should be placed upon his back, the head and shoulders as low as possible, the mouth should be forced open, the tongue drawn far forward, and the walls of the chest compressed. Artificial respiration should be instituted the moment the trachea is suf- ficiently free to allow of the ingress of air. The treatment of solid bodies which have gained access to the trachea or bronchi has been until re- cently one of the most difficult problems of surgery. Fig. 65. — Brass Paper-fastener in the Right Bronchus of a Woman, Twenty-three Years old; removed by upper bronchoscopy by Dr. Chevalier Jackson. With the advent of bronchoscopy many of the dan- g3rs attending it have been overcome and many lives saved. Thus far, however, the technical diffi- culties in the application of the bronchoscope have caused its use to be confined to a comparatively few experts. Occasion may arise, therefore, when its aid may not be attainable. In view of this, it may be well to rehearse the measures hitherto employed. In general two plans have been pursued. One, an ex- pectant treatment in which spontaneous expulsion of the foreign body has been hoped for. Failing in this, surgical measures have been resorted to. Of the lat ter the most common has been the performance of a low tracheotomy. Analysis of large numbers of cases treated by the older methods shows that if the object inhaled has been small in size, regular in contour, and of a smooth surface, better results have been obtained by waiting for spontaneous expulsion than through operation. Thus Roe, of Rochester, N. Y., in a notable contri- bution to the subject, in which more than 500 cases of all kinds were studied, reported that in cases oper- ated upon seventy-eight per cent, recovered. Of all not operated upon, including the cases in which death from suffocation followed the inhalation of the object t |uickly for any operative aid to have been offered, seventy-three per cent, recovered. Operations by which the chest wall was nsected and entrance made into the substance of the lung have almost invariably proved fatal. It will thus be seen that surgery in these cases has met with little success. The most practical method has been the performance of a low tracheotomy. Through the opening thus obtained it was hoped that the foreign body might be expelled by the act of coughing. Failing in this, attempts were made to recover it by the aid of suitably constructed forceps. In cases where this could not be accomplished it was recommended that the edges of the wound in the trachea be kept apart, if necessary, for several days, in order to facilitate the expulsion of the foreign body should it become dislodged and coughed up- ward toward the surface of the body. Where such measures are pursued it is important that the pi tion of the patient should be considered. If possible, he should be caused to lie with the head and shoulders lower than the rest of the body. Thus the pid of gravitation may be secured and the tendency of the body to fall backward, after efforts at coughing which have driven it upward, will be overcome. Mild sedatives may also be indicated. The admin- istration of belladonna to lessen the bronchial secre- tions, as long ago recommended by the writer in general operations in the region of the larynx and trachea, is useful. Morphin may also be used. Swain suggests the hydrobromate of hyoscine as an adjuvant to morphin. The conditions demanding speedy operation are: 1. Urgent and dangerous symptoms, as progressive dyspnea, or frequently occurring attacks of dysp- nea or laryngeal spasm, when laryngoscopic exami- nation fails to reveal the object or shows that its speedy removal by the natural passages is impos- sible. 2. When a sharp and irregular body is im- pacted, as shown by the laryngoscope, in such a way that immediate extraction is impossible, and when acute inflammation, and especially edema, are rap- idly developing, as evinced by increasing dj'spnea. 3. In the case of a foreign body of any nature which lies loosely in the trachea, and the movements of which excite laryngeal spasm or coughing of dan- gerous violence. 4. In the case of a foreign body which is impacted in either of the primary bronchi, as ascertained by the rational and physical signs, particularly by auscultation. In this latter condition low tracheotomy and immediate direct attempts at extraction are often successful. Direct examination of the site, and demonstration of the foreign body in or at the mouth of a bronchus, by means of the fin- ger introduced quickly into the trachea, are possible, and this knowledge renders the subsequent instru- mental removal of the body more easy. The entrance of a foreign body into a bronchus to such a distance as to place it beyond reach through the natural pas- sages, is an accident of the gravest danger. A num- ber of cases have occurred of late years in which sur- gical operation has been attempted by entering the bronchus through the chest wall from without. All have proved fatal. 5. Sharp-pointed, hard, and irregular bodies within the air passages will, as a rule, demand bronchotomy, provided they are not so located that they may be reached and removed by the natural passages at an early moment. The plan of treatment by inversion of the patient has of late years fallen into disrepute, and should seldom be practised, unless tracheotomy can be done at once if required. In employing it, it should be remembered that the supine position will favor exit of the body, particularly if the glottis be in the condition of deep inspiration. In all cases the diagnostic importance of a thorough laryngoscopic examination cannot be too strongly insisted upon. The development of the method known as bronchos- copy has effected a revolution in this department, as to diagnosis, prognosis, and treatment. To the genius of the late Joseph O'Dwyer of New York is due the first suggestion bearing upon the subject. Among other modifications of his intubation tubes O'Dwyer devised one especially intended for the expulsion of foreign bodies from the trachea. This 172 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aix-la-Chapelle • ibe was of the largesl possible inner caliber, with hii walls, almost straight in its long diameter and lung enough to extend well into tlie trachea. Through ii loose bodies of relatively small size may be coughed out. This tube is especially adapted for small children. UgernOll Coolidge of Boston demonstrated the cticability of passing a long tube through the cervical wound and down the trachea in a tra- oheotomized patient, and of then illuminating by means of a head mirror the parts of the trachea below the distal end of the tube. By this means ign bodies could be searched for in the more ote parts of the bronchial tract. Later. Kirstein lit the method of direct laryngoscopy. Finally, bining the suggestion of O'Dwyer that a long could 1"' passed into the trachea through the larynx, with the suggestion of Coolidge that by means strong light the deeper bronchial tract could be ifactorily illuminated, Killian of Freiburg modified the instrument of Kirstein in such a manner as to produce the bronchoscope, an instrument which, nidified by Chevalier Jackson of Pittsburg Pa., ns to have reached a stage of perfect adaptation tie uses for which it is designed. (See Bronckns- i Mosher of Boston, Ingals of Chicago and other American experts have also contributed to the elabora- tion of the method. By Jackson's method a strong trie light is carried at the distal end of the tube. Be has also devised many special types of forceps and other appliances, has developed a very succi — fill technique and has written most instructively upon whole subject of bronchoscopy, esophagoscopy, and gastroscopy. Tha art of bronchoscopy is one which seems to require special experience and skill. side ring its extraordinary value in the saving of life, it is only fair to expect that every general hos- pital be prepared to employ it and that at various centers throughout the country there may be found practitioners qualified to extend its aid. D. Brysox Delavan. Johnson: Lancet, October 12, 1S78. Learning: Growths and Foreign Bodies in Air Passages, Diagnosis and Surgical Treatment. Medical Record, 1879, xv., 20S. Wagner: Ziemssen's Cyclopaedia. Holmes' System of Surgery. Mnrell -Mackenzie: Diseases of Throat and Xose, London, 1SS0. Elsberg: Archives of Laryngology, vol. iii., p. 275. Wcist: Transactions American Surgical Association, vol. i., Vbltotini: The Operative Removal of Foreign Bodies and X.-w Growths frrom the Air Passages. Transactions Eighth Inter- national Med. Congres-. Lefferts: Transactions Eighth International Med. Congress. Aiv=Ia=ChapelIe {Aachen), renowned for its hot sulphur springs, is an ancient Prussian town of 100,000 inhabitants, easily reached from Paris, Brussels, or Cologne, being only forty-four miles distant from the latter city. In its ancient and renowned cathedral "are the famous relics of Charles the Great, who has been honored as the discoverer of the springs and founder of the town; but thermal waters at Aachen were certainly known to the Romans," whose pre- dilection for baths and hot springs is well known, as their elaborate remains at Bath, England, and else- where testify. The springs of Aachen were also visited in a.d. 756 by King Pepin the Short. The town is at an elevation of about 565 feet above sea level, is built on sandy soil, and is fairly sheltered by hills. Although the town itself has become entirely modern, its surroundings are very attractive. The climate is moderately moist. The average tempera- ture is 54° F.; the mean temperature for the three summer months is 61.9° F. and for the three winter months 37° F., and the number of rainy days 110. The entire city is underlaid with hot springs, and within a distance of 1,316 meters the water issues from ten springs. The principal ones are the Kai i i quelle (the strongest), with a temperature of 131° F.; tli«> QuirinusquelTe, 122° I'.: the Rosenquelle, 117..".' I.; and the Corneliusquelle, ill I . The waters of the various springs are very similar in mineral con- stituents, differing in temperature and the amount of sulphur thej contain. The Elisenbrunnen, the one most used for drinking purposes, derives its waterfront the Kaiserquelle. At the larger bath establishments, which are elegantly fitted up and arranged, there are vapor baths, inhalation chambers for bronchial and laryn- geal affections, and other rooms set apart for the various hydrotherapeutic processes. "The great advantage of Aix-la-Chapelle," says Baruch, "is the fact that nearly all the baths are situated in five hotels, and there is no necessity, as at Aix-les- Bains, for the patients to be carried in sedan chairs from the springs to the hotels." In the town is a Zander Institute, with medico-mechanical appliances for Swedish gymnastics. Although one can be treated at Aachen at all times, the two seasons are the summer, from April 15 to October 15. and the winter, from November to April. The accommodations are very good, and one can live in the bath establish- ments themselves, as has been said. In 10.000 parts of water, the Kaiserquelle, accord- ing to the analysis of J. von Liebig, contains: Sodium chloride 26. 161 Sodium bromide 0.036 Sodium iodide . 005 Sodium sulphide 0.095 Sodium sulphate 2.S36 Potassium sulphate 1 .527 Sodium carbonate 6.449 Lithium carbonate 0.029 Magnesium carbonate 0.506 Calcium carbonate 1 . 579 Strontium carbonate 0.002 Ferrous carbonate . 095 Silica hydrate 0.661 Organic matter . 769 Total 40.750 Carbonic oxide (free and partially free) 5 000 Traces of fluorine, boron, and arsenic. There is probably an organic sulphide (allyl) present in minute quantity. The action of the Aachen thermal waters, as indeed of all thermal waters, is to increase tissue meta- morphosis and thus to promote absorption of chronic inflammatory products, as in chronic rheumatism and gout; but, as Weber wisely remarks, "hot baths and hot-water drinking are likewise beneficial in these conditions, and it is not certain that the presence of small quantities of sulphur adds much to the effect of hot water"; " the same," he adds, "may be said with regard to some chronic skin diseases." In another place the same writer remarks that in other cases besides those of syphilis the reputation of the Spa is due not so much to the water as to the energetic hydrotherapeutic measures, special exercises, massage, etc., which are employed there. On account of the chloride of sodium which they contain the waters are used in catarrhal conditions of the stomach and alimentary canal and of the bronchi. There are inhalation chambers, as has been stated above, for bronchial and laryngeal affections. The waters are also used in various affections of the abdominal viscera: in sluggish action of the bowels and stagnation in branches of the portal vein, with the resulting dyspeptic troubles; in con- gestion of the pelvic organs and hemorrhoidal vessels; and in enlargement of the liver. Chronic skin diseases, such as eczema and psoriasis, are treated at Aachen with more or less success, "the results obtained, " as one author remarks, "being doubtless partly due to the 173 Aix-la-Chapelle REFERENCE HANDBOOK OF THE MEDICAL SCIENCES medicinal treatment." Besides chronic skin diseases, the following affections constitute the major part of those treated at Aachen: chronic rheumatism, gout, and the stiffness of joints resulting from these affections; metallic poisoning; and syphilis. Cases of the latter disease by far outnumber all the rest, for out of the 20,000 annual visitors at the Spa, 14,000 are said to come there for syphilitic treatment. "The value of these baths in this disease," says Baruch, "has produced such an afflux of syphilitics that the town has obtained quite an unenviable reputation, which prevents, it is said, purely gouty, rheumatic, and other patients from frequenting it." Weber thinks that the reputation of Aix-la-Chapelle in syphilis has been due in great part to the ordinary medicinal treatment employed there and to the attention paid to the subject by the local doctors. Be this as it may, the success of the Aix method of treating syphilis is undoubted. In this country the Hot Springs of Arkansas is perhaps the most renowned place for the treatment of syphilis, and so far as the waters are concerned, it offers essentially the same advantages as Aachen. Sulphur waters similar to those at Aix are found in New York, Virginia, West Virginia, Alabama, Michigan, California, and Ontario, Canada. Edward O. Otis. Aix=Ies=Bains. — This is a town of about 5,000 in- habitants, picturesquely situated in a beautiful valley on the east shore of the Lake of Bourget, and sur- rounded by high mountains (the Savoy Alps). It is about twenty hours from London via Paris and Macon, eight hours from Turin, four from Lyons, and three from Geneva. Its elevation above the sea level is 8.50 feet, and 100 feet above Lake Bourget. The climate is soft and mild, the average temperature being 55° F. during the year, and the mean summer temperature 70° F., though it is sometimes hot in summer. June and September are delightful months. " Owing to its excellent atmosphere," says Linn, "people rest well here." The thermal sulphurous waters, known to the Ro- mans, for which about 35,000 people visit the town annually, are derived from two copious springs which have a temperature of from 107° to 112° F., and which are called " St. Paul's" and the "Alum." They yield about one million gallons of water daily. They are nearly devoid of solid constituents and contain suffi- cient sulphureted hydrogen to give them the charac- teristic odor. " The waters of the two springs are chiefly used for baths, but the 'Alum,' spring is like- wise used for drinking. For internal use, however, t he stronger cold waters of Challes, near Chambery, and of Marlioz are chiefly employed. " The waters and the various methods of treatment employed at Aix are of service in cases in which indif- ferent thermal (or sulphur) waters are of use"; the methods of treatment are probably the most effica- cious in producing the results. "The diseases which receive especial benefit from the Aix treatment are chronic gouty and rheumatic affections, muscular rheumatism, sciatica, neuralgia, neurasthenic condi- tions in arthritic subjects, chronic cutaneous erup- tions, and chronic catarrhal affections of the mucous membranes." "In rheumatic arthritis," says A. B. Garrod, " the value of the Aix course far exceeds, ac- cording to my experience, that of any other known spa." Excellent results are also obtained in the stiff- ness of joints arising from former injuries and from gouty and rheumatic affections. The large bathing establishment is the property of the state, and is one of the most efficient of these in- stitutions known. There are swimming baths (pis- cines), fifty douche rooms with conveniences for ad- ministering massage; six vapor rooms (bouillons); five hot dry-air rooms (etuves) ; two general vapor 174 baths (caisses); and four apparatuses (Berthollet's) for applying vapor locally. There is a special piscina for the treatment of chronic skin affections by prolonged baths, after the method of Loeehe-les- Bains. Poor people are cared for well as the rich. The especial feature at Aix, for which it is so famous, is the " douche massage," consisting of the methodical application, by two skilled attendants, of massage combined with douches. This procedure, which may be used for the whole body or espei i- ally applied to the desired part, is carried out in the following manner: Ihe patient is seated upon a wooden stool, and two attendants, male or female as the case may be, pour the water upon the body from a hose, while at the same time they shampoo, knead, and rub according to the directions given by the physi- cian, who accompanies the patient to the douche the first time, to give instructions as to temperature, force, duration, and pressure on particular parts. The masseurs have each a hose under the arm from which they direct the water over the bather. The "douche massage" may be combined with passive movements of special joints, to be followed or preceded by a vapor bath in the adjoining bouillon. In many cases pa- tients, after walking to the bathing establishment, send back to their hotel their clothes, and, at the close of the bath (which lasts about ten or fifteen minutes), they are rubbed dry, wrapped in a blanket, and carried in bath chairs by porters back to their hotel and put to bed. " The men and women who perform the douche massage have had their art handed down to them for many years, as their fathers and mothers were masseurs and masseuses before them." The Aix waters have an unctuous quality which makes them particularly adapted to rubbing and kneading the musular structures, a quality that is not found in other waters. While using the waters the patient's diet is carefully regulated by the physician. For a more detailed description of the "Aix douche" the reader is referred to that of Dr. Jean Dardel of Aix-les-Bains given in Hinsdale's "Hydrotherap\ ." 1910. Some two thousand douches and one thousand baths are often given daily during the season. The sanitation of Aix is excellent and the accom- modations are ample and satisfactory. The season extends from May to October, though the baths are open the entire year. July and August are the most frequented months. In this country the Hot Springs of Virginia, and the springs of Richfield and Sharon in New York State, correspond to the waters of Aix a~ to the class of diseases treated, and the bathing estab- lishments at these places are modelled after those of the European spas. For much of the above description of Aix-les-Bains the writer is indebted to Weber's "Spas and Mineral Waters of Europe," 1896; to Linn's "Health Res of Europe"; and to the article in the first edition of the Handbook. Edward O. Otis. Ajaccio. — The principal town of the island of Cor- sica, with a population of 20,000. It is situated in the center of a beautiful and well-protected bay open- ing to the southwest. "Fifteen to twenty miles in the rear of Ajaccio is a semicircular mountain chain of granitic formation sloping down to undulating foothills, and presenting a glowing panorama at sun- down. During the winter season the distant peak! of Monte Onto, Rotondo, and d'Oro are capped with snow, and the chilly northeast wind over the gulf of Genoa is dried and broken in force before it reai the western shore, where it is again arrested near Ajaccio by the sheltering hills surrounding the town" (A. Tucker Wise: Transactions of the American Cli- 1 1 iat ological Association, 1890). The visitors' quarter is along the Course Grandival in the northwestern por- tion of the town, "which is the section most protected REFEREXCK HANDBOOK OF THE MEDICAL SCIENCES Alaska and best sheltered from the winds." "The .soil at Ajaccio is disintegrated granite, and allows a rapid disappearance of the heavy .showers which fall during the autumn. But, unlike the Riviera, this locality lias only a small rainfall in March." The water supply is of a pure quality, and is brought I,, I he town from Carazzi, twelve miles distant. " 'I lie drainage of Ajaccio is certainly not perfect," says Wise, "but zymotic diseases are very uncommon." The vegetation is most luxuriant, and all the prin- cipal streets are bordered with avenues of acacia, orange, or citron trees. Bananas, oranges, lemons, a variety of cactus, the castor-oil plant, prickly pear, alec. 6g, and olive flourish. •• 1. at any rate," writes D. W. Freshfield in the Alpine Club Journal, quoted by Ball, "know of no such combination of sea and mountains, ot the sylvan beauty of the North with the rich colors of the South; no region where within so small a space Nature takes so many sublime and exquisite aspects as she does in Corsica. Orange groves, olives, vines, and chestnuts, most picturesque beach forests, the noblest pine Is in Europe, granite peaks, snows, and frozen lakes — all these are brought into the compass of a journey." The accommodations now appear to be ample and satisfactory, both from the standpoint of health and from that of convenience, whether one desires hotel, pension, or villa. As to the meteorology of Ajaccio, the mean tem- perature during the -winter is about 55° F. with a small daily variation of not more than 10° F. ; this is two or three degrees higher than the mean tempera- ture of the Riviera. •' During the season (November to April) the ther- mometer rarely rises above 59°, or falls below 50°" (Hall). The relative humidity is given by Wise as SO per cent., and by another authority as varying be- n 70 and 78 per cent. The average number of rainy days for the season is stated by Wise to be 30, and by the writer on Ajaccio in Eulenburg's " Real- Eneyclopadie," for the months from October to April inclusive, 40 to 45. During the three rainy months, ember, January, and February, the average number is not more than 14, according to Ball. The prevailing wind is the southwest, which is "a tem- perate and soft wind, with genial bright weather, and prevails as a high current throughout the greater part of the winter, and in spring its continuance for a pro- longed period is almost a certainty" (Wise). The southeast wind ("sirocco") is a very depressing one, producing loss of appetite and sleeplessness. "From my own personal point of view" says Wise, "I regard Ajaccio as the most comfortable climate I have ever visited, with the exception of the winters in the Bermudas, and, in comparison with Madeira, it is certainly more bracing and agreeable to the able- bodied." The climate can be characterized as a moderately moist, mild, marine climate, with a com- paratively large number of sunny days, ranking between Madeira and the Italian Riviera, but warmer and more equable than the latter. On account of the hard granite soil there is no dust, and high winds are infrequent, a contrast to the Riviera. " People who find the Riviera too exciting," says Huggard, "com- monly do well at Ajaccio. For young and vigor- ous subjects the climate usually proves relaxing." "It has always been a matter of surprise to me," says Williams '("Aero-Therapeutics," 1S94), "that Ajaccio has not been more utilized as an alternative climate by the Riviera medical men, when their own has proved too stimulating or too marked by radiation extremes, for this mild, moist atmosphere, with its freedom from all but sea breezes, and its good hotels and quiet surroundings, seems to supply the requisite and beneficial change." The phthisical patients for whom this climate is especially well adapted are those who can afford but little physical effort in order to exist — cases of "phthisis of advanced life, with cardiac feeblei where t he powers ot resistance In eold are at a low ebb, or there is much emphysema with cold, livid extremi- ties" (Wise), it is also beneficial for those in whom "the breathing powers an- greatly diminished or when a stubborn cough is a prominent symptom." Those suffering from a dry, irritable, bronchial or laryngeal catarrh are said to do well here. Certain cases of incipient phthisis which are unsuited to the altitude treatment do well in Ajaccio; and the same remark applies to those affected with nervous irrita- bility who require a soothing climate. Ajaccio is reached by .steamer from Nice and from Marseilles in twelve and a half and eighteen hours, respectively. Edwahd O. Otis. Ajowan. — Ajava; Bishop's Weed; IVeed-seed. The fruit of Ptychotis coptica, D. C. ifam. Umbelliferce), This plant is supposed to be indigenous to India, where it has always supplied an important cultivated crop. The fruit — one of the cremocarps commonly called "seeds" — is prized for table use, an equivalent of thyme, as well as for its medicinal properties. It is employed in all cases requiring a carminative, and its action is powerful. It has also been much used in cholera, combined with camphor, on account of its powerful stimulation of the abdominal nerves, and for its antiseptic effect. These uses are fully ex- plained when it is known that the plant contains four per cent, of a volatile oil rich in thymol, and that it is largely used as a source of that substance. Its properties and uses are therefore those of that drug. The dose is one to two grams (gr. xv.-xxx.). H. H. Rusby. Akinesia Algera. — See Acinesia Algcra. Alaska. — This vast northwestern possession of the United States, extending over 16 degrees of latitude and 35 degrees of longitude, and embracing 590,884 square miles of territory, equal to nearly one-sixth of the area of the United States, exhibits a variety of from Greenwich Fig. 66. — Map of Alaska. climatic conditions and contrasts dependent not only upon latitude, but upon the topography of the country and the influence of the surrounding waters and currents. Two great climatic divisions can be made: southern or temperate Alaska, which can be sub- divided into the Sitka, Kodiak, and Aleutian divi- sions, and northern Alaska or the Yukon district, 175 Alaska REFERENCE HANDBOOK OF THE MEDICAL SCIENCES embracing the vast region to the north and west of the Alaskan Mountains. The climate of temperate Alaska is characterized by two striking peculiarities: comparative warmth and great moisture, formerly supposed to be caused by the Kuro Siwo, the " gulf stream " of the Pacific, but "now held to be the general eastward drift of the waters of the North Pacific in the direction of the prevalent winds." As a result of this condition, the tempera- ture is greatly modified from what the latitude alone would lead one to expect, exactly as the climate of Great Britain, for example, is modified by the gulf stream. The isotherm of 40° mean annual tempera- ture, that of the lower St. Lawrence valley, is the mean annual isotherm of the Southern Alaskan coast region. Sitka, with a latitude of 57.03°, which is the same as the latitude of Labrador on the Atlantic coa.-t, has a mean annual temperature of 43.9° F., which is only 2.6° lower than that of Portland, Me., and a mean winter temperature of 32.5°, which is 6.9° higher than that of Portland, and only a little less than that of Washington, D. C. " The coldest month of Sitka, 31.4°, closely agrees with the coldest month of St. Louis." (Greely.) The extreme range of tem- perature is from a point a trifle below zero to 90° above. Similarly, Juneau, in the Sitka district, northeast from Sitka, has a mean annual temperature of 40.9° F. The annexed chart of the maximum, minimum, and mean temperatures of Juneau and Sitka for the year indicate still further the moderate temperature of the region. The second peculiarity of temperate Alaska is moisture in the form of rain or fog, and in the Sitka Average Monthly Maxim™. Minimum, and Mean Temperatures (Degrees Fahrenheit) of Juneau and Sitka for the Four Years 1899-1902 Inclusive. which results in this enormous rainfall, nowhere else equalled in the United States, the annual rainfall at Sitka being more than double that on the Atlantic coast. At Sitka the rainfall for the three winter months is about thirty inches, and for the three summer months sixteen inches. The Sitka region is the scenic portion of Alaska, visited by tourists, and here are found immense glaciers descending into the ocean. The country is heavily wooded with spruce, hem- lock, and cedar, and the vegetation is dense. On account of the sparse sunshine agriculture is difficult, but many garden vegetables are successfully grown. In the Kodiak district, which comprises Cook's Inlet, the peninsula of Alaska, and the Kodiak Islands, the climate is similar to that of the Sitka region, but there is more sunshine and less rain, and the seasonal extremes of temperature are greater. At Kodiak the annual mean temperature is 40.6° F., and the number of days of rain or snow for ten months of the year 1899 was 133, and the number of cloudy days 124, making 2."i7 cloudy and rainy days out of 304. The monthly mean temperature at Kodiak for eight year3 is as follows: Kodiak— Lat. 57° 48'; Long. 152° 19'. Monthly Mean Tem- perature (Degrees Fahrenheit) for Eight Years. August 55.2 September 50.0 October 42.3 November 34.7 December 30.5 Year 40.6 Januarv 30 . February 28 . 2 March 32.6 April 36.3 May 4:i 2 June 49.5 July 54.7 Jan. Feb. .Mar. Apr. May. June. July. Aug. Sept. Oct. Nov. Dec. Juneau — 41 7° 0.5 29.7 .51.0 23.3 35.7 43.0° 12.0 29.1 47.3 16.3 34.3 50.7° 6.0 32 . 8 53.6 7.6 35.8 57 2° 29.5 40.6 58.0 2S.3 42.0 66.2° 33.2 46.6 64.7 31.2 44.6 73 . 2° 39 2 56.6 67.7 34.7 50.6 78.5° 44 57.5 7S.5 40.0 55.5 67.7° 41.7 54.2 65 2 39.7 54 4 63.7° 35.7 49.8 65.0 37.7 50.9 58 7° 27.0 43.0 60.0 30.5 45 2 49.6° 19.3 35.9 54 . 23 3 3S.0 47.6° 11.0 32.6 Sitka— 49.7 21 .3 Daily mean 34.3 division, which extends from Dixon Entrance to William's Sound, the yearly rainfall is from eighty to one hundred and three inches, and there are on an average but sixty-six clear days in the year. " 'When the sun shines, "the atmosphere is remarkably clear, the scenic effects are magnificent, all nature seems to be in holiday attire. But the scene may change very quickly; the sky becomes overcast; the winds increase in force; rain begins to fall; the evergreens sigh ominously, and utter desolation and loneliness prevail." Fogs are exceedingly frequent on this coast and occur whenever the wind blows from the sea. (United States Department of Agriculture, Weather Bureau.) The Sitka district is very mountainous, and the coast bold and steep with few beaches. On account of the fringe of islands lying off this coast and separated by narrow and deep channels called "sounds," there is afforded an almost unbroken protected waterway for ocean steamers from Puget Sound to Cross Sound, one hundred miles or more above Sitka, with many excellent harbors. The mountain sides are densely wooded, and the snow line begins at an elevation of from three thousand to five thousand feet. The prevailing winds being westerly and off the ocean, bring the moisture to the .snowy mountains, which condense it. Hence it is the combination of the mountains, the prevailing moist winds from the sea, and the warm ocean currents, 176 In the Aleutian district, comprising the range of Aleutian Islands, the range of temperature is much the same, as the following chart of Unalaska indicates: Unalaska — Lat. 53° 54'; Long. 166° 24'. Monthly Mean Temperature (Degrees Fahrenheit) for Six Years. January 30.0 August -"'1 9 February 31 .9 September 45.5 March... .30.4 October 37.6 November 33.6 December 30.1 Year 38.7 April 35.6 May 40.9 June 46.3 July 50.6 According to Harriman (Alaskan expedition), there were at Unalaska only eight days in the year, during several years' record, which were entirely clear, the remaining 312 being cloudy and 271 of these were rainy or snowy. The Yukon district, or Northern Alaska, comprises that vast region of the Yukon Valley which extends from the Alaskan Mountains to the Arctic Ocean on the north and Behring Sea and Strait in the west. " If there is a region more infested with fogs than the Pacific coast of Alaska," says Harriman,* "it is Bering Sea." " Here fog is the normal condition, and clear, bright weather the rare exception. It is no uncommon experience for vessels bound for the * Alaska Expedition, vol. ii., 1901. referexce h\ni>ro<>k of the medical sciences Alnjlra I'ribilofs to miss the islands in the fog. and to spend days searching for them, as for needles in a haystack." In the interior of this region the climate becomes colder and drier — extremely rigorous during the long winter and relatively hot in the short summer. As one continues north arctic conditions of climate begin'. On the Behring Sea coast, north of the Aleutian Islands, the winter climate is much more severe than of temperate Alaska on the Pacific coast, hut in summer the difference is less marked. At St. Michaels, on the south side of Norton Sound, the mean summer temperature is 50° F., which is but 4° below that of Sitka: and at Point Barrow, on the \rctic Ocean, the most northerly point in the United : s, the mean summer temperature is 36.8° F. Furthermore, the winter on the Behring Sea coa-t about the mouth of the Yukon River and the Seaward Peninsula is somewhat less protracted and severe than in the interior, although it is still long, and from iber to May the temperature rarely rises above the freezing-point. St. Mr covered there. It is reached either overland— the common passenger route from Skagway by rail for about one 1 hundred mill.- by the White Pass and Yukon Railroad, and thence by steamer on the upper Yukon to Dawson -or by the longer all-water route, which is principally used for freight, by way of the lower Yukon. I he distance from Skagway to Daw- son, the principal city of the Klondike (in Canadian Territory), is five hundred and eighty miles. The general characteristics of the Klondike climate are similar to those of Nome — long, extremely cold winters, with much snow and "brief hut relatively hot summers." "In midwinter the sun rises from 9:30 to 10 a.m., and sets from 2 to 3 cm., the total length of daylight being about four hours." (United States Weather Bureau report.) In June the sun rises about 1:30 in the morning and sets at 10:30 p.m., "giving about twenty hours of daylight, and diffuse twilight the remainder of the time." "During the warmer days of summer the heat feels almost tropical ; the winter cold is, on the other hand, of almost the Jan. Feb. Mar. Apr. May. June. July. Aug. Sept. Oct. Nov. Dec. Year. Mean maximum 33.5° 38.0° 32 0° 40 . 5° 48.5° 62 5° 77.0° 65 0° 56.0° 47.5° 37 0° 34 0° M* tn minimum. . . . —34.0 —20.0 — 17 1) —20.5 —7.0 27.0 40 37.0 25.0 6.5 — i.O —24.0 Mean monthlv. . . —7.4 —2.3 8.9 19.9 33.1 46.3 53.6 51 .9 43.9 30 . 5 15 6 4.8 26.1° Kxtreme maximum 44.0 41.0 43.0 46.0 57.0 7.3 7.5 69.0 69.0 54.0 42 45 75.0 Extreme minimum. -47.0 —41.0 —39.0 —27.0 —2.0 22.0 33.0 32.0 18.0 3 —24.0 —43.0 —47 Mean number of rainv and snowy 7 4 6 S 9 9 12 14 14 11 9 o 108 Extreme cold, however, as one knows from the experience of Arctic explorers, is not detrimental to health, and at Nome, the most populous mining town in Alaska, the winter is said to be the most agreeable season of the year, in spite of the fact that in mid- winter there are but few hours of daylight, the shortest days giving but about three and a half hours of dusky light. " With hands and feet warmly protected, and winter underwear and windproof miter clothes and exercise, one can comfortably weather a degree of cold which, in lower latitudes, would immediately transform him to an icicle. This is due to the dryness of the cold." ("The Land of Xome," by Laurie McKee, New- York, 1902.) The accompanying table, compiled from observa- tions of the U/nited States Weather Bureau, gives the annual and months mean temperatures and the extremes for St. Michaels, which is on the southern of Xorton Sound; it also may be utilized for as- lining approximately the yearly temperature of Cape Xome, which is one hundred and fifty miles listant on the northern shore of X'orton Sound, at its junction with Behring Sea. In the same table will be found a statement of the mean number of rainy and snowy days. As will be seen, the rainfall is light, and is about fourteen inches annuallv. a striking contrast to that of Southern Alaska. One cannot be sure of reaching Xome by sea much before the middle of June on account of the ice in Behring Sea, or of getting away from there after the latter_ part of September or 1st of October. The prevailing winds are from the north, and severe blizzards with strong northeast gales are frequent in winter. In comparing the climate of Xome with "f the Klondike region to be spoken of directly. it may be said that in general the climate of the latter i- rather more favorable than that of the former. The most trying climatic element is the continual wind. The Klondike. — Fifteen hundred miles in the in- r, to the east of Xome City, is the Klondike region, also famed and frequented for the gold dis- Vol. I.— 12 extreme Siberian region." "Yet a beautiful vegeta- tion smiles not only over the valleys, but on the hill- tops, the birds gambol in the thickets, and the tiny mosquito pipes out its daily sustenance to the wrath of man." (Heilprin, "Alaska and the Klondike.") The following observations of mean and extreme temperatures of the United States Weather Bureau made at the Yukon River at the international boundary, about eighty miles north of Dawson, from September, 1889, to June, 1891, will indicate approxi- mately the temperature conditions of the Klondike. From observations made on the Yukon, not far from the site of the gold discoveries, by the l'nited States Coast and Geodetic Survey for a series of six months, the following temperatures are noted: From October, 1889, to April, 1890, the mean tem- perature was as follows: October, 33° (above zero); November, 8° (above zero): December. 11° (below- zero) ; January, 17° (below zero) ; February, 15° (below- zero); March, 6° (above zero); April, 20° (above zero). "The daily mean temperature fell and remained below the freezing point (32° F.) from November 4. 18S9, to April 21, 1890, thus giving 16S days as the length of the closed season. The lowest temperatures registered during the winter were: 32° below zero in X'ovember: 47° below zero in December; 59° below- zero in January: 55° below zero in February: 45° below zero in March; 26° below- zero in April. "The greatest continued cold occurred in February, 1890, when the daily mean for five consecutive days was 47° below zero. The weather moderated slight ly about the 1st of March, but the temperature still remained below the freezing-point. Generally cloudy weather prevailed, there being but three consecutive days, in any month, with clear w-eather, during the whole winter. Snow fell upon one-third of the days in winter, and a less number in the early spring and late fall months. The change of temperature from winter to summer is rapid, owing to the great increase in the length of the day." (Bulletin of the United States Weather Bureau," July 29, 1S97.) 177 Alaska REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Yukon River at International Boundary. Lat. 6o°, Long. 141°. Jan. Feb. Mar. Apr. -May. June. | July. Aug. Sept. Oct. Nov. 39.0° 31.0° 3 0° 66 52. 39.0 14.0 4.0 —35.0 Dec. Year. 2:) 0° 87 (I -60.0 .Mean temperature (degs. Fahr. i Extreme maximum. ■ rue minimum -17.0° —10.0° 25 37.0 -60 . —.35 . 7.0° 3S.0 -45 II 24.0° 56.0 -26.0 45 . 0° 74 8.0 57.0° S4.0 30.0 60.0° 52 0° 87.0 74 35.0 31.0 -16.0° 17.0 19 n Harriman (Alaska expedition) says that the mean temperature of the warmest month on the Yukon, in latitude 64° 41', was 4° higher than at Sitka over five hundred miles farther south; but while at Sitka the extreme range of temperature is 90°, it will be seen from the above table that on the Yukon it is 147°. " With a claim to have seen many distant lands," says Professor Heilprin, "I can truthfully say that never before had it been my fortune to experience such a succession of wonderful summer days as during my stay in t he region about Dawson. From August 6 to September 21), barring three days of partial rain, and perhaps a fourth of cloudiness and mist, the weather was simply perfection — a genial, steady, mild summer, with a temperature rising at its highest to about 80° or 82° F. in the shade." The average annual rainfall is given as from ten to twenty-five inches, and, according to the authority just quoted, the weather is bright and sunny, and there is practically no fog. "There is more sunshine," saj - Harriman, "in a month (in the interior) than at Sitka in a year." Such a climate, although severe, is said to be a healthy and invigorating one to most people, for the cold is uniform and dry, and there is very little wind. a contrast, in this respect, to Nome. In a report by Capt. W. P. Richardson, Eighth Infantry, U. S. A., tin' fact is stated that when the thermometer rises to zero, as it sometimes does in midwinter, it is too warm for comfortable travel. The best temperature, he states, is from 10° to 25° or 30° below zero. " With this temperature the sleds run easily, dogs work with spirit, and one can exercise with the warm clothing necessary at all times in Alaska without discomfort." The ground is frozen deeply, and in the wannest season only thaws to the depth of a foot or two. The vegetation in the Klondike region is, compara- tively speaking, far more luxuriant than at Nome, where it is of arctic character, chiefly mosses and lichens, and the tundra or thick peat moss, or grass which renders foot travelling wearisome and slow. In the Klondike region the country is well wooded, principally with the spruce, although the aspen, birch, balsam, and poplar are found, and this region of forest extends with breaks several hundred miles northward of Dawson. In the summer the country is green and variegated, with a rich flora. Grass grows abun- dantly, and all the hardy vegetables are said to grow without trouble. Grain, vegetables, and fruit have been raised in small quantities. The native strawberry is found in many parts of the Yukon valley, and so also are various native berries, especially the blueberry. In the Yukon valley, near Dawson, celery, lettuce, potatoes, turnips, etc., have been successfully grown, as well as oats and wheat, and this in a latitude which runs through Greenland and Iceland! Of course such results would be impossible were it not for the fait that the summer days, though few, are very hot and the sun is almost continually above the horizon. Fish, furs, and gold are the principal industries of Alaska. The discovery of gold has naturally attracted the most attention, but the fisheries form one of the most important industries, and next in importance to the fur trade is the salmon industry. Large bodies of coal have also been discovered in S mi hern Alaska, but from lack of transportation and the formulation of a definite plan of development by the TJ. S. Government, whose property they are. they have not yet been worked. There are also extensive petroleum fields and copper mines. The population was 64,356 at the census of 1910, about equally divided as between whites and natives. Nome City is the largest town, with a population of over 12,000, and next comes Skagway, with a little over 3,000. Dawson, the principal town of the Klon- dike region, in Canadian Territory, had in 1899 16,000 inhabitants. The testimony is somewhat conflicting regarding the mosquitos, but they are apparently pretty abundant, and at certain times and places constitute a veritable scourge. The gnats are also ven* annoying. The accommodations, especially in the mining towns, are naturally not of the best, and are expensn i still, any one possessed of robust health need mil be deterred either by the climate or by the poor accom- modations from a journey to, or a permanent abode in, Alaska. The steamer accommodations from San Francisco, Seattle, or Vancouver are by some lines quite satisfactory. A summer excursion to the south- eastern coast of Alaska — the iceberg region — is a favorite one, and is in calm waters on account of the protection of the outlying islands. References. — Various government reports from the Interior Department; Department of Commerce and Labor; Department of Agriculture, and the Weather Bureau; yearly reports of the governor of Alaska: Harriman, "Alaska Expedition"; Heilprin's "Alaska and the Klondike"; "The Land of Nome," by Laurie McKee; "The Pacific Coast Pilot," Maj. Gen.Greely's " Handbook of Alaska" and " Alaska Almanac," 1908, and many other special works. Edward O. Otis. Alassio. — A winter health resort on the Italian Riviera, fifty-seven miles from Genoa, and about the same distance from Nice. It is a small town of about 4,200 inhabitants, attractively situated at the head of a curving bay about five miles in width. To the rear is a circle of hills, the greatest elevation of which is on the North (1,963 feet). Thus the town is protected from the winds of the north, west, and southwest, The Mistral (north wind), that bane of the Riviera, is rarely felt here. From the east, however, a strong wind is not infrequent, which, in mid-winter, may !"■ exceedingly uncomfortable. Besides the town proper, there are suburbs at the two promontories at each end of the baj r , in each of which there is a hotel facing the sea. There are hotels and villas on the beach, and on the hill above the town are villas of the English residi and one or more hotels. One can, therefore, obtain comfortable accommodations at a somewhat cheaper rate than at many other Riviera resorts. No accurate information can be obtained as to the sanitary condition of the town, but from its location tin 1 natural drainage ought to be efficient. Sparks ("The Riviera," London, 1879) declared that, the drinking water was good. The scenery is very attractive, with a luxurious vegetation and the picturesque olive groves. "It would be difficult to imagine," said Dean AJford (Ball's "Mediterranean Winter Resorts"), "any place more lovely in spring than Alassio. The somber hoe of the olive is broken by patches of bright green 178 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Albinism here oak and acacia and chestnut lives are bursting !,, leaf. Hoses everywhere with the lavish wealth 1 [taly a cascade of ruses over terrace, walls, balus- ii, ilcs, and trees one glorious mass of bloom. Below, [retching away to the horizon, is the bluest of seas ; hing and gleaming in the sunlight." The following table gives the mean temperatures in degrees Fahrenheit | for the months indicated, uring a period of six years: lotober i;1 '■' January 47.3 April 56.4 ... r .... 54.3 February. ... 48.2 .May 64. 3 !, r . , . 40.7 March 52.3 :iu temperature of the three winter months is, hen, IS. t° 1'. The average rainfall for the above period was ighty inches, and the average number of days per nontfl on which rain fell was 6.6. The mean relative imidity was 57.6, and of the three winter months i 1.7. '' Fog has been recorded on fourteen days [g the six winters." It will be seen from the above that Alassio possesses dry, bracing temperate climate; almost complete of fog, and an abundance of sunshine; and, ition, the characteristics peculiar to a seaside I he cases for which such a climate is suitable are: children suffering from malnutrition and sur- real tuberculosis, particularly glanduar tuberculosis; 2) sufferers from various nervous diseases and ner- ireakdowns, provided they sleep well; (3) cases if heart diseases; (4) cases of gout and chronic rheu- i are said to do well here; (5) convalescents i nte disease; (6) in general, the valetudinarian rom whatever cause, who desires a mild, sunny ilimate where existence is easy, and outdoor life is , issible under attractive surroundings. Patients suf- imin hysteria and melancholia should not be .at here, as the climate is said to aggravate those ■omplaints. I d conclusion, the writer may be allowed to quote a portion of a letter received from an intelligent gentleman who resided at Alassio for some months: The climate in December and January," he says, " is somewhat severe indoors in the Italian houses, but one can be perfectly warm and comfortable in the hotels on the sea beach and in those villas which have been rebuilt or remodelled by the English. But the climate out of doors is delightful even in these two months, when it does not rain, that is, for more than half the time. Early in February acres of riolets for the Paris and even the St. Petersburg market perfume the open air, where they grow quite unprotected, and we had an endless supply of open air roses all through the winter." Edward O. Otis. Albargin. — Gelatose silver,, prepared by evaporat- ing or precipitating a mixture of nitrate of silver and aqueous solution of gelatose. It contains about fifteen per cent, of silver. It occurs in the form of a ciiarse, yellow, light crystalline pow'der, readily soluble in water. It should be kept in the dark. Ubargin is an astringent and antiseptic, employed an intestinal antiseptic, and as a substitute for silver nitrate as an injection in gonorrhea. For the latter purpose solutions of 0.1 to 1 per cent, strength are employed, the stronger solution only in inveterate T. L. S. Albarran, Joaquin. — Born in Sagua la Grande, Cuba, on August 22, 1S60. His preparatory medical studies were carried on partly in Havana and partly in Barcelona, Spain. In 1S77 he removed to Paris and devoted himself to the study of urology under Prof . Guyon in the Necker Hospital; in 1S84 he was ap- pointed an interne in this hospital; in 18S9 he was awarded the faculty prize (a gold medal) for his graduating thesis on " Les reins ih-^ urinaires"; in 1890 he was made Chiei of the Clinic for Diseases of the Uropoietic System and in 1892 he was appointed "Professeur agregeV' From 1901 to 1906 he was Chief of Service in another hospital; and in l'.x iti he was called to succeed Prof. Guyon. It was not long, however, before he began to show signs of breaking down under the heavy strain to which he was subjected. He died in France on January L8, 1912, after a linger- ing illness (t ubereulosis) . Of his contributions to medical literature the follow- ing two deserve special mention: "Anatomic et physiologic pathologique de la retention de l'urine" (in association with Prof. Guyon), 1890; and "Traits des maladies ehirurgicales de la verge." 1896. A. II. B. Albert!, Solomon. — Born in Nuremberg, Germany, in 1540; studied medicine at Wittenberg; and in 1575 was appointed professor of physics. Two years later the chairs of physics and medicine were combined, and Albert! filled the position acceptably for over twenty years. Having been chosen by the Elector of Saxony as his chief physician, he transferred his residence to Dresden, and died in that city on March 29, 1600. His chief distinction rests upon the fact that he was honorably esteemed as an anatomist. According to Haller he was the first to publish an actual picture of the valve of the colon; he had drawings made of some venous valves; and he also furnished more complete descriptions of the anatomy of the tear duets. Portal is authority for the state- ment that Alberti described very accurately the little bones of the cranium, the discovery of which some authors," insufficiently informed," have attributed to Olaus Worm. Alberti also published interesting researches in relation to the brain, the sinuses of the dura mater, etc.; and he described the anatomy of the ear in great detail. A. H. B. Albinism. — Synonyms: Albinismus, congenital achroma, leucasmus, leucoderma, leueopathia, leucism, leucosis, leucynosis, kakerlakism. The term albinism (Latin, albus, white), or con- genital leueopathia (Greek, Xewcos, white, and TzdOos, affection), is used to designate the peculiar condition characterized by congenital absence of pigment in the skin, hair, choroid, and iris, and which is classed under the atrophies. Although albinism has been noted from the earliest historical period, the Portuguese are the first on record to have named this lusus naturce, which they met now and then among the negroes on the western coast of Africa. These abnormal indi- viduals they called albinoes. In some of the African courts, especially in Congo, they are venerated and are known as " dondos." The term "leuca?thiopes", i.e. white negroes, has been applied to them. Extensive investigations have been made in regard to the origin of pigment in the skin. Various workers have reached the conclusion "that the pigment in the epithelial cells is carried there by special connective tissue cells (chromatophores) which wander up to or actually in between the epithelial cells to supply the pigment." However, still later work gives strong evidence " that pigment can be produced without the transfer by aid of chromatophores." Concerning the etiology of albinism there have been numerous theories many of which have been thor- oughly unscientific. Some investigators have attempted to attribute to albinism a pathological origin. Indeed, in early times, albinoes were considered a sort of leper, and consequently were avoided and shunned in life, while after death the bodies were throw-n on a dunghill unburied. On account of their faulty vision by day, and their custom of appearing most 179 Albinism REFERENCE HANDBOOK OF THE MEDICAL SCIENCES frequently at twilight, since their sight is most per- fect at this time, they were contemptuously called " cockroaches." Consanguinity in marriage has been considered an etiological factor, an example being noted by Darwin, in which " two brothers married two sisters, their first cousins, none of the four nor any relation being an albino; but the seven children produced from this double marriage were all perfect albinoes." A theory has been advanced connecting inactivity of the suprarenal bodies with deficiency in pigment and so with albinism. Also excessive function of the carbon-eliminating organs has been suggested as a causative factor, as well as constitutional insufficiency of iron. Albinism has been ascribed to certain disturbances of the nervous system. The affection has been said to be endemic in some tropical countries. Maternal impression has also been suggested as the cause. Another theory considers that the formation of pigment may be due to the action of a ferment. Con- sequently albinism would result from the absence of this ferment. The theory of arrested development must be true in a certain sense but nevertheless it does not account for anything. " If the distinction between the nor- mal and the albinotic be assumed to be an absence of pigment, and if pigmentation normally begins to appear during fetal life, then albinism is distinctly an arrest of development." This theory merely asserts " that albinism is a pre-natal defect, not excess, of development. It is quite consistent with any modern theory which asserts that albinism is due to the absence of one or more development controlling determinants in either one or both parents. It is little more than the statement of an obvious fact, as far as concerns pigmentation." Heredity, as the chief etiological factor in albinism, has been as vigorously upheld as it has been sharply attacked. There are instances on record of families of albinoes. These are very rare, however, and have been said to be observed only in the tropics. It is well known that the offspring of an albino and a black is generally the pure type — either universal albino or black; though some cases of partial albinoes have been reported. However, the children of a normally pigmented individual and an albino are usually not lacking in pigment. Also healthy, normal parents have had albino offspring. In several instances families have been observed in which universally pigmented children have alternated in birth with albinoes. A very recent hy-pothcsis advanced is " that albin- ism is an hereditary defect of structure, and possibly only of superficial tissue structure, which interferes with the normal metabolic process by which pigment is produced and stored. The absence of pigment is a secondary result of the albinotic structure, and not the primary source of the albinotic constitution. The delicacy and thinness of the albinotic tissues, their resulting increased vulnerability, and diminished resistance to thermal, luminous, and mechanical in- fluences are not solely due to the absence of pigment; it is suggested that they mark a differentiated tissue structure on which the absence of pigment itself depends. There are many ways by which this hypothesis can be tested, and such tests will be fruitful even if the hypothesis has to be dis- carded." (Draper's Company Research Memoirs, Biometric Series vi.) Casting aside first the theory that albinism is a disease ami secondly the theory of arrest of develop- ment, and accepting as the only or at least the chief source of albinism "the inheritance of an abnormal tissue 1 structure," we are then in a position to put albinism in the category of "other forms of inheri- tance of abnormal structure." In addition, we shall be able to put the hypothesis to proof " by ascertaining whether its inheritance follows the same laws' All facts being considered, we may conclude that " the essential pathological characteristic of albinism" j~ not the mere absence of pigment but the condition of the tissues lacking pigment — in other words, tin- texture of these structures. As to the sex in which albinism most frequently occurs, both male and female seem to be equally repre- sented, different authors inclining toward one or the other according to their individual observations. Albinoes have been known in all climates and among all races. Albinism is more common in colored than in white races. Albinism may be universal or partial. In univer- sal albinism the appearance of the individual is very striking. The skin is absolutely lacking in pigment, though there is sometimes a slight reddish tinge from the circulating blood underneath the translucent sur- face, the characteristic complexion having a dull waxen pallor. The skin is often roughened, scaly, or scurfy, a condition which is easily- explained by it. extreme delicacy of structure and the consequent effects of its exposure. It is often covered with a soft white down, though sometimes it is perfectly smooth. The whole hairy system is colorless. This may he due to the absence of iron in its composition, as in the chemical analyses of hair of various colors, made by the French chemist Vauquelin, black hair has been proved to contain iron, while white hair lacks this element. The texture is peculiarly fine, glossy, and silky. Although the hair is colorless, its appearance is not that of hair whitened by age, but rather that of flax or corn silk. There is one case on record of an albino having red hair (Folker). In the albinoes of the black race, the hair, though white, is as woolly and the features as characteristic as those of their black brothers. Although the appearance of the eye in this condi- tion differs so widely from the normal, "the patho- logical significance of albinism lies solely in the fart that the iris or diaphragm of the ocular camera is transparent, or so nearly so that it does not act as a true photographic or physiological diaphragm'' (Gould). This deficiency^ of ocular pigment brings in its train much pain and discomfort. The usual color- ing matter of the eye being absent, the pupil looks bright red from the rich background of blood-vessel-, and the iris light pink or a very delicate blue, tin variations in tint depending upon the angle of observa- tion and the nature of the illumination. Photople is present in the highest degree, the characteristic position of the albino in daylight showing him with one arm held up as a shield for the eyes. There is perpetual nictitation — rapid and repeated motion of the transparent eyelids, which open and shut con- tinually in the double effort to see, and at the same time to exclude the overpowering amount of light which has free access to the inner parts of the eye The iris is constantly expanding and contracting. Nystagmus, or oscillation of the eyeballs, which is present, is due to the effort to obtain a clearer vv« of the objects of vision. Amblyopia is a serious fea- ture in albinism, various causes cooperating to pro- duce it — viz., ametropia, which increases with the age of the albino, and which is due to pressure on the i ball in the effort to exclude light, retinal exhaust i and nystagmus. Myopia is also common. It has been generally supposed that albinoes are weak both in bocty and. in mind, but this is by no means always true. Often the albino member of :i family has been intellectually the strongest, many el these unfortunates being particularly shrewd. Partial albinism, more common in negroes than in white people, is observed as one or more patches, colorless or pinkish, generally circumscribed and ir- I.SII REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Albuminuria regular, of any size or form. Instances have been noted, however, in which these patches were sym- trically disposed, corresponding to the course of peripheral nerves, as similarly happens in the case of certain pigmentary and verrucose nsevL They may be in any pari of the body, being most c< non, how- ever on the scalp, face, dorsal surface of the hands, pies, and genital region. The hair on these spots , nerally while. The eyes are usually normal, bowing the ordinary amount of pigment, though I may be bluish or pinkish. Negroes having this affection are called pied or piebald. The hair is flaxen ,,l. These patches generally remain permanent iugh life, or they may gradually extend (ill they include a large surface; they have been known to change to a normal appearance through a redepdsi- tion of pigment, although this is rare. Work by the most recent investigators calls atten- iii "the relative rareness of complete albinism, ie spotted or splashed condition, and of xanthisin, and their relatively frequent coincidence in the same L." Such conditions would seem to point to the that these abnormalities of pigment conditions arc not entirely independent. It may be accepted reasonable working hypothesis that these various conditions complete, partial, and incomplete albin- and xanthism, "all static forms of leucosis, are phases of tin' same process and are probably linked « ith leucoderma and possibly other forms of dynamic losis In albinism as in many other defects, we find equivalence or interchangeability of dity." These workers look forward to still further -ligation of this subject from the various stand- >f pathology, physiology, and genetics. Albinism has been noted not only in man, but also in the lower animals, and among plants, a very com- mon example among animals being the pink-eyed white rabbit. It is seen in elephants, otters, horses, cows, hogs, dogs, cats, squirrels, rats, mice, raccoons, ferrets, hooting owls, leather-wing bats, doves, chick- ens, pigeons, parrots, blackbirds, robins, martins, swallows, sparrows, and the silver variety of gold- fish. Some animals become white physiologically in winter. This is not an example of true albinism. It lias been suggested that the etiolation of plants kept in the dark may belong in the same category, but this differs from persistent lack of pigment, since color returns on exposure to light. As to the therapeutics of albinism — there is abso- lutely no remedy for the affection. Emma E. Walker. Albinus, Bernard Siegfried. — Born at Frankfort-on -the-Oder, Germany, February 24, 1697. The fam- ily name was Weiss, but at some period of the six- teenth century it was latinized into Albinus. The father of Bernard Siegfried and his two brothers (Christian Bernard and Jakob) were all of them physicians of considerable distinction. Bernard Siegfried studied medicine at the University of Leyden, Holland. From the very beginning he showed a strong predilection for anatomy and botany, branches of medical science which were then being taught at Leyden by Boerhaave and Rail. In October, 1719, he was chosen Instructor in Anatomy by the Faculty, the degree of Doctor of Medicine having been given to him only a short time previously. Two years later he was made Professor of Anatomy and Surgery in the same university. In 1726 he published his treatise on osteology, and he was engaged, at about the same period, in assisting Boerhaave in the prep- aration of an edition of the works of Vesalius. In 1734 he published his History of the Muscles of the Human Body, a work which was remarkable in at least two respects: it was most beautifully illustrated, and the individual figures were drawn with great delicacy and with almost perfect correctness. In L736 and 1 7: ;7 he published two other works of importance — a treatise on the veins and arteries of the intestines, and one on the seal of the color of the skin in negroes and other dark-skinned raci and on the causes of this coloration. In 17".s lii- was chosen Boerhaave's successor as President of the College of Surg is al Leyden, and he was also (for the second time) made Rector of i he University. In addition to all his other work Albinus, during this very busy period of his life, never lost sight o£ the two undertakings which he considered of the greatest importance — viz., the preparation and publication of a commentary on the anatomical plates of Eustachius, and the construction of his ow n large plates. As the health of Albums was beginning to be affected injuriously by his spending such a large proportion of his time in the atmosphere of the dis- secting-room, the curators of the university made him Professor of Medicine in 174"). His younger brother was appointed his successor in the Chair of Anatomy. Bernard Siegfried Albinus died Septem- ber 9, 1770. Of his fairly numerous contributions to medical literature the following deserve to receive special mention:" De ossibus corporis humani ad auditores suos libellus," Leyden, 1726 (reprinted in 1762); " Historia musculorum corporis humani," Leyden, 1734 (Frankfort, 1784); "Dissertatio de arteriis et venis intestinorum hominis," Leyden, 1736 and 173S; "Dissertatio secunda de sede et causa coloris jEthi- opum et ca?terorum hominum," Leyden, 1737; " Icones ossium foetus humani: aecedit osteogenic brevis historia," Leyden, 1737; " Explicatio tabularum anatomicarum Barthol. Eustachii," Leyden, 1744 and 1761; "Tabuke sceleti et musculorum corporis humani," Leyden, 1747; "Tabulae ossium humah- orum," Leyden, 1753; and " Academicarum annota- tionum libri VIII," Leyden, 1754-1768. A. H. B. Albucasis (Abul-Casem-Khalaf-Ebn-Abbas.) — The last one of the Arabian physicians whose writings have been preserved up to the present time in the form of Latin translations. He was born in Zahara, near Cordova, Spain, reached the period of his greatest celebrity at the beginning of the twelfth century, and died in 1122. According to the opinion of Schenck, stated in his " Biblia iatrica," Albucasis and Alsa- haravius were one and the same person. The great treatise on the theory and practice of medicine (en- titled "al Tasrif"), which is commonly accredited to Alsaharavius, is therefore the work of Albucasis. While parts of the book have gone through numerous editions (1471-1602), the work as a whole has been printed only three times. Albucasis was the first to describe the affection popularly termed "milk*tetter" (crusta lactea), the symptom known as dysphagia, and mercurial salivation; and he was also familiar with tetanus, smallpox, the aphthous affections of childhood, and a variety of mental disorders. " But his three books on surgery constitute one of the most precious monuments of the twelfth century." (Dic- tionnaire historique de la medecine, etc.) A.H.B. Albuminuria. — Albumin is a normal constituent of human urine in the same sense as is glucose, that is, neither can be demonstrated in the renal secretion by ordinary clinical tests but both are found in traces when the urine is subjected to refined methods of examination. This normal albuminuria, clinically of no interest whatsoever, is not analogous to that which Senator, for instance, understands by "physi- ological albuminuria" when he declares that_ the increase of urinary albumin ensuing after consider- able bodily exercise, a diet rich in proteins, cold baths, and during menstruation is a physiological 181 Albuminuria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES phenomenon. Senator evidently does not consider the facts that physiological circumstances may give rise to pathological effects, and that the frequency of a pathological occurrence is not a criterion by which its physiological character can be determined. En- demic goiter for instance, so frequent in certain moun- tainous districts and of probably pure physiological causation, is nevertheless a disease, and it occurs to nobody to describe it as a physiological manifestation. The conception of Senator is shared by other authors who assign to physiological albuminuria a wider scope than can be conceded by him who rea- sons by analogy. If, for instance, the output of glucose by the urine be ever so small in a clinical sense, the trained observer will never designate it as a physiological occurrence. He may accept a normal glycosuria in the same sense as I admit the possibility of a normal albuminuria, for glucose will invariably be detected in large amounts of artifi- cially concentrated urine, but he will never speak of a physiological glycosuria if he discovers sugar in the native urine by his every-day reagents. Withal, no evidence has as yet been brought forth that the protein substance, excreted in tangible amounts after bodily or psychical exertion, is iden- tical with the protein which is present in every urine. The true character of the latter is not only unknown, but there is also sufficient proof that we do not always have to deal with the same albumin body, and that there may occur diverse kinds of protein, succes- sively or together, in the manifold forms of so-called physiological albuminuria. Normal albuminuria is a fact, but it is and re- mains an academic issue as far as the practitioner is concerned. Whenever albumin can be demon- strated in the native urine by the ordinary clinical methods, we are confronted with an abnormal con- dition. Normal albuminuria is the only feasible physiological albuminuria, and every albuminuria recognized by routine examination, and be it ever so slight or evanescent, is an abnormal albuminuria. Clinical Albuminuria. — Clinical albuminuria is always a tangible fact. It is due to the appearance in the urine of one or more proteins, in the vast ma- jority of instances of dissolved serum albumin together with serum globulin (paraglobulin). The native serum proteins do not always occur in the urine in the relative amounts in which they exist in the blood serum wherein they are found on the average in the proportion of two parts of globulin to three parts of albumin. As a rule the serum albumin preponder- ates in the general run of chronic cases of albumi- nuria, but a genuine serinuria (the excretion of serum albumin alone) is an exceedingly rare occurrence. In maivy instances of acute nephritides, on the other hand, globulin seems to be the prevailing urinary protein. As a matter of course, we treat now and in the following pages of genuine albuminuria only, and not of the spurious variety which is the result of the admixture of adventitious protein substances like pus, lymph, blood, prostatic secretion, etc., with a urine that was free from protein material when it had just traversed the renal parenchyma. While clinical albuminuria in itself is an abnormal incident, it is no! of necessity the result of a demon- strable pathological state. True enough, at its foun- dation, especially if it be of a chronic nature, stands very frequently a permanent structural lesion, but then it is invariably associated with a chain of more or less pronounced pathological features which have a definite significance in the majority of the cases. However, when the albuminuria is the most prominent or even the only abnormal phenomenon, the true state of affairs underlying it, for the reason that it is often of a functional and not an anatomical charac- ter, is disclosed in a comparatively small number of instances only. Albuminuria without ascertain- able cause may be transitory, as is frequently the 182 case; it may, however, tend to recurrence or may be persistent. Albuminurics of this class may enjoy the best of health, and their metabolic equilibrium is often perfectly maintained for long periods They may attain a good old age, and they generally die from other than renal diseases. The albuminuria, and may it be ever so evanescent, is nevertheless an abnormal occurrence, and even if its cause be not determinable by the clinical means at our disposal a cause there must be. Medical writers generally differentiate between "functional" and "pathological" albuminurias. How- ever, the clinical albuminurias are of necessity abnor- mal circumstances, for were it not so, why does not every urine exhibit ascertainable amounts of albu- min? All "functional albuminurias," the scope of which has heretofore been too narrowly drawn, are albuminurias of pathological function; they are just as pathological as the "pathological albuminurias" of former writers. The only difference between tin albumin output of these two arbitrary forms of albu- minuria is possibly that of degree; this, however, is not invariably the fact. The greater part of this encyclopedic statement is devoted to a discourse of the group of albumi- nurias at the foundation of which there apparently stands one or the other perverted physiological function. Albuminuria symptomatic of structural disease, sufficiently understood by the practitioner even if only on account of the accompanying clinical features, is dealt with in a casual manner only. Renal affections, as such, are not dwelt upon at ail, neither are the other diseases during the course or in the wake of which albuminuria may supervene. Albuminuria Due to Patholoqical Function. — By albuminuria due to pathological function is under- stood the occurrence in the urine of clinically deter- minable amounts of serum albumin and serum glob- ulin in the absence of any demonstrable anatomical disease of the kidneys. This group includes, however, albuminurias which are the result of malposition of, and undue traction or pressure upon an otherwise normal kidney. In the latter instance the albumin- ous urine is not infrequently excreted by one kidney only. Besides the albumin, the urine of this group of albuminurias generally exhibits no abnormal features. The diurnal amount of the excreted albumin varies greatly and may be considerable, but does not exceed one or two grams in the majority of cases. In the presence of a definite renal lesion, on the other hand, the twenty-four hours' urinary albumin output usually amounts to from five to ten grains and may exceptionally attain a much higher figure. A transient albuminuria may obtain in a healthy individual without any recognizable cause. E such cases must be considered as the result of a patlio- logical function inasmuch as there is no physiological albuminuria which is clinically demonstrable. No matter how insignificant and fleeting the exciting cause it must have been of sufficient impetus to give rise to a disturbance of function somewhere in the organism. A long-continued functional disturbanci may develop into a state of pathological physiology in which the abnormal phenomenon — in this instance the albuminuria — bears less a frankly pathological than a compensatory character. Many functional albumi- nurias are compensatory manifestations of some non- renal deficiency or disturbance. The "compensatory albuminurias," as the writer 1 has termed them, although not pointing to a kidney affection are, no theless, of a decidedly clinical nature. Compensatory Albuminuria. — The various transi- tory types of albuminuria have been considered by some to reflect a specific or latent form of nephritis while others have viewed it as an expression of a tem- porary disturbance of renal function. Langstein's autopsy findings have finally done away with the first assumption, at least so far as the orthotic type of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Albuminuria dbuminuria is concerned; the latter supposition nerely substitutes a derangement of renal activity or aii anatomical renal lesion — a conjecture which loes not bring us one step nearer the solution of ted question. \n albuminuria cannot ensue if the cells of the cidney are impermeable for the large albumin molecule. We know, however, that the structurally sound renal nembranes permit under certain circumstances the lassage of albumin from the blood current into the Is this transudation of the large albumin mole- through the normal kidney membranes referable to oerted function or to a compensatory response of the i.e. is the o Hi ii miliaria due to deficiency or efficiency , rial action; to a renal, exclusively local, functional \\ eoiii/n li neij or to anterenal pathological influences .' The kidneys regulate the composition of the blood. When their work is not interfered with the amount of - arii his urinary constituents ordinarily reflects the omparative quantity in which the same substances have existed in the blood. However, when the renal activity is lowered, be it on account of functional or rphological circumstances, there will be retention ol the urine-making substances in the blood and a lortional deficiency of them in the renal secretion. lertony of the blood plasma in the presence of idly functionating kidneys can be only a transi- tory occurrence, and if there be a hypotony of the ma tin' regulatory function of the kidneys will ion correct it. Thus, the kidneys tend to maintain a rather definite concentration and osmotic tension of the blood for every period of life. Substances which contained in excess or are foreign to the blood invariably reach the kidneys whence they are elimi- ited. (While water and the normal catabolic prod- ucts do not alter the constitution of the sensitive renal membranes, blood-foreign material is liable to t the function of the renal cells and may cause their structural damage if large amounts of it are continuously brought in contact with them through the medium of the circulation). This fact again demonstrates the blood-regulative ability of the kidneys, and also evinces that the appearance in the urine of certain so-called pathological substances is not of necessity due to diseased excretory organs, but that it may be, on the contrary, a manifestation of their healthy and vigorous condition. The occurrence of albumin in the urine in the pres- of structurally sound and functionally efficient kidneys must be designated as a regulatory act of the litter. By their regulatory capability the renal organs tend to compensate for the insufficiency of those organs which have permitted entrance into the circulation of blood-foreign albumin, or to the incom- petency of which is due a peculiar physicochemical blood composition, demonstrating itself in the defi- cient power i'f attaching the absorbed protein material. In a limited sense, that is as far as the interchange between blood and urine is concerned, we may speak nf regulatory albuminuria; in so far, however, as the blood-foreign protein or the abnormal blood compo- sition is the outcome of perverse metabolic processes, we are justified in describing the resulting albumi- nuria as compensatory in character. While, as a ter of course, a non-nephritic albuminuria cannot ensue without renal regulatory activity, the causative factors of compensatory albuminuria are anterenal in time as well as location, and are entirely independ- ent of the kidneys. The designation "compensatory inintiria" is therefore much more comprehensive mid expressive than either the terms "regulatory albuminuria," chosen by Rosenbach, or "hematogenic albuminuria," propounded by Bamberger. Although regulatory albuminuria corresponds in many respects with compensatory albuminuria, its most distinctive factor is deemed to be the regulatory function of the kidneys, while the conception of compensatory albumi- nuria sees in the regulatory activity of the kidneys not a selective-voluntary, but, more properly, a com- pulsatory operation. On the other hand, the rather indefinite so-called hematogenic albuminuria (l food products rich in albumoses. Artificial preparations g :i^ albumin substitutes often exhibit a large proportion of albumoses. Such artificial products are frequently prescribed in gastrointestinal affections and during convalescence from acute forth ing, the blow received by the unsuspecting former proposer lor life insurance is in realitj a great boon to him, for now he knows I hat a change in his mode of life, con fnrin ing to I he decreased demands and functional activity of bis organism, i^ imperative. Febrile Albuminuria. In many of the acute diseases there may ensue an albuminuria which endures with or without intermissions during the febrile stage. An albuminuria developing in l he course or in t he wake of a febrile disease may, of course, be a manifestation of a nephritic process; in the preponderating majority of instances, however, there exists no .structural disease of the kidney. The albuminuria usually vanishes with the decline of the fever, and appears never to be associated with any permanent disturb- ance of the renal function. The amount of excreted protein varies and depends entirely upon the intensity of the toxic process. In rare instances the protein output may be so abundant that it may be impossible to differentiate between this type of albuminuria and an actual nephritis. The temperature elevation as such does not influence the protein output. The albuminuria may be due to several factors working synchronously or successively. At the onset of the affection it may be deficient renal blood supply (ischemia) and at a later stage, especially in grave cases, renal hyperemia to which the advent of the albuminuria can be attributed. In either eventuality the albuminuria may be a compensatory phenomenon. The albuminuria in typhoid fever complicated by meningism is probably not alone dependent upon the bacterial toxin circulating in the blood but also, in some degree at least, to an irritation of a portion of the central nervous system. In influenza there may ensue an active renal hyperemia characterized by an insignificant serumalbuminuria and globulinuria. The moment the influenza poison is eliminated or neutralized, the albuminuria ceases and the renal incident of influenza closes there and then. 19 In other infectious diseases, particularly in scarlet fever and diphtheria, the bacterial poisons may directly and permanently injure the renal parenchyma. It is also possible that the excreted protein in some of the minor febrile albuminurias is neither serum albumin nor globulin but toxalbumin due to bacterial activity. This, at least, is Krehl's suggestion who n mmends differential testing for the urinary proteins.. The albuminurias of this class are erroneously termed febrile as it is not the thermic but bacterio- toxic influences to which their origin must be assigned. A more appropriate designation would therefore be " bacteriotoxic albuminuria." Toxic Albuminuria. — Besides febrile albuminuria which is in some respects a toxic albuminuria there occur albuminurias as the consequence of poisoning with certain chemical substances. While there can be no doubt that the ingestion of agents like oil of turpentine, cantharides, mustard, and mineral acids, when undiluted or insufficiently diluted, is liable to be followed by renal irritation or even structural disease, it is also true that the specific toxic albumin- uria may arise in the absence of a kidney lesion. This is particularly the case when an albuminuria ensues after the introduction of chemicals like arsenic, phosphorus, phenol, mercury, iodine, salicylic acid, and potassium chlorate and nitrate. Such toxic albuminurias are due to disturbances in the general and renal circulation and to an altered blood com- position. Here again the protein excretion is refer- able to an effort on the part of the kidneys to com- pensate for anterenal difficulties. The heretofore sound kidneys remain sound if the toxic process called forth by these agents declines within a short time. Even the presence in the urine of hyaline casts and some fresh blood after the introduction of such chemicals does not indicate nephritis. In the average case soon after the toxicosis has ceased, 1S7 Albuminuria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES there is no longer any albuminuria, nor can casts or blood be demonstrated. Hematogenous Albuminuria. — There is no con- sensus of opinion as regards the nature of hematog- enous albuminuria. This type of albuminuria accompanies affections like pernicious anemia, leu- cemia, scurvy, diabetes, etc. Many clinicians believe that the renal structures participating in urine pro- duction have become deteriorated and pathologic- ally altered in the course of these systemic diseases, so as to be rendered permeable for the albumin mole- cule. Though there can be little doubt that the kidneys may in time become involved in the general process of bodily decline, there is no evidence that there commonly exists renal deterioration in the early stages of these affections. The characteristic hema- togenous albuminuria which prevails before neph- ritic changes have taken place is virtually a toxic albuminuria and is almost entirely due to qualitative and quantitative changes in the circulating protein. The abnormal excretory work of the kidneys in these in- stances must be regarded in the light of a regula- tory or compensatory process. (See Compensatory Albuminuria.) Postepileptic Albuminuria. — By the term postepi- leptic albuminuria is understood the occurrence of urinary protein after an epileptic attack. While some observers have found the protein in the wake of every seizure, others assert that it appears only occasionally, and a few others have failed altogether to detect it after the attacks. The truth of the mat- ter seems to be that the urinary protein appears quite irregularly; in the same individual even it may occur after one seizure and may be absent after another. Postepileptic albuminuria may be due to a latent nephritis temporarily activated by an epileptic paroxysm; to circulatory renal disturbances concurring with the seizure and manifesting them- selves mostly as passive congestion; or to toxins in the circulation prior to and during the attack. The first eventuality assumes an out and out nephritic hcaracter of postepileptic albuminuria which, however, is displayed in only a certain proportion of the cases. We possess sufficient proof that eventual chronic kidney changes may be of an entirely secondary nature, and that the majority of instances of post- epileptic albuminuria arise on a non-nephritic basis. There is little doubt that circulating toxins, and especially disturbances in the blood supply of the kidneys stand at the foundation of this type of albuminuria. The one eventuality would stamp it a toxic, the other a recidivating albuminuria. Mun- son 20 who has examined .'543 epileptics, 197 men and 146 women, for the albuminuria following epileptic seizures, summarizes his observations, thus: (1) postepileptic albuminuria is found in about twenty per cent, of epileptics; men are much more frequently affected than women, and severe seizures are more likely to cause the condition than are mild attacks; (2) the condition is not constant in the same individ- ual; (3) the presence of albumin is almost invariably associated with the finding of casts, sometimes in great numbers and variety; they persist longer than the albumin, but may also be found in the inter- paroxysmal period in the absence of albumin; (4) the first appearance of albumin may be at any time within the first two hours after the attack and it may not disappear till the fourth day; (5) physical examinations are not fruitful of diagnostic results, except that a few slight heart findings are noted; the blood pressure is elevated in some of the cases; (6) in a series of cases of death in or shortly after seizures, congestion of the kidneys is almost constantly found, with albumin in the lumen of the tubules; there is also a good deal of chronic change which, it may be assumed, is due to the congestion, so often repeated. Postepileptic albuminuria is not the only so-called neurotic albuminuria, for a transient excretion of urinary protein has been observed in hyperthy- roidism, apoplexy, progressive paralysis, brain tumor delirium tremens, etc. The cause of neurotic albu- minuria has been ascribed to the stimulation of the albuminuriogenic center of Bernard situated in the floor of the fourth ventricle; however, it appears fco be due to exactly the same factors which may occa- sion the postepileptic albuminuria, i.e. circulatory disturbances in the kidneys or a toxic state of the blood. Thus the albuminuria of Graves' disease is undoubtedly of hyperthyrotoxic origin. Heinrich Stern. 1. Heinrich Stern: Compensatory Albuminuria, a Contribu- tion to the Study of the Clinical Albuminurias, -Medical 1;, June 26, 1909. 2. Langstein: Die AJbuminurien alterer Kinder, Leipzig. 1907. 3. Virchow: Verhandlungen d. Gesellsch. f . Geburtsnilfe, 1846. 4. Pavy: The Lancet, 18S5. 5. Edel: Munchener med. Wochenschr., Nov. 19, 1901. 6. Edel: Deutsche med. Wochenschr., Sept. 3, 1903. 7. Jacobsohn: Berliner klin. Wochenschr., Oct.. 5, 1903. 8. Sutherland: Am. Jour. Med. Sciences, Aug., 1903. 9. Beck: Am. Jour. Med. Sciences, Sept., 1903. 10. Jehle: Munchener med. Wochenschr., Jan. 7, 1908. 11. Nothmann: Archiv f. Kinderheilkunde, Vol. XLIX, Nos. 3 and 4. 12. Hamburger: Wiener klin. Wochenschr., 1912, No. 25. 13. Lury: Jahrbuch f. Kinderheilkunde, 1910, p. 705. It. Uhlenhuth: Deutsche med. Wochenschr., 1900, p. 734. 15. Inouye: Deutsches Archiv f. klin. Med., March, 1903. 16. Oroftan: Archives of Diagnosis, Oct., 1908. 17. Ascoli: Zeitschr. f. physiolog. Chemie, 1903, p. 2S3. IS. Wells: Jour. A. M. A., Sept. 11, 1909. 19. Heinrich Stern: Renal Complications and Sequela? of Influ- enza. Medical Record, Jan. 11, 1908. 20. Munson: N. Y. Med. Jour., Nov. 27, 1909. Alburgh Springs. — Grand Isle County, Vermont. Post-office. — Alburgh Springs. Access. — The Canada Atlantic Railroad runs through the village. The Central Vermont Railroad is within a mile of the village; thence one mile to Springs hotels. This is an old-time New England resort, which has been in use since the year 1816. The springs are located on the shores of Missisquoi Bay, and are sur- rounded by picturesque lake and mountain scenery. The situation is thirty feet above the level of Lake Champlain and about eighty rods from the water's edge. There are two springs, one of which was analyzed by Dr. C. T. Jackson, in 1868, with the following results: One United States Gallon Contains: Solids. Grains. Sodium sulphate 7 11 Potassium sulphate with potassium sulphide 9.50 Sodium chloride 8 T ' . Magnesium chloride 5.02 Calcium chloride with calcium sulphate 4.81 Insoluble matter Ml Organic matter, acid, and loss 2.00 Total 38.00 The water gives off a large quantity of sulphureted 1 hydrogen, and may be placed in the saline sulphureted class of mineral waters. We are informed that an analysis by Professor Chandler, of New York, shows also the bicarbonates of lithium and strontium. The other spring in the neighborhood is of a ferruginous character. Emma E. Walker. Alcaptonuria. — A rare condition, first described by Bodeker in 1857, in which the urine, clear and of normal color when passed, becomes of a dark brown and finally black color on exposure to the air. This change in color is produced immediately upon the addition of an alkali, such as a solution of caustic 188 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alcohol soda The addition of a few drops of ferric chloride ,,luti, PM "i\r., « ''I'"' l '" 1 '"' which soon fades, me urine reduces Fehling's solution, a fact which might cause a suspicion of diabetes, but the specific gravity is normal, the fermentation test fails, and the plane of polarization is not deviated. Trine presenting this peculiarity always contains homogentisic, or hydro- quinone-acetic, acid C s H 8 0„ which, though not itself nitrogenous, is derived from the splitting up of the aromatic nucleus of albumin, more especially from tyrosine and phenylalanine. The cause of this con- dition is unknown", but it is doubtless due to some ormality of protein metabolism, analogous to and diabetes. It is seen more frequently in lis and may be intermittent or permanent in its irrence. In some cases it appears to be a familial affection, Osier having observed it in four members of family. It is said to be observed more frequently in cases of consanguinity of the parents. AJcaptonuria is. so far as at present known, a con- in of no pathological significance, being accom- ied by no other symptoms of functional or organic ise. It may. indeed, be present in cases of ochronosis, but is not a necessary accompaniment of this affection. Gouget (La Prcsse Olediccdi . July 20, 1912) has found a number of references in the" literature of the past, to cases of melanuria which . probablv instances of alcaptonuria. Thus Scri- ius (1584), Zacutus, and Lusitanus (1649) describe - of young children in apparent health who passed black urine, and Schenck (1609) reports the case of a monk who presented the same urinary anomaly during his whole life. T. L. S. Alchemy was the immature chemistry of the Middle Ages, characterized by the pursuit of the transmutation of base metals into gold, and the ch for the alkahest and the panacea. Adam, states a medieval legend, was the first alchemist; one cannot say absolutely that the last has not yet heen born, but certain it is that the alchemist still lives, and thrives, indeed, in this twentieth century. This pseudoscience existed in Egypt and India; the Us handed it on to Rome and Constantinople. The rise of the Christian Church, and the fall of paganism, contributed a belief in the warring spirits of right and wrong, and in the constant presence of unseen powers. What was true of humanity was to the medieval thinker true also of non-sentient matter. There was human demonology; and the half-under- Stood chemical phenomena were considered demon- iaoal struggles. Thus was alchemy part and parcel with necromancy, witchcraft, and the black arts. Many of the alchemists of the Middle Ages were also true mystics and followers of the esoteric teachings of ancient Egypt and Greece. Alchemy should have died when Lavoisier in the eighteenth century discovered oxygen and the laws of the conservation of mass. Instead alchemy simply slipped out of scientific society. And yet even to-day chemists are not at all sure regarding the number of elements in matter, or whether there are elements at all; nor are they sure of the impossibility of changing one kind of matter into another. It has oftentimes happened that out of charlatanry comes good; cer- tain it is that out of alchemy was born the modern ile science of chemistry, by which medical science has in turn so greatly benefited. Johx B. Huber. Alcohol. — Ethyl Alcohol; Ethyl hydrate; Ethanol; Methyl carbanol, Spiritus Vini. The term alcohol formerly restricted to grain or ethyl alcohol, but is now used as a generic name for a definite class of bodies. Other alcohols resemble ethyl alcohol in their properties; that is, they contain hydroxy! (OH) in combination with a hydrocarbon radical. The general formula for an alcohol can be expressed by "ROH," where "R" is any aliphatic hydrocarbon radical. When, however, "R" is an aromatic radi- cal, the resulting compound closely resembles the alcohols in its properties, but possess a I e acid character, and is classified under the phenols, the type member of \\ hich is carbolic acid. The alcohols, while not alkaline in character, resemble the inorganic bases in forming salts with acids. The compounds so formed are called esters. Under the influence of dehydrating agents, two mole- cules of alcohol lose ft molecule of water and an ether IS formed. The hydrogen atom of the alcoholic hy- droxy! reacts with some metals, as sodium, and forms alkoxides or alcoholates. With the fixed alkali' , no salts are formed, while the phenols, on the other hand, form definite compounds. Ordinary alcohol, grain or ethyl alcohol, is produced by (1) the fermen- tation of a saccharine body; (2) synthesis in the laboratory. Preparation. — Alcohol is produced by a particular ferment (Torula cerevi&ice) acting upon saccharine sub- stances, causing them to split up into alcohol and carbon dioxide, e.g.: Glucose = Alcohol + Carbon dioxide. C 5 H 12 O a = 2C,H,HO + 2CO, Its preparation depends on the property of glucose (dextrose) to decompose into carbon dioxide and alco- hol in the presence of yeast. On account of the pro- hibitive cost of dextrose, substances rich in starch, as potatoes, grain, etc., are used. After the proper treatment, by which the starting material is converted into a fine pulp, the starch is converted into sugar by an enzyme or acid. The saccharine solution is then fermented by the aid of yeast. The resulting liquid, containing the alcohol, contains also carbonic acid gas, and is known as a fermented liquor. It may be used in this, the carbonated or "sparkling" condition, all t he effects of the alcohol exhibiting themselves, or it may be left until the CO, has escaped; or the alcohol may be distilled off in a more or less impure condition, giving us a distilled alcoholic liquor or spirit. Cane-sugar and milk-sugar undergo a conversion first into glucose and then into alcohol. Minute quan- tities of acetic and succinic acids, also traces of alde- hyde, fusel oil (amyl alcohol), and glycerin are produced at the same time. It is an interesting and important fact that the fermentation gradually ceases as the alcohol produced nears eighteen per cent, strength, and when the latter is reached further action ceases. This is due to the action, on the ferment, of the alcohol itself; the strength named above being just able to precipitate it. In the grape juice, when this strength is reached, if there still be unfermented sugar, a "sweet" wine results; if none, a "dry" wine. When any of the fermented liquors are distilled, al- cohol mixed with water passes over into the receiver. Repeated distillations free it from the greater portion of higher alcohols and water. Its degree of concentra- tion can then be determined by taking its specific gravity and comparing the result with a fixed and official table in which the strength for each specific gravity is worked out. The last amounts of water can be gotten rid of only with the greatest difficulty; as, for example, by distillation over quicklime out of contact with air (from which it rapidly abstracts moisture). In a diluted condition, under the influence of another ferment, alcohol is changed to acetic acid by a process of oxidation; thus, e.g. white wine vinegar is produced. Alcohol C,.H,HO + O, = Acetic acid = CILO, + Water. -f- H,0. Alcohol occurs in commerce and pharmacy in vary- ing degrees of concentration. When absolute alcohol is required, it should be freshly prepared, that of the shops being often only of 98 per cent, strength. IS!) Alcohol REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Absolutely pure alcohol is a colorless, limpid, pleas- antly smelling liquid having a sharp, burning taste; boiling at 7S.5° C. (173.3° F.), and, at 20° C, having a specific gravity of 0.7895. Its affinity for water is intense, even abstracting it from the air when the bottle is not securely corked. If it be mixed directly with water, heat will be produced, the volume of the mixture being less than the sum of the volumes of the components, thus showing that combination has resulted. It is a solvent of great power, advantage of which is taken both in the arts and in medicine, e.g. in the solutions of the fixed active principles of drugs, called tinctures, or the solutions of the volatile active principles, called spirits. It dissolves the alka- loids, essential oils, many resins, some fats, and C0 2 freely. Its distinguishing chemical properties are: (1) its affinity for water, (2) its coagulating power on albu- minoids, and (3) its antifermentative power when stronger than eighteen per cent. Advantage is taken of the first, in the mounting of microscopical sections, to abstract all the water before immersing them_ in the oils and balsams; of the second, in the hardening of the tissues for study and section; of the last, in the preservation in bulk of anatomical specimens, and those medicinal agents which undergo change in other media. Alcohol, U. S. P., is defined as "a liquid composed of about 91 per cent., by weight, or 94 per cent, by volume, of ethyl alcohol, and about 9 per cent., by weight, of water." It has a specific gravity of 0.820 at 60° F. and boils at 7S° C. (172.4° F.). Alcohol Absoluhim , U. S. P., is "ethyl alcohol, con- taining not more than 1 per cent., by weight, of water." Its specific gravity and boiling-point are stated above. Alcohol Dilutum, U. S. P., is "a liquid composed of about 41 per cent, by weight, or about 48.6 per cent. by volume, of absolute ethyl alcohol, and about 59 per cent, by weight, of water." It has a specific gravity of 0.938 at 60° F. Alcohol Deodoratum, U. S. P., is "a liquid composed of about 92.5 per cent, by weight, or 95.1 per cent, by volume, of ethyl alcohol, and about 7.5 per cent., by ■weight, of water." It has a specific gravity of 0.S16 at 60° F. Physiological Action. — The extraneous effects of alcohol are of high importance. By the creation of a partial vacuum upon the cooling of an enclosed space previously heated by burning it, glasses are affixed in cupping. It is a powerful disinfectant, especially antizymotic, being thus one of the best and most generally used preservatives. Its local effects are even more important. Exter- nally, it is cooling by its evaporation, although, if the solutions have a strength of fifty per cent, or more, it becomes a rubefacient, especially if rubbed into the surface, or if its vapor be confined. It is slightly locally anesthetic, especially in relieving itching, and, through the contraction of the vessels by its cooling effect, may locally check perspiration. Its solvent, combined with its disinfectant and stimulant proper- ties, render it a useful lotion for cleansing diseased surfaces. If, however, the solution be strong, it acts rather as an irritant, and, by the abstraction of water, and the partial and temporary coagulation of the albumen, as an astringent. It acts very promptly upon mucous surfaces, being, as upon denuded tissues, stimulant to irritant and more or less astringent. Its presence in the mouth stimulates the secretions, not only of the mouth, but of the stomach. Even a few drops applied at the base of the tongue have been seen to produce an almost immediate flow of gastric juice. The intellectual functions are thus reflexly stimulated also, though later, by direct contact with the cells, the opposite effect is produced, upon both the salivary glands and the brain. If held in the mouth, it produces a numbing effect. Small quantities of alcohol, properly diluted, taken into the stomach, produce an agreeable sensation of warmth. A turgescence of the capillary plexus of the mucous membrane occurs, which is speedily followed by a free secretion from the gastric follicles due, in all probability, to (a) the increased supply of blood, and (,3) the stimulation of their glandular orifices. The movements of the stomach, as well as its secretions, are increased, and absorption of the products of digestion is greatly hastened. It is therefore one of our most powerful stomachics and digestive stimulants. These effects are not lost upon the absorption of the alcohol, but appear, upon the contrary, to be still further increased by its presence in the circulation. Its presence, however, in any considerable quantity in the food mass inhibits pro- teolysis, while in concentrated form it acts rather as an irritant, and its favorable action upon digestion is wanting. The direct irritation may result even in vomiting. Continued concentrated doses tend to produce chronic gastritis and gastric catarrh. More- over, the continued recourse to this artificial aid to digestion tends to necessitate it, and in increasing degree. Larger and larger amounts are apt to be required, and the natural powers of digestion be- come permanently and seriously impaired, and at length may be almost completely lost. Aside from the effects upon digestion already described, the action of alcohol in the stomach is one of reflex stimu- lation of the heart and of the respiration, provided t hat the drug is not too much diluted. In the intes- tine, peristalsis is directly stimulated, and an astrin- gent effect produced. Alcohol is very promptly absorbed, and circulates as alcohol, in which form it comes into contact with the tissues and exerts its peculiar activities. The liver, being the first to receive the blood freshly charged with alcohol, in a more concentrated con- dition than after dilution by the general circulation, is the first to feel its stimulating effect, and the first to undergo pathological changes. The liver cells are stimulated, and as a result we have an increased flow ofbile. Later, the cellsenlarge and become infiltrated with fat globules. The stronger drinks, particularly if taken undiluted, and if the practice be persisted in for any considerable period, cause an irritation of the connective-tissue cells in the liver surrounding the portal radicles. A proliferation of the same occurs, and, as a final effect, contraction of this newly formed tissue — as is the case with all newly formed connective tissues— ensues, producing the so-called cirrhotic or hob-nailed liver. With the primary new formation there is naturally an increase in the size of the organ, while the secondary contraction causes an atrophy of the liver cells, (a) by direct pressure, and (,.)) by diminishing their normal blood supply. In I countries where the more dilute alcoholic drinks (wines and beers) are the national beverage, cases of cirrhosis are unusual; while the contrary is true whi n the more concentrated drinks (brandy, whiskey, gin, or rum) are largel} r consumed. Finally, the portal radicles become so narrowed by the contraction of tlie connective tissue in which they lie that the portal circulation is interfered with, thus producing a mechanical congestion of the intestinal, peritoneal, and gastric capillaries, with ascites and watery stools. Kidneys. — The alcohol being in a much less concen- trated condition on reaching the kidneys than is the ease with the liver, the effects, both physiological and pathological, are less marked. The watery portion of the urine is increased; the solid, at least so far as urea is concerned, is diminished. The increased amount of water excreted is a natural result of the increi blood pressure; the diminution of urea is due to the lessening of oxidation of the nitrogenous tissues. In these organs, although, the irritating results manifest themselves more slowly than in the liver, they occur in an exactly similar manner. Bright's disease is thus frequently induced. 190 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ah nliiil I ]„■ effect of alcohol upon the skin is moderately to ncrease perspiration. 'I his is a natural result of the •utaneous turgescence, but it is not known whether here is also a direct stimulation of secretion. I he temperature of the skin is temporarily raised I v his turgescence, and the nerve endings are thus vanned. There is thus a false impression of warmth created, the general temperature actually falling liiiekly, and the individual being especially exposed o the evils of cold, tn chronic alcoholism there is apt , be interstitial thickening of the integument. Systemic Effects. — In spite of the great amount of i which has been concentrated upon the investi- gation of the systemic effects of alcohol, our con- clusions arc doubtful to a greater extent than in the ol almost any other drug. There seems to be room for question as to the ultimate net results, ml a great deal of it as to the modus operandi. The ndications are those of a drug which for a very brief id stimulates, then depresses the tissues upon ii it acts. As to the depression, there is nowhere question, but it is claimed by high authority that, nit for the reflex stimulation already noticed, its effects ipon the nervous system are wholly depressing, the irent stimulation resulting from depression of the bitory and controlling functions. Undoubtedly his weakening of will power, and of the higher unctions of coordination, plays a very important part : i lie apparent manifestations of stimulation, and nuts for the great lack of uniformity in them in lifferent individuals; yet it does not seem possible to nit so well in any other way for the symptoms i^ by assuming the existence of a primary stimulation. practical study like the present, it seems more irofitable to discuss the conspicuous net results, and ■ id extended discussion of the mechanism. Thi> peculiar interaction between the effects of deohol upon the circulation and those upon the ous system renders it difficult to consider either without having first taken up the other. As a result of the systemic effect of alcohol, the rate, md to a greater extent the force, of the heart, are eased, and this sufficiently to increase the blood -lire, in spite of the fact that there is marked ial dilatation. This period is followed by one of lepression, and the first stage is shorter, even almost altogether wanting, in proportion as the dose is increased. How far this result is due to depression of inhibition is one of the questions of greatest dissension among physiologists. The same observation of an increase in respiration, and the same dispute as to its cause, are to be re- corded. In any case, it seems clear that the result is nut due to any direct central stimulation. The chief nervous effects of alcohol are upon the brain, especially upon the cerebrum. Its action is delirifacient, there being a preliminary period of stimulation running into excitement. Even this stimulation is a narcotic one, being unequal, and resulting from the first in an interference with equilibrium. It is because this increased activity is due largely to inhibition of the powers of self-control and restraint that the claim has been advanced that this is the sole cause, and that alcohol does not directly stimulate at all. It is quite evident, however, that such a result would necessarily follow the increased cerebral circulation due to general circula- stimulation, even if there were not, as there appears to be, a direct primary stimulation of the rebral cells. Only at the very beginning are the mental processes quickened, but after they have become slowed and blunted, the individual still be- lieves them to be greatly improved. Despondency and mental pain are thus decreased, but the subject loses his judgment and becomes talkative and other- wise demonstrative and self-asserting. Intellectual, followed by sensory and motor paralysis then comes on, and the coma stage follows that of delirium. Paralysis of respiration and particularly of circulation may become complete, resulting in death. During the stage of depression, vomiting of central origin usually appears. Alcohol is itself Oxidized as a food, but decreases tissue oxidation. This may to some extent account for the reduced temperature, though this is chiefly due to the increased heat radiation resulting from engorgement of the superficial vessels. It is more rapidly oxidized under the influence of exercise, exposure to cold, and in fever, 'this is regarded as the normal method of its elimination, only five or ten per cent, ot it being excreted by the kidneys and lungs as alcohol, it is believed that this nutrient function does not at all relieve the demand for nitrogenous nutriment, but may to a great extent supply that for carbonaceous. The latter fact explains the accumulation of fat in alcoholic subjei though their obesity is also favored by the decreased elimination of water which finally takes place. The remote effects of alcohol may be good, but are far more likely to be harmful, due to excessive use, or to use continued beyond the period required. The general rule should be to use alcohol only temporarily. If used only to the extent of stimulating the digestion, it can result in great improvement of nutrition. But it may result in the complete destruction of digestion. If properly proportioned as to dosage, it is an excellent food in fever, but it may be used so as to exhaust the; system. It can be used to benefit the excretory processes of skin and kidneys, but it may destroy cither or both, resulting in cutaneous hypertrophies, or in nephritis. It is very apt to induce obesity, partly by interfering with the elimination of water, ami partly by checking the oxidation of fat. It has a tendency to destroy fine cell structure everywhere. This is specially seen in the destruction of the finer moral and intellectual functions, in sensory and motor paralysis, and in reducing the parenchymatous liver tissue, with an increase of its fibrous portions. A peculiar kind of mania is induced by it, known as delirium tremens, chiefly characterized by hallucina- tions and delusions of snakes, demons, and other terrifying subjects. This appears to be connected with some peculiar form of malnutrition, as it never appears until after the loss of appetite has become pronounced. The ability of the system to withstand exposure, fatigue, or disease is slowly but most surely destroyed by alcoholism. This is especially noticed in pneumonia, which is almost certainly fatal to drunkards, although alcohol is one of the surest reliances in supporting pneumonic patients who have not been addicted to its use. Fatal acute poisoning by alcohol is not unknown, the effects pertaining espe- cially to respiration in some cases, to circulation in others. Various accidents are frequently mistaken for intoxication, especially apoplexy, coma from blows upon the head, and opium poisoning, and many scandals have originated from wrong diagnoses. The greatest care should be taken in the differential diagnosis of these cases. Therapeutic Uses. — The therapeutic local uses of alcohol are sufficiently indicated by our account of its local effects. Its uses as a digestant are undoubtedly its most important ones, if we regard the frequency of employment. Here the method of administration is of the utmost importance. It should not be used when any inflammation or irritation of the stomach exists. The smallest, possible dose consistent with effectiveness should be employed. A teaspoonful to a tablespoon- ful of brandy or whiskey should suffice. The strength as imbibed should not be greater than five to fifteen per cent. It should be taken quickly just at the beginning or during the early part of the meal. If taken too soon, the effect is lost, and the liver may suffer. If taken too late, it interferes with digestion. Diluted alcohol is preferable to liquors, if one regards 191 Alcohol REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the danger of forming a habit. The administration should be carefully watched and skilfully controlled, and an effort made to decrease the dose almost from the beginning, and abandon it just as soon as possible. This is not only to avoid the formation of drinking habits, but to avoid inducing the stomach to depend upon the artificial stimulus. Its next most important use is as a food. This may be at such times as ordinary food is not desired or not borne, but when food is imperatively required. It may then be taken by the stomach or the rectum. It will often aid in the digestion and assimilation of milk, besides contributing its own portion of nutri- ment. Therefore a milk punch is one of its most use- ful forms, but one of the most dangerous as to habit. In fever, it is useful in one, injurious in another class of cases. In a typical case, it should not only nourish the patient, but calm him, and reduce the fever. If the opposite effects are induced, it should not be used. Alcohol is a fairly good carminative, and brandy is astringent in many cases of diarrhea; it is very difficult to say why. Insomnia may be relieved by alcohol, though there is a tendency to require its continued and increasing use, and this should under no circumstances be permitted. Gin is an excellent diuretic, but the alcohol plays probably a subordinate part. Alcohol, if taken in full dose and very early, espe- cially with an abundance of water, is most valuable in breaking up an impending cold. It is readily conceivable that the most disastrous results may be thus avoided, when we consider the consequent trans- fer of blood from the viscera to the skin. The effect of the alcohol must in such cases be promptly sup- plemented by warm external applications, or at least protective coverings. Alcoholic Liquors. — The various forms of alcohol can profitably be here considered, rather than to take them up in their regular alphabetical order in the different parts of this work. The alcoholic liquids of the different classes are as follows: Kumyss is the weakest of all in alcohol. It is simply fermented milk. Mare's milk was originally used, but it is now very often substituted by cow's milk variously modified. It was originally fermented by the action of a special ferment, but yeast is now generally employed. It should be used while fresh, never more than four or five days old. It should con- tain about one and a half or two per cent, of alcohol, and be strongly carbonated. There are also traces of unknown ethers developed in the fermentation. It is estimated to contain about twelve per cent, of solid nutriment. It is soothing to the stomach, without in any degree retarding digestion. Its primary stimulating effect is followed by a slight soporific tendency. Beer, Stout, Ale, and Porter are made from barley, the starch being first converted into sugar by the action of the diastase, under the influence of heat and moisture. In this condition it is Malt. The malt is subjected to a vinous fermentation. In making beer, this is done slowly at a low temperature'. in the others more quickly, at a high temperature. The darker-colored stout and porter are made so by a partial burning of the materials. The percentage of alcohol ranges from two to nine, ordinarily about four or five. These liquors are abundantly carbon- ated and they contain more or less digestible nutri- ment. They appear also to exercise a small amount of digestive effect upon some foods. Hops or lupulin are added to genuine beer, but a great variety of bitter substances are in use, many of them selected without the slightest regard to their injurious effects upon the system, so that beer, if prescribed, should be always of a brand of known composition. Various other seeds, especially rice and peanuts, are similarly used, as well as many other starchy sub- stances. Some savage tribes are ahead of us, in that they use substances which contain distinct medici- nal constituents, together with the alcohol-yielding portion. Wine, Cider, Pulque. — These are fermented vege- table juices, wine from the grape, cider from the apple, and pulque from the century plant. If used while still in the carbonated state, they are called "sweet" or sparkling, otherwise they are "hard" or " dry." In addition to the carbonic acid and alcohol, there are considerable amounts of sugar. When this amount is large, they are specially called "sweet." There are also considerable amounts of tartaric and acetic acids. When this is the case the wines are called "sour." A variable amount of tannin is present in red wines. Wines which have had the percentage of alcohol artificiallj- increased, as port and sherry, are called "heavy" or "fortified ". Vinum Rubrum, or Red Wine, U. S. P., is made from the entire grapes. Vinum Album, or White Wine, U. S. P., is made from grapes from which the skins, seeds, and stems have been removed. Each contains from ten to fourteen per cent, of alcohol. A very large number of sugary fruits are utilized in the manufacture of special wines. Distilled Spirituous Liquors. — Any fermented alco- holic liquor may have its alcohol distilled off. In this process various other substances are certain to come away with the alcohol, and their complete re- moval is very difficult, so that each kind of spirit will possess its characteristic color, odor, and taste. For the most part, however, these associated matters have not a high degree of physiological importance. Medicinally, the liquors are used chiefly for their alco- hol, and there is little choice among them. The physi- cian's responsibility in prescribing brandy, whiskey, and other pleasant forms of alcohol, and thus tending to promote alcoholic habits, is very great. In most cases, dilute alcohol or diluted deodorized alcohol, variously admixed so as to obscure its character or to make it less palatable, can frequently be employed with equal advantage. Because this is now so gen- erally done by the more cautious class of physicians, and as there is so little genuine prescription demand for brandy and whiskey, it is seriously proposed to drop them from the Pharmacopoeia. Spiritus Yini Gallici, or Brandy, is distilled from wine, and contains thirty-nine to forty-seven percent., by weight, of alcohol. There must be no admixture or modification of any kind, and it must be at least four years old. With the ordinary properties of its alcohol, it combines a distinctly astringent effect upon the bowels. Spiritus Frumenti, or Whiskey, U. S. P., is similarly distilled from the fermented product, "mash," of grain, either rye or corn (the latter " Bourbon Whis- key"), or mixtures of them. It should be at least two years old and contain from forty-four to fifty per cent, of alcohol. Gin is the equivalent of the compound spirit of juniper, elsewhere considered. Upon keeping spirituous liquors, various ethers de- velop in them, which tend to make them pleasanter to the taste, but which do not materially modify the action of the alcohol. The principal impurity of alcohol, especially of whiskey, is fusel oil, or Amylic Alcohol, next considered. Amylic Alcohol. — Fusel Oil; Grain Oil; Potato Spirit Oil. (C,H„HO.) In speaking of the alcoholic liquors, reference v i made to fusel oil as one of the commonest of impu- rities. It can be obtained from all crude alcoholic liquids, and is removed from them in purification. It is chiefly obtained during the later portions of their distillation, and is much more abundant in spirits obtained from some sources than from others, notably from potato spirit. It is considerably heavier than 192 REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Alcoholic and Drue Intoxication pure ethyl alcohol (specific gravity 0.818) and its boiling-point (128 130 C.) is very much higher. It has an oily consistency, is colorless, has :i powerful odor and a burning, acrid taste, the inhalation caus- ing headache. Although amylic alcohol has very powerful physiological properties, it has never been b utilized in medicine, and it is used chiefly solvent in manufacturing operations. It is a very , -rf ul poison, the symptoms being those of great iression. Mi:tiiylic Alcohol. — Methyl Alcohol; Wood Al- Spirit; Wood Naphtha; Columbian Spirit; Pyroiylic Spin!. ( (II .< > II.) In the crude pyroligneous acid distilled from wood '.c Acid) there is about one per cent, of methyl ihol, which is obtained by light distillation, after iddition of lime, and is then purified. It comes first in the series of alcohols, that is, it is the simplest of them. It has been found somewhat sedative, es- pecially to the cough of consumptive patients, in s of 1 to 3 c.c. (15 to -15 minims), yet it can t-lv be regarded as a medicinal substance. As it cannot" be used as a beverage, ten per cent, of it is added to alcohol in England, to allow of the use of the latter in the arts without danger of defrauding the customs laws relating to spirituous beverages. This mixture is known as Methylated Spirit. Methyl alcohol is excellent for burning purposes, owing to its large percentage of carbon, and isrelatively very cheap. Denatured Alcohol. — In 190f>, a Federal law was en- acted, providing that domestic alcohol may be with- drawn from bond without the payment of the internal revenue tax. for use in the arts and.industries, and for fuel, light, and power, provided it shall have been mixed in the presence and under the direction of an authorized Government officer, with methyl alcohol or other denaturing material which is destructive of its character as a beverage and which renders it unfit for liquid medicinal purposes. By a subsequent amendment, it was specified that such alcohol can be used in the manufacture of definite chemical sub- ices, when the alcohol is changed into some other mical substance and does not appear as alcohol in the finished product. The denaturing material employed may be either ten parts of methyl alcohol and one-half part of ben- zene to one hundred parts of alcohol, or two parts of methyl alcohol and one-half of pyridine basis. The characters of the methyl alcohol and pyridine basis to be employed are specified, as are all other condi- tions and regulations, in a pamphlet of 169 pages issued by the Internal Revenue Department. Toxicology. — The internal use of wood alcohol is most dangerous and even its application externally should be discouraged. So small an amount as a poonful has produced serious results, as has ab- sorption through the skin, notwithstanding that it is often applied in this way with impunity. Serious results nave also followed its free inhalation. The poisonous effects are much like those of formaldehyde. There is great irritation of the mucous surface, fre- quently with severe vomiting. There is headache, mostly frontal, with a sense of pressure, pain and soreness of the eyeballs; later, usually from the second to the fourth day, there are disorders and then loss of vision. Sometimes this first failure will be followed by apparent recovery, but total blindness almost certainly supervenes. Very large doses may result in prompt and fatal depression following an initial period of irritation. Most cases of poisoning by wood alcohol have resulted from its fraudulent use in liquors, medicinal preparations and flavoring ex- tracts, and most of the States now have stringent laws against its use. Very little can be done in the way of antidotal treatment, though the early use of pilocarpine has sometimes resulted favorably. Henry H. Rusby. Vol. I.— 13 Alcoholic and Drug Intoxication and Habituation.— I he role that alcohol plays in the production of psychoses, while admittedly an important one, is not at all well understood. Recent statistics, con- servatively interpreted, would indicate that about twelve per cent, of the insane confined in public institutions in the United States are there because of its influence, direct or indirect. When, however, the multitudinous ways in which alcohol may enter as a factor in the production of mental disease and the far-reaching effects it produces are considered, it is readily seen that do statistical study can begin to fathom the problem. While the psychoses considered under this heading clo.-ely associated with alcohol and in the main present fairly constant and characteristic pictures, it must not be forgotten that alcohol may enter as an etiological factor in the production of symptoms ordinarily considered to be quite distinct from the alcoholic psychoses properly so called, such as the manic-depressive and dementia precox psy- choses, while it is considered by some to be a very important causative agent in paresis. When attacks of these psychoses are brought about by alcoholic indulgence it is probable that they are considerably modified and as a result present a somewhat atypical picture. That the psychoses produced as the result of abuse of alcohol are dependent, in the last analysis, upon something besides the alcohol, namely, upon some peculiarity of make-up of the individual, is well shown by the fact that while a history of abuse of alcohol is frequent in cases admitted to hospitals for the insane, it is rare to find at autopsy what in general hospitals is considered so typical of alcoholism, namely, cirrhosis of the liver. This means that the locus minoris resistentiae in these cases is the brain and that mental disease supervenes before the liver becomes involved. Psychology. — Alcohol has long been supposed to be a stimulant. Such supposition, however, was based largely upon false interpretations of subjective experiences. For example, one feels rested from fatigue by a small dose of alcohol. The rested feeling was supposed to be due to stimulation. On the contrary, it is due to inhibition in the sensory channels conveying the sense impressions that make up the feeling of fatigue. It has also long been supposed that small doses of alcohol produced an increase in the power of muscular work and an increase in efficiency in the performing of simple mental tasks. This stimulation was sup- posed to continue for twenty minutes to one-half hour. The recent work of Rivers and Webber indicates that such small doses produce no effect whatever. If they are correct alcohol then remains a depressant and paralyzant from the first without any effects of stimulation whatever. The types of persons who drink and the reasons for drinking are many and varied. While there are certain social factors involved, the more important of the conditions lie in the make-up of the individual. First, we have the cases in which the drinking is the expression of a psychosis and in no wise its cause. Here we find especially the early cases of paresis and the mild cases of manic-depressive psychosis. The alcoholic symptoms may completely cloud the picture for some time. Second, there is a considerable group, to which belong those who drink "to drown their troubles," who attempt to escape from reality by introducing a veil between it and them, by making themselves less accessible to the world of reality by dulling their sensorium. This class is composed of hysterics and members of that large group of psychasthenics. It should be remembered that the expressions of their difficulties are often periodic and that it is generally upon such a groundwork that dipsomania is founded. 193 Alcoholic and Drug Intoxication REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Third, there is a considerable group who are especially susceptible to alcohol and although not consuming large quantities manifest an exaggerated reaction to small doses. Here we have especially the post-traumatic constitution — cases following head in- jury and sunstroke — and arteriosclerotic and senile cases. These are the unresistive types and alcohol, like fever, proves to be a measure of their resistance and stability. Fourth, we have alcoholism entering into, compli- cating, and modifying the picture of other psychoses, particularly dementia pracox. Not infrequently praecox cases are supposed to be alcoholic in their early stages because of the prominence of the alcoholic features. Finally, there appears to be a certain number of purely alcoholic psychoses — that is, psychoses de- pendent upon alcohol per se. Of these psychoses those clearly dependent upon the effects of alcohol are the states of acute intoxication, including patholog- ical drunkenness, while delirium tremens, alcoholic hallucinosis, Korsakoff's psychosis, and the chronic alcoholic psychoses are dependent upon long indul- gence, and whether they are directly thefurt her ex- pression of chronic alcoholism or are in some way dependent upon the secondary elaboration of toxins the result of disordered nutrition, they certainly need something besides the simple ingestion of a toxic dose of alcohol. Kraepelin proposes to call them, after the manner of the psychoses due to syphilis, the meta-alcoholic psychoses. Drunkenness. — The phenomena of drunkenness are, from the first, phenomena of paralysis. In the early stages it is only the higher psychic functions, which are largely inhibitive, that are affected, so we get apparent stimulation in the excitement produced with flight of ideas, pressure of activity, loss of the sense of propriety, degradation of the moral tone, and loss of power of voluntary attention. The lower centers then become paralyzed and then appears muscular incoordination, manifesting itself first in the hands and facial muscles and the muscles controlling articulation, the speech becomes thick and the gait unsteady. Sensory disturbances appear, such as diplo- pia, tinnitus aurium, and the senses of touch and pain are blunted. If the paralyzing action of the alcohol continues, coma results which may be fatal. The mood during intoxication may be a pleasant one, and frequently is one of boisterous exaltation, consti- tuting the exalted type; on the other hand, a sad, depressive, lacrymose mood may prevail, constituting the depressed type. Pathological Drunkenness. — Among certain predis- posed individuals alcohol produces unusual and much more severe symptoms. In this condition we may find hallucinations and delusions dominating the field of consciousness, the delusions being usually of a per- secutory character. In other cases the excitement may issue in a wild, maniacal frenzy or the depres-ion may be so profound as to result in attempts at suicide, In some persons the paralyzing effects of alcohol are unusually pronounced and coma appears early on the scene. Those who have latent hysterical tendencies may have hysterical attacks during intoxication, while alcohol frequently produces convulsions in epileptics. Aside from this latter action, however, the convulsive properties of alcohol alone are capable of producing convulsions in persons who have long in- dulged and are profoundly degenerated, though this is disputed by others who claim that such individuals must have been of epileptogenic make-up. In these cases of pathological drunkenness in which the reaction to alcohol is so pronounced, it is quite common to find amnesia for periods of profound intoxication. Delirium Tremens. — This disorder usually occurs as the result of a prolonged drunken debauch in a chronic alcoholic, during which the patient has had insufficient food and rest. According to some authors it may result directly from the withdrawal of alcohol'. It may, however, appear in the moderate but continu- ous drinker as the result of a single excess, following a traumatism, or as the initial symptom of an acute illness. The whole question of the occurrence of an absti- nence delirium is a mooted one. The recent researches of Holitscher on this point are illuminating. The conclusion appears to indicate that abstinence delirium if it occurs at all is extremely rare. Care must be taken in reaching a conclusion to eliminate as possible causes, wounds, infectious diseases, psychic shocks, operations, etc. We must remember also that in many cases the delirium has had a prodromal period of a number of days, and that one of the symp- toms of this period is a disgust for liquor. The delirium, therefore, occurs in spite of, not because of abstinence. The disease may appear suddenly, but there is generally a prodromal period during which the patient is nervous, with coated tongue, suffering from anorexia, restlessness, tremulousness, disturbed sleep and insomnia. This condition rapidly advances with the onset of the attack, the characteristic symptoms of which are rapidly developed. They are tremor, delirium, and albuminuria. The tremor involves more particularly the small muscles of the hand, face, and tongue, but may also affect the entire musculature. It is increased by muscular tension, such as forcibly spreading the fingers apart. The delirium is an acute hallucinatory confusion. Disorientation is often quite complete, the patient, although perhaps fastened in bed, believing himself in his office or home, surrounded by familiar faces. The predominating hallucinations are visual and charac- teristically take on the form of animals. The patient sees all sorts of horrible creatures, snakes, rats, mice, alligators, etc., which are uniformly in motion. Surrounded by the loathsome creatures and by hor- ribly grimacing faces, terrified by screams and shrieks (auditory hallucinations), he presents a picture of abject terror. In addition to these symptoms, the patient may complain that insects or worms are crawl- ing under his skin (paresthesia) and mistake spots upon the bed or walls for bugs, mice, etc. (illusions). At the height of his excitement the patient is in con- stant motion, picking insects from his night-die--, repelling the approach of terrible animals; in the extreme frenzy of his fright, he may make murderous assaults on those about him, believing them to be his enemies, or perhaps attempt his own life to escape from his horrible surroundings. During all this time the patient is constantly talking, shrieking in fear at I times, at others carrying on an incoherent discourse with imaginary persons, fragments of which often relate to his former occupation and friends. The character of the delirious experiences varies greatly. One patient left the house in his m clothes and went a distance of several miles attired thus to the house of his sister. On reaching there lie told them that his father and some Chinamen \ going to kill him. Another patient came to the hospital with the history that he suddenly became disturbed one night and told his wife that he saw a troop of darkies dancing in his bedroom; they appeared to be rehearsing a play; he saw a strange man of giant stature jump off his bookcase into his wife's bed. He tried to chase these strangers from the room, and as they vanished he could see the skirts of the women and the heels of the men flitting past the doors; they would invariably return; their faces mocked him. Some patients do not present this picture of ex- treme restlessness and the pressure of activity is not communicated to such a degree to the function of speech. Such patients may present an alert appear- ance, be fairly calm, and can often be taken in the lecture room before the class. 194 iiKi i:i:i:\n: handiwidk 01 tiik medical sciences Alcoholic and l>niu Intoxication The mood, ton. may be quite different ; instead of be- ing in a condition of constant apprehension and tear of an overwhelming and terrifying environment, they may be calm, interested, and amused by their delirious experiences. The patient quoted above on his second day i" the hospital was highly entertained by the iearance in the ward of a man with a monkey's \ walking aliing the floor in a barrel, the bottom hich had been knocked out. Then there was the "human ironing board." This was a man's head I to an ironing board on wheels; the man spit icco juice a fiout the floor and water squirted from eyes. The patient was much amused by these riences ami told the doctor how he loved to lie ed anil watch it come and go. He thought these two monstrosities the property of the government that they were intended for the amusement of the nts. Another patient saw flocks of partridges about his D ami a turkey an inch high on his window sill. spiders and thousand-legged bugs came crawling on bed. These hallucinations produced no surprise lisgust. He merely cited them as of passing ■rest while talking. His aunt's face was lying • to him on the bed, and he tried to kiss it. An- er patient in the hospital saw about him numerous of Lilliputian dimensions anil displayed the liveliest interest in these strange little people. Often dreamy hallucinations and delusions relate igether to his occupation and the patient busies himself with his usual pursuits — occupation delirium. Physically he is in a condition of acute exhaustion. The pulse is rapid and of low tension, the temperature normal or only slightly elevated (occasionally high, the febrile delirium tremens of Magnan), the body id in a profuse perspiration and constantly agitated by muscular shocks and tremors. Occa- ally one sees cases ushered in by all the typical prodromal symptoms, sweating, atonic dyspepsia, restlessness, tremor, precordial distress, anxiety, and disturbed sleep, which do not proceed to the typical lition of mental confusion with multiform halluci- nations. This is the so-called abortive type, the : in sine delirio of Dollken. During the course of the disease almost any cxperi- ee the patient may have, any impression made upon his sensorium is woven into the warp and woof of his d ilirious experiences — sensory flight of ideas. Hallu- cinations seem to arise spontaneously or are easily produced by pressure on the eyeball or merely by L r ning the patient to look at a blank piece of paper. Paraphasia and paralexia are commonly present. Albuminuria is found in a considerable proportion uf cases, probably considerably over fifty per cent., .luring the early stages. At the height of the delir- ium leucocytosis has been found. It must not be for- gotten, too, that here, as in acute toxic states gener- ally, a sluggish reaction of the pupil to light and even complete Argyll-Robertson pupil may be found. This sign disappears, however, on recovery. This is an important fact to be borne in mind in the matter of diagnosis. Acute cardiac dilatation may develop at the height of the disease. Course and Duration. — The psychosis runs an acute course of about three days and terminates in recovery in the majority of cases.* The delirium usually ends in a long sleep. About ten to fifteen per cent. die. Potliology. — Degenerative conditions are found in the central nervous system — acute degenerations of the ganglion cells, and recent hemorrhages. The ganglion cells are found shrunken and there is increase in the glia and some vascular proliferation with slight round-celled infiltration. There may be a chronic leptomeningitis and some narrowing of the cell layers of the convolutions. Changes are also found in the cerebellum. The alterations in the Purkinje cells are supposed to be correllated with the motor symp- tom — tremor and ataxia (Kraepelin, Allers). Wassermeyer is of the opinion that the pathology indicates that the delirium results from an increase in the chronic alcohol poisoning rather than a metabo- lism poison. Chronic Alcoholism. — The effects of chronic alcohol poisoning arc exhibited in every organ of the body) mure particularly the central nervous organs, stomach, pancreas, liver, kidneys, and blond-vessels, and give rise to characteristic symptoms as a result, the most prominent of which are tremor, gastric catarrh, arteriosclerosis, albuminuria, and progres- sive mental cnfeebleinent. The effects on the nervous system are shown in disturbances of sensation, motion, and the intellect. The sensory disturbances arc paresthesia (prickling, tingling, formication), hyperesthesia, and hyperal- gesia. The sensory disorders of the special senses involve principally the eye and ear, producing illu- sions and hallucinations, muscie volitantes, photopsia, amblyopia and amaurosis, diminution of the acute- ness of hearing with the production of subjective noises (hissing, ringing, roaring, etc.), due to middle or internal ear disease. The motor disturbances are tremor, spasms and cramps, epileptiform attacks, and general motor en- feeblement. The mental changes are gradual and progressive, the intellect is obtunded, the judgment overthrown, the moral sense blunted, and mendacity appears in its most bizarre forms; delusions may develop, the most characteristic of which is of marital infidelity and jeal- ousy, and the patient sinks gradually into a condition of permanent mental enfeeblement. Diagnosis. — Alcoholic dementia is to be differen- tiated from other dementias largely by the history. Alcoholic dementia will have a history of progressive mental enfeeblement closely associated with alcoholic indulgence. Graeter has recently called particular attention to the association of alcoholism and dementia precox. Many of the cases of mental deterioration associated with over-indulgence in alcohol will be found to be true cases of precox in which the alcohol is only an incidental and associated feature. Alcoholic Psbudoparesis. — On a groundwork of mental enfeeblement the alcoholic may develop a true expansive delirium which, combined with the signs of alcoholism (ataxia, speech defects, tremor, pupil- lary anomalies, and muscular weakness), may make the distinction from paresis difficult — alcoholic pseu- doparesis. This similarity to paresis is noticeable even when the expansive delirium is absent in cases in which the mental reduction is marked, but be- comes greatest when the symptom complex above outlined is ushered in by epileptiform attacks. Diagnosis. — The distinction from true paresis can usually be made. Pupillary inequality is more com- mon and the permanent results of apoplectic insults (hemiplegia, aphasia) are more often found in the alco- holic form than in the true. The results of polyneu- ritis should be looked for and if found suggest alcohol- ism. The most reliable differential sign is found in the course of the two maladies. True paresis is pro- gressive, tending toward ever-increasing degradation, while in the alcoholic form removal of the poison re- sults very shortly in a remission of all the symptoms, even, in some cases, amounting to a recovery. The symptoms, however, reappear subsequently if drink- ing habits are returned to. It must not be forgotten that an Argyll-Robertson pupil may be transiently present. It is an open question whether both this sign and the whole pseudo- paresis picture may not be dependent upon the pres- ence of syphilis. Alcoholic Epilepsy. — As a result of chronic alco- holic toxemia, the symptoms of which are marked 195 Alcoholic and Drug Intoxication REFERENCE HANDBOOK OF THE MEDICAL SCIENCES throughout by their explosive character, it is not strange that actual convulsions, alcoholic epilepsy, should complicate the morbid picture. These con- vulsions, so far as their individual characteristics are concerned, are indistinguishable from true epilepsy. Occurring, however, in a person beyond the period of adolescence who is addicted to the immoderate use of alcohol, their origin should be suspected. The diagnosis is made clear if they cease upon the with- drawal of alcohol. As this sometimes does not occur the diagnosis can be made only by excluding the causes both of true and of symptomatic epilepsy other than from alcohol. Alcoholic Hallucinosis. — This psychosis may come on suddenly in a chronic alcoholic, as the result of an unusual excess, or it may be of gradual evolution. It is sometimes preceded by one or more attacks of de- lirium tremens. It is characterized by hallucina- tions, auditory predominating, thus contrasting strongly with the predominance of the visual hallu- cinations in delirium tremens. The delusions are of a persecutory nature, in which the sexual element is frequently prominent, and show a tendency to systematization. The system, how- ever, is of rapid growth and loosely organized. Whether of sudden or gradual onset, the first symp- toms are hallucinations, with which persecutory delusions are intimately bound up. The patient hears voices making all sorts of inimical remarks, tell- ing him that his children are not his own, calling him an onanist, reviling or threatening him. In every way his persecutors annoy him by their malign com- ments. Visual hallucinations are rare. Hallucina- tions of smell and taste are not infrequent. The au- ditory hallucinations, quite characteristically, tend to fall into rhythm with outside sounds, as, for example, in one of my cases, the humming of a dynamo. The delusions of this state harmonize well with the hallucinations. The patient is persecuted by invisible enemies who inject noxious vapors in his room at night, poison his food, draw off his semen, and pro- duce nocturnal pollutions. One patient heard voices of enemies whispering at the windows; they were going to kill him, called him a variety of unpleasant names and accused him of all sorts of crimes. The patient attempted suicide. He gave a history of being troubled with noises in his cars for a considerable time, resembling the click of a telegraph machine. When he was drinking these noises became voices. Another patient thought he heard different people talking about him, cursing him, and calling him vile names. Then later he thought he heard his thoughts repeated. While on a drinking bout he wandered about aimlessly, felt that he was being pursued, and heard threats made against him. He bought a knife and walked into the water. In the hospital he heard his old friends accusing him of sexual perversions, pederasty, etc. He told of having heard his associates say, " He is no good; we will get him out of the army," and " He is a sucker for fixing a horse instead of allowing the veterinary to do it," etc. Another patient, a sailor, had been drinking heavily while on shore. When three days out at sea he began to hear threats against him. He heard the men say that they would kill him, they would cut his heart out, and cut him into 50,000 pieces. On the evening of the third day he could stand it no longer and thinking that he saw land ahead he jumped overboard. Grandiose delusions do, however, occasionally occur though they are not sufficiently controlling to modify the picture in any essential way. A case cited by Mitchell shows how they usually manifest themselves. In this ease, in the midst of an active hallucinosis, during which the patient was constantly hearing voices coming from the air and out of the floor, and the passing trains were whist ling his name, and while he saw faces staring at him from the walls, he had an episode during which he assumed chaTge of affairs gave orders, and threatened with death the doctors who refused to obey. Bonhoeffer reports only one case with grandiose ideas, which, however, were only of temporary duration, during the course of an hallu- cinosis with auditory hallucinations of a distinctly threatening character, and one case in which the patient heard music, but otherwise had disagreeable hallucinations. In this state the patient is depressed, apprehensive, often fearful of impending danger, may have anxious and angry states, and often reacts by attacking his supposed persecutors. Throughout this condition the patient is well oriented and consciousness is clear. Some of these cases run a long course and become chronic. Diagnosis. — The diagnosis from delirium tremens is made by the absence of disorientation and by the marked prevalence of auditory hallucinations in the form of threatening voices. It must not be forgotten that there exist cases that are intermediate in their symptomatology between delirium tremens and acute hallucinosis. From paranoia the distinction is made by the very rapid systematization of the delusional system, as opposed to the slow evolution in that disease. Alcoholic Psetjdoparanoia. — In some cases of chronic alcoholism a paranoid state is developed, in which psychosensory disturbances (hallucinations) may be of secondary importance or not present at all. The characteristic delusion in these cases is that of marital infidelity. While some of these cases develop primarily upon a background of chronic alcoholism, others may fol- low directly upon an attack of hallucinosis or de- lirium tremens. These cases have a long course, a poor prognosis, and may terminate in considerable impairment. Diagnosis. — This delusion of marital infidelity and jealousy may not be accompanied by any noticeable degree of impairment of judgment or mental cti- feeblement, and in these cases it may be extremely difficult to make a differential diagnosis between this form of alcoholic psychosis and true paranoia. Particularly is it difficult to recognize paranoia with subsequent or coincident alcoholic indulgence. Certain other paranoid conditions, especially of the involution period, may present this picture with the characteristic delusions of jealousy. Differentiation is made by excluding alcohol in the anamnesis. Korsakoff's Psychosis. — The mental state of this psychosis accompanies polyneuritis and is usually of alcoholic origin, but may be caused by other poi as those of typhus, tuberculosis, influenza, diabetes, the metallic poisons, etc., and the Korsakoff syn- drome is seen not infrequently in general paresis and in senility. The signs of polyneuritis may be very slight. Symptoms. — The patient is usually a chro alcoholic and may enter the hospital suffering from delirium tremens. The delirium instead of clearing completely, as is usual, merges into Korsakoff's psychosis, which has often been called chronic alcoholic delirium in contradistinction from delirium tremens, which is an acute alcoholic delirium. The mental symptoms are the result of a charac- teristic combination of disorders of attention and memory, together with a serious defect in the sense of time. The result is a peculiar type of amnesia There is a defect in the recording of present evi resulting in an anterograde amnesia. In more severe cases this amnesia may reach back a considerable distance — retrograde amnesia — but the events of early life and long distant occurrences are well remembered. This defect of memory is associated with a com- posed bearing and apparent lucidity on casual 196 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alcoholic and Drug Intoxication questioning. A more careful examination, however, will show not only this memory defect, but probably also that the patient is disoriented as to time and place. The characteristic symptom is associated with the , i ;l and consists of a peculiar falsification of nory. The gaps in memory are filled by all sorts of fabrications which are narrated in great detail and with a perfeel appearance of lucidity — opportune ibulation. A patient who had been confined to his bed for days ith font- and wrist-drop told inc. when asked where he was the day before, about having gone to the races and detailed his conversation with different person-, described the events, told what horses won, and the like. One such patient says to the physician on approach- ing the bed: "I am pretty sleepy. I have just had a over home and I came over here to lie down in." Asked if his wife had been to see him lately had 'idled the day before), said that he saw her two days ago and added: " I was just out there at the front window a few moments ago to see if she was ing." Being questioned as to what he had for dinner yesterday (he was on a milk diet), said he had ie delicious New York plums, the usual vege- and cocoa." Often delirious experiences seem to be related to the neuritic pain. This same patient told once how a big, black, burly, ugly negro grabbed his sore legs lays before and how it made him angry. Another patient tells how two years ago he was chloroformed by unknown parties. He awoke just hey had escaped from the room and saw a machine .in his right foot. (He suffers from pain and weak- ness in this foot and ankle.) This was crushing the tendons of the instep. He immediately dropped off leep again. When he awoke the next morning the instrument of torture had been removed, but he suffered from pain and weakness in that right foot and also to some extent in the left foot. In many cases the fabrications can be suggested by leading questions and the patient may be led to make almost any statements, no matter how contradictory gestion confabulation. One patient, confined to bed, -when asked what he did the day before, replied: "I took the horse and buggy out and took a drive, my father being in Baltimore; I don't know whereabouts I had him fed; I went down Pennsylvania Ave. and Fourteenth Street." Another patient, when asked what she had for breakfast, proceeded to give a bill of fare, none of the articles of which she really had had. These pseudo-remin iscences are usually unstable and fleeting, or at least seldom told twice alike. Such for instance is the following: " A few weeks ago I was out walking on the Washington Heights, you know, just beyond the Treasury, with a friend. It was during lunch hour at the office. We saw some cattle grazing on the hillside and we thought we would have a little shooting match. I went down to the man and he gave me a gun and I fired away and hit a steer right behind the ear. It, of course, killed him. They all laughed and considered me a crack shot. They sent me a check for it the next day. It was for a pretty large amount, but I do not remember just how much. I suppose by looking up the records I could find just uuch they did give me." Sometimes, however, some of them become fixed. It is fairly common, for example, for women to ive and act as though they had a baby in bed with them. With this state of mind the patient is usually very poorly oriented if not completely disoriented. His time sense i< particularly affected. Physically the patient typically has all the signs of a polyneuritis, which of course differs in its distribution according to the etiological factor. In the alcoholic type, which is the mo t common, wrist-drop and foot-drop are characteristic symptoms. Of com e various unusual and anomalous involvements may occur, for example, of the cranial nerves. Bulbar and vagUS involvement are naturally most serious. Inasmuch as the pathology of the disease shows that it is not confined to the peripheral nerves but is general, involving the whole of the nervous system, cord, basal ganglia, and cortex, and inasmuch also as there seems to be some tendency to the localization of the pathological process, we might expect to find, and as a matter of fact do find in certain cases, focal symptoms. These an- the various types of aphasia, apraxia, reading and writing disturbances, homonym- ous hemianopsia, etc. Pupillary disturbances are not infrequent. In- equality of the pupils, sluggishness to lighl and accommodation reflexes, and transitory Argyll- Robertson pupil may be present. .More rarely various kinds of ocular palsies or muscular weaknesses occur. Clinical Forms. — Various clinical types of the disease have been described according to the promi- nence of special symptoms. Thus Dupre describes five as follows: (1) amnesic, (2) confusional, (3) delusional, (4) anxious, and (5) demented. Knapp describes eleven forms: (1) delirious, (2) stuporous, (3) demented, (4) hallucinatory without systematiza- tion of false ideas, (5) hallucinatory with systematiza- tion of false ideas, (6) paranoic!, (7) anxious, (8) expansive, (9) manic and melancholic, (10) poly- neuritic motility psychosis (of Wernicke), and (11) anomalous. Of course it will be understood that this separation of forms of the disease is nothing more than giving the name of the most prominent symptom. Thus in the stuporous type stupor is especially in evidence, etc. Diagnosis. — The association of the peculiar falsi- fication of memory, with confabulation and usually disorientation, with foot- and wrist-drop is charac- teristic. Paresis is to be distinguished by the absence of evidences of polyneuritis. Dream States. — Less common and more unusual effects of alcohol are the conditions of so-called trance, automatism, double consciousness, spontaneous som- nambulism, which are followed by amnesia. In these conditions the subject of alcoholism may do almost anything imaginable, make contracts, transfer prop- erty, commit criminal acts, take long journeys, enter into complicated business or professional transac- tions, and later have absolutely no knowledge of what he has done. During a protracted debauch the sub- ject may suddenly start off on a journey and travel under an assumed name, meanwhile conducting him- self in such a manner as not to lead to any comment on the part of those whom he meets. Suddenly, without warning or after a night's sleep, he "wakes up'' to a realization of his true situation with abso- lutely no memory of how he got where he is or what he has been doing since he started away from home. As the name indicates, this condition has been de- scribed as one of automatism, but a moment's con- sideration will serve to show that acts of such a com- plex character cannot be automatic acts. The fact that no recollection remains of what was done has been used to argue unconsciousness, but that is equally inconceivable. Hundreds of miles could not be travelled by an unconscious man without attract- ing attention. The mere fact that the patient has forgotten what occurred is no reason why he must necessarily have been unconscious. I have been fully able to demonstrate that consciousness actually did exist in certain cases that I have studied which were followed by amnesia, and as a result I am con- vinced that the same condition might be found to exist in others. Some persons are especially liable to this form of mental disturbance, and it may re- peat itself on the occasion of renewed intoxication. 197 Alcoholic and Driitf Intoxication REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Its psychopathological basis is probably a dissocia- tion of consciousness. Course. — Chronic alcoholism, whether interrupted or not by any of the forms of mental disturbance de- scribed in this chapter, tends to an ever-increasing dementia, alcoholic dementia. Mental enfeeblement is a symptom from the outset and is noticeable at first in the esthetic and moral sphere. The previously proud, well-dressed man becomes slovenly in his habits and unkempt in his appearance. Incapable of the close and continuous mental application of former years it becomes impossible for him to meet the requirements of his business or professional life and lying is resorted to in finding excuses. This is followed by moral obliquities of a more serious nature in which the sexual element is apt to predominate and result in medicolegal complications. Memory is early and noticeably affected. The every-day affairs of life are forgotten, so that the subject of alco- holism neglects to keep appointments, forgets impor- tant business engagements, etc. Judgment and the reasoning faculties are similarly enfeebled, until finally the most profound degree of dementia is reached, hastened perhaps by apoplectic insults which are not uncommon. Pathology. — The gross pathology of alcoholism has already been indicated. Cirrhotic liver, chronic ne- phritis, fatty heart, chronic gastritis, arteriocapil- lary fibrosis, cerebral arteriosclerosis, and cerebral hemorrhage. The principal lesions found in the brain are pachy- meningitis, edema, congestion, thickening and opacity of the piarachnoid, atrophy of the convolutions, sclerosis of the vessels, degeneration of the cells, and increase of neuroglia. Treatment. — The treatment of delirium tremens and the other acute alcoholic psychoses should be sup- porting; liquid concentrated food, predigested if necessary. The bowels should be kept free and the kidneys kept flushed by a goodly supply of fluid. Heart stimulants are often necessary, digitalis, caffeine, strychnine, to combat cardiac failure, and hypnotics to induce sleep and give rest. The latter should be carefully selected with reference to the pa- tient's condition, depressing agents, such as chlo- ral, giving place to safer ones as trional if there is much heart embarrassment. The after-treatment con- sists of abstinence from alcohol, tonics, nourishing food, and regulation of the emunctories. For the excitement especially hydrotherapy in the form of the continuous bath is valuable. The thing to be kept constantly in mind in these eases is the matter of nourishment. If the patient does not take sufficient food, tube feeding should be begun at once without any delay in temporizing. Food alone will often ameliorate in a remarkable manner the excite- ment and the insomnia. The medicinal treatment of chronic alcoholism should be tonic and supporting. Strychnine for a general nervous and cardiac stimulant, ergot if there be symptoms of "wet brain," capsicum and bitter tonics for the gastric condition and anorexia; atten- tion to the emunctories, moderate exercise, baths, massage and electricity for their general tonic effects; sedatives and hypnotics with caution; a modified "rest treatment" if there is marked neurasthenia, and later a sufficient amount of mental and bodily exercise to keep the patient healthfully occupied. The matter of isolation is an important one. I feel convinced that in all cases in which the habit is firmly fixed isolation is highly desirable, if not im- perative, as in these cases the patient is unable to resist temptation and, as soon as opportunity presents itself, will lapse. After confinement for a few months, during which the patient is restored as far as possible to physical health, he is in condition to abstain if he wants to and is able; if he does not wish to or if he suffers from too great weakness of will, he will return to his old practices and his case is hopeless. If he does wish to stop drinking, however, he has been given the best possible opportunity, an opportunity which should be early extended in all cases and not offered when by long-continued indulgence the case is of necessity hopeless. Opiumism. — Causes. — As in other varieties of nar- comania the most important cause is the neuropathic diathesis. In this class of patients the habit is often initiated by the use of morphine to relieve the periodic pains of neuralgia, tabes, dysmenorrhea, rheumatism etc., or the mental depression incident to worry, loss of position, grief, and the like. A great many ca are unfortunately traced to the carelessness of p) cians in prescribing the drug, and as if in retribution medical men furnish the largest quota of sufferers (fif- teen per cent.). Symptoms and Diagnosis. — The symptoms of a sin- gle dose are at first those of mild stimulation of the mental faculties, followed by a period of quiet, half- waking, half-sleeping, interrupted by multiform pleas- ant hallucinations (predominantly visual) which show no tendency to delusive elaboration in the waking slate. This condition is followed by malaise, head- ache, dry mouth, constipation, and nausea. The physical symptoms of prolonged use of opium in any of its forms are anorexia, irregular action of bowels, constipation alternating with diarrhea, car- diac weakness, general muscular weakness and tremor, miosis and sluggish pupils, impotence, amenori diminished sensibility, paresthesias, sensation of coldness. Mentally there is a gradual degradation. The memory and power of attention become impaired and the capacity for initiation is lost. Then marked impairment in the ethical feelings and pre- viously honest persons will begin by lying out "f business engagements and about the taking of the drug and end by associating with the most degraded persons and resorting to any means whatever, even criminal, to obtain the drug. Some persons who have taken opium in some form for a considerable time and in large doses develop an hallucinated state that may be of paranoid coloring or may be distinctly delirioid. Thus one patient (laud- anum and whiskey) on admission to the hospital said that her food was poisoned. Another patient (mor- phine) is restless and excited, has hallucinations of hearing, and carries on conversation with imaginary persons. Sometimes her language is violent and abusive, she threatens her imaginary persecu and will jump out of bed and run through the hall-way looking for the people she thinks are after her. The diagnosis can often not be made without the anamnestic data. The patients frequently deny their habit — mendacity is a prominent symptom, and they are often cute enough to find means of indulgence even though carefully watched. The moral deg- radation is pronounced and they will go any length to obtain their drug. Symptoms which should ex- cite suspicion are periods of torpor and languor in marked contrast to the activity of alcoholism, amount- ing at times to an inability even to sit up, occasio signs of stimulation, small pin-point pupils, yellowish- brown cachectic complexion, and, above all, the numer- ous scars of hypodermic injections. In conditions in which a diagnosis is necessary it is to be remembered that morphine can be recovered from the urine and stomach. The least serious method of taking the drug is by smoking, the next more serious by mouth, and the most serious method is the hypodermic. Morphine is distinctly more dangerous, more dominating after habituation, than the other forms. It is, too, more serious in its effects upon the general health. Prognosis. — The prognosis is not good and except in such cases as are not complicated by neurotic or I '.IS REFEREXCK HANDBOOK < >F THE MEDICAL SCIEN( I 3 Alcoholic anil Drue Intox Icatlon psychopathic taint or disorders relieved by opium, recovery is hardly to be expected. >logy. Opium has less tendency to produce [issue degeneration than alcohol and many persons continue for years to take small doses With no ap- parent harm. Trent i',: "i. The treatment of morphinism has to do with the removal of the drug and the symptoms of abstinence. Isolation is more necessary than in alcoholism, as these patients make more effort to tin their accustomed stimulant surreptitiously. It II, in accordance with Dercum's suggestion, not to n stopping the drug until thepatienthasbeenunder itment fur a time, confidence being established, and t he general health raised to the best standard. The luxe can then be rapidly withdrawn, in ac- vrith the method of Erlenmeyer, leaving patient on about 0.15 to 0.20 gram morphine per i, below which amount serious symptoms are apt present themselves. From this point on tfie withdrawal should be gradual. Symptoms of ab- if they appear, are referable to the heart, aach, bowels, and nervous system: the}' are circu- latory failure, respiratory disturbance, pyrosis, vomiting, diarrhea, tremor, general debility, and hallucinatory delirium and sometimes profound ipse. Ball has called attention to pollutions and erotomania which may result from abstinence. For the cardiac weakness digitalis or sparteine hypoder- illy should be used; for the pyrosis, bicarbonate of nin; vomiting and diarrhea should be treated in ce with general principles (bismuth, etc opium being avoided. If the mental and physical symptoms become grave morphine should be given and will usually relieve them. The evening dose should be omitted last, to combat any tendency to in- somnia, and full feeding, massage, and hydrotherapj' aluable adjuncts. Meconarceine (Duquesnel's solution) has been used Jennings a- a substitute for morphine for a few days after entire discontinuance. It is necessary to ■ ■all attention to the danger of cocaine for this purp< ise. ine has also sunk into disuse and the synthetized derivatives of morphine, heroin, dionin, and peronin, aot be said to be any better. Their use is founded on a wrong theory and is fraught witli danger. Cases i ious addiction to codeine and heroin have been reported. unism. — Causes. — Addiction to this drug has in a great many cases come about by attempting to substitute it for morphine, and as a result pure cases of cocainism were formerly more rare than at present, line has been used so much of late in dentistry, minor surgery, and especially nose and throat work, that a knowledge of it has become more or less general. The victims are often those who have commenced its use for its analgesic effects and are frequently < ians. ptoms. — The symptoms resulting from the use of cocaine are those of marked stimulation. The pulse is increased, pupils are dilated. The patients are active and extremely talkative, often repeating re- marks a number of times; they are constantly busy. ~ome of them writing endless letters, and their whole tearance indicates an acute intoxication. The ef- - are, however, very fleeting and the dose has to be frequently renewed. Chronic addictions result in marked emaciation, cachectic anemia, insomnia, times epileptiform attacks and various paresthe- tic most marked of which is a sensation of crawl- inder the skin ("cocaine bug")- In the psychic re occur incapacity for mental application, aed moral sense, mendacity, irritability, im- paired judgment, and sometimes the delusion of marital infidelity. These symptoms may be followed by mental confusion with hallucinations, or by a paranoid state. From true paranoia this is differen- ■'1 by the greater variety of delusions, those of paranoia being less Variable, rather noticeable for their QOtony. In the paranoid -tale of alcohol- ism, on tin- o'tner hand, the hallucinations are more stereotyped. The absl inence symptoms are ncit so severe as with morphine and may not appear for several days. Erlenmeyer has called attention to a profoundly depressed, lacrymose, demoralized condition, with moaning and sighing, which may supervene. The persecutory delirium may persist for a long time and constitute the patient a dangerous individual. Morphine and cocaine addictions may also bring out a neuropsychopathic state, with symptoms of psychasthenia — morbid impulses, insistent ideas, etc. line such r:i-i sutleied fn.ni a convulsive tic with mental depression and suicidal impulse. Recovery followed prolonged abstinence. Treatment. — Isolation should be insisted upon. The drug may be withdrawn rapidly a- the symptoms of abstinence are not as marked as in morphine. The prognosis of deprivation is good, but relapses are pretty a] it to occur. Miscellaneous Intoxicants. — V a r i o us other drugs may produce marked mental disturbances as a result of acute or chronic poisoning or habituation. Ihe limits of this article permit only of their mention. They are chloral, cannabis indica, somnal, sulfonal, paraldehyde, ether, chloroform, aspirin, antipyrine, phenacetin, trional, chloralamid, iodoform, belladonna, hyoscyamus, salicylic acid, quinine, the preparations of lead, arsenic, and mercury, and the bromides. It should be realized that many of these drugs are drugs in common use and that unless the possibilities of their producing a psychosis are borne in mind such an accident may arise as the result of large doses or even of moderate doses in especially susceptible persons. It is just such cases as these together with the ■ ases that arise as the result of taking several drugs, analgesics and hypnotics, that one meets and finds that no suspicion has arisen as to the true cause of the trouble. Attention has recently been called to the frequency of bromide delirium (O'Malley and Franz, I asamajor). Casamajor has called particular at- tention to the frequency with which bromide de- lirium is produced in the treatment of alcoholism. The character of the delirium in these cases may 1 it- described as dream-like. The content of the delirious experiences reminds one of delirium tremens, while the tendency to confabulation reminds one of Korsakoff's ps3'chosis. The patients are not usually apprehen- sive and restless as in delirium tremens, but more composed and may be dull and stupid, though there are not infrequently outbreaks of violence dependent upon paranoid experiences. The following extracts from cases will illustrate these points: The patient, a woman, fft. thirty-six, had been tak- ing morphine hypodcrmically and bromides, chloral, anil hyoscine hydrobromate. On admission she sees men in rubber garb who stay in the water and look at her constantly. She also sees the king and queen, bugs and snakes, and bull-dogs with huge open mouths. Says the king and queen congratulated her when she picked up the broken glass at F — 's on Ninth Street. She hears bull-dogs scream and answers imaginary voices. Electricity is played on her by Dr. B — and she feels snakes which crawl about her neck. Says there are men who throw green pow- der about the room. Another patient, woman, a?t. thirty-eight, had been taking antirheumatic treatment with aspirin to relieve pain and later morphine and hyoscin. She related the following delirious experience that oc- curred just before admission: " I believed that a party of us were going down in the country on a picnic and that a cavalry regiment had been ordered out. When we got started, we found that a whole regiment of Indians and negroes were following us. We went to the place in the coun- 109 Alcoholic and Drug Intoxication REFERENCE HANDBOOK OF THE MEDICAL SCIENCES try where I was born and brought up, and there we found a hospital which was to be used for earing for us until the negroes and Indians were allowed to kill us. The patients in the hospital were all in little beds just like at Providence, but were all sitting up. The doors were looked so that we could not get out, but I could hear the negroes and Indians talking about killing us. They decided to divide the party up and take us to their different camps. They also talked of blowing the hospital up with dynamite. They talked of setting fire to a haystack that was situated near my mother's home. I heard them pre- paring fuse which was to be used in exploding the dynamite. I was dreadfully afraid all the time I was at Providence Hospital and felt that I was among enemies. I thought the nurses were trying to do the best they could for me, but that they were in the employ of the Indians and negroes." Another patient, female, let. thirty-seven, took "bromo-quinine" for two weeks when she developed a delirium. The following is the substance of a letter she wrote while suffering from the delirioid experiences. "Just go there, I cannot talk, I am under a terrible spell, I do not know what it is, but it is the most wonderful experience I ever had. I am hypo, I am hypnotized. I ma}' be in a trance for three months. Do not for God's sake, bury me alive — Molly. Keep me out of the grave four or five months. It will be all right. You will hear some things that will surprise you. Ben, go in that room for God's sake, there is a man in there, he scares everybody dumb, I cannot talk, but for God's sake, break down that door. Take Jack, he has got a good strong arm, break that door down. That poor man is suffering, I saw him do something terrible, and it awed me so I am half paralyzed. For God's sake, break that door down, hurry up." In a case of bromide delirium (reported by O'Malley and Franz) the patient had taken on an average 300 grains of bromide daily for fifteen days. Her case illustrates well the dream-like character of the hallucinatory and delusional experiences. She was disoriented on admission. Three days later said she had spent the night in the city, was with a large crowd of men and women, that her husband was dead and that she had seen his body buried. The next day, asked where she had been the night before, said, "I was over to the gipsy camp; I went over in northeast Washington and saw them kill my husband — smash his head; his brother, who is a sculptor, made a form of his head; I saw it; he will be buried to-morrow." A few minutes later her husband visited her. She told him she thought he was dead, took him to task severely for putting her in the hospital and being unkind to her, but throughout the visit insisted that he had been killed. Six days after admission she still had visual hallucinations — saw cats and rabbits; thought some of the women patients were men, thought she had to walk on cats' heads when she left her bed and that the physicians were watching her from the register plate in her room. Later she complained that she was "spirited away every night by some influence." In the treatment of these cases the principal thing is, of course, the removal of the drug, though often the underlying condition, for which the drug was taken — pain, insomnia, must then be treated. It must lie borne in mind that it may take several weeks for the patient to clear up after all drugs are discontinued. William A. White. Aldehyde. — The aldehydes form a class of chem- ical compounds. Of this class, acetic aldehyde is the commonest example, and accordingly the" word aldehyde, when used singly, is understood always to mean that substance. ' Acetic aldehyde, CTL.- COH, is, from the point of view of chemical com- position, the first outcome of the oxidation of com- mon — ethylic — alcohol. It resembles alcohol very closely in physical and physiological properties, being a thin, colorless fluid of pungent smell and taste; inflammable, miscible in all proportions with water, alcohol, and ether; antiseptic, irritant, and narcotic. It is not used in medicine. R. J. E. Scott. Alder. — Abuts; Brook or Tag alder. Alnus Tournef. is a genus of a dozen or more species in the family Betulaccw, distributed through the north temperate zone, and extending along the mountains into the tropics. The bark and leaves are rich in tannin, and therefore strong astringents, without special char- acter. They are used in tanning, and have numerous domestic medicinal uses, all depending upon the action of the tannin. Finely powdered, they have been found very useful by travellers for applying to chafed surfaces. The wood, deprived of the bark, makes a favorite charcoal for powder manufacture. H. H. Rusby. Alder, Black. — Prinos; Wititerberry. The bark of Ilex verticillata Gray (fam. Aquifoliacece). (For the properties of other species of this large and interesting genus, the reader should consult Mate, Holly, and Cassine.) The plant under consideration is a lars;r. shrub, growing in hedges and borders of forests in the Northeastern United States, and displaying in fall and early winter slender branches densely covered with shining, scarlet berries. The bark is smooth, grayish or whitish ash-colored, and when dried for medicinal use is in " thin, slender fragments, about one millimeter (■,'- inch) thick, fragile, the outer surface brownish ash-colored, with whitish patches, and blackish dots and lines, the corky layer easily separating from the green tissue; inner surface pale greenish or yellowish; fracture short, tangentially striate; nearly inodorous, bitter, slightly astringent." It contains tannin, resin, and an amaroid. No special physiological properties are known, but it has been used as a tonic and mild astringent. The dose is two to four grams (5 ss. to i.). H. H. Rusbt. Alectrobius. — A genus of ticks which contains some species that are parasitic on man. See Arachnida. Aleppo Evil. — See Oriental Sore. Aletris. — I'nieorn root; Star grass; Mealy starwort; Colic root. Sometimes erroneously called Blazing- star. The rhizome of Aletris farinosa L. (fain. Liliaceai). This plant is a low, slender, erect, per- ennial herb, common in swamps and low land- cast of the Mississippi River. It has been much used in domestic practice as an abdominal stimulant. It contains an unknown bitter principle, soluble in alcohol and somewhat in water. The use of !li» drug is purely empirical — in colic and rheumatism. The fluid extract is the best form of administration, and is given in doses of 0.5 to 1 c.c. (ni viij.-xv.). Seven other species of Aletris are known, one in tin' Southern States and six in Fastern Asia, but their properties have not been investigated. H. H. Rt/sby. Aleurobius. — A genus of the cheese mites. Tiirn- glyphince, which is found in flour, fruit, tobacco, cl se, and other organic materials. A. farina has been observed to be the cause of a cutaneous eruption on men unloading wheat. See Arachnida. A. S. !'■ 200 REFERENCE HANDBOOK OF THE .MEDICAL SCIENCES AlKlers Alexander of Tralles. — Alexander was born in fralles, a small city (if Lydia, during the reign of the ■mperor Justinian, about the middle of the sixth entury. After travelling for some time in Italy. Spain, and Egypt, he finally settled in Rome, in \ hich city he published several treatises I hat summed m i lie results of his long experience in the observation mil treatment of disease. Here are the titles of iome of these works, several editions of which (both •k and Latin) were printed during the period ,, 1498 to 1772: "Libellus de febribus," "De arte lica," "De corporis partium segritudinibus," " De mbricis," and "Problematum medicorum et nat- tralium libri duo." These books display an extra- ordinary degree of independent thinking on the pari if the author, for it must be remembered that he 1 at a time when the science of medicine had sunk lo a very low level; indeed, they are worthy in many ects of being read by physicians of the present time. A. H. B. Alexin. — This is the term originally used by Buchner to designate that substance in immune scrum which caused bacteriolysis. It was later overed that this substance really consisted of two bodies, one specific, the amboceptor, the other -essiug little or no specificity now called the complement or alexin. The alexin, also called end- body or cytase, probably consists largely of a pro- ftic ferment which acts upon cells causing 1yds. It is present in all sera to a greater or lesser extent and is unable to attack cells unless joined to them by means of the amboceptor. Alexin is destroyed by heating to 56° C. for half an hour and gradually becomes inert on standing even though in the cold. \ scrum thus "inactivated," that is robbed of its alexin, may be reactivated by the addition of fresh scrum from the same or some other animal. As alexin from one animal can be used to activate the scrum of another or to cause lysis of a number of different cells it evidently has but little specificity. [he complement does differ to a certain extent for different cells but this difference is slight and may usually be disregarded. The phagocytes are believed chiefly to be concerned in its production but it is probable that there are other sources for it. For a .1 tailed discussion of this subject and the place which the alexin holds in immunity reactions see the article on Immu nity. Ralph G. Stillman. Algiers.— Algiers (latitude 36°, 37' N.; longitude 3°, 2' E.) is the capital and seaport of the French Colony of Algeria. It is almost directly south from Marseilles, upon the Mediterranean coast of Africa, and has a population of 154,000, composed of a variety of races. The town has a most attractive situation on the slope of a hill facing the east, and as seen from the sea, it is exceedingly picturesque and striking, its white houses rising in a succession of terraces from the water's edge to the hills in the rear. The luxuriant vegetation also adds to the beauty of the scene. The city consists of the modern French town near the seashore, composed of public buildings, residences, ■i handsome boulevard, and a well-built quay; and the old city of the Turkish period on the slope of the hill back of the French quarter, culminating in the Kasba, or former palace of the deys, about 500 feet above the level of the sea. This old city is compose. 1 of a crowded "mass of low, flat-roofed, whitewashed houses intersected by the narrow, crooked, dark, and dirty streets characteristic of an Oriental town." < * 1 1 the slope of the hills above the lower town, facing the east, is the picturesque suburb of Mustapha Superieur, about two miles from the center of the city. This is the resort of choice for invalids and others who spend the winter in Algiers. Here are excellent hotels and villas with fine gardens, and the summer palace of the Governor General. Many English and Americans reside here; there are :m English club, English physicians, English churches, golf links, and all the attractions and luxuries of a first-class winter health resort. It is well supplied with water, and the sanitary condition is good. The hills about are covered with vegetation and flowers, and there are very attractive walks and drives. The winter climate of Algiers is characterized by mildness, moderate humidity, and an abundance of sunshine. With the exception of the humidity, it resembles that of Egypt and the Riviera. In summer it is hot and dry. In many respects it resembles the climate of those portions of Southern California near the coast. The mean annual rainfall is about thirty-six inches, the most of which falls in the winter. The rain comes in heavy downpours and suddenly ceases. It is quickly absorbed by the sandy soil. The following tables, given by Dr. Bennet, indi- cate the distribution of the rainfall and the number of rainy days. Mean Rainfall at Algiers. 1839-1845. 5 inches. May 1 J inches. November December S inches. January 6 inches. February 5 inches. March 3 inches. A] iri] 4 inches. June . . . $ inch. July inch. August i inch. September 1 inch October 21 inches. Number of Days and Nights in t 1S43 on Which Rain Fell. Days. Nights. November 10 December 5 January 10 February 9 March 9 April 1 Total 44 10 34 Days May 3 June 2 July August September 2 October 3 Total 10 Nichts 1 1 The relative humidity is fairly high, as shown by the following table from Hann: Nov. Dec. Jan. Feb. Mar. Winter Mean, Dec. -Feb. 68 % 73 % Jan. 73% Feb. 72% Mar. 69% Winter Mean, 73^ The average number of fair days in the course of the year is 233. The mean winter temperature from December to February is 54.38° F., and the mean annual temperature is 67.22° F. The duration of the season for invalids, according to Weber, is from November to the end of April, and for this period the average temperature is 50.99° F. There are not infrequent sudden falls of tempera- ture during the days, such changes occurring most commonly between four and five in the afternoon. The daily variations of temperature, according to Weber, are from 10.8° F. to 14.4° F.; while the differ- ence between the day and the night temperature is given by Rochard as from 5.4° to 9° F. The prevailing wind for the year is the northwest from the Mediterranean, which often blows with great violence. The west wind brings rain, and is the one which is most frequent in the winter season. The Sirocco, which blows from the desert, is a dry, dusty, hot wind, and is most prevalent in the summer, although it occurs also during the winter season. It i~ always oppressive and exceedingly disagreeable on account of the clouds of dust which it brings with it from the Great Desert. Dust is one of the very annoy- ing features of the climate of Algiers. The wind is not regular, and, although its prevalent direction is from the northwest, it also comes from the north and east during the winter months, and the sudden alterations of temperature mentioned above are said by Huggard (Handbook of Climatic Treatment, London, 1906) to be due to this irregularity. The north and northeast winds blow most frequently during the spring and summer months. The rate of mortality is said by Huggard to be 201 Algiers REFERENCE HANDBOOK OF THE MEDICAL SCIENCES high, probably due to the unhygienic mode of life of the native inhabitants. Such a resort as Algiers is favorable for those per- sons who thrive best in a warm, sunny winter climate where the}- can spend a greater part of the day com- fortably out of doors with attractive surroundings, such as the aged and delicate and those convali - from acute diseases. Cases of emphysema and chronic bronchitis are said to derive benefit from this cli- mate, although opinions differ with regard to this. For instance, Huggard (loc. cit.) says that Algiers " is hardly the place of resort for those who catch cold easily. Such persons," he says, "are very apt to be troubled with rheumatic affections or with recurrent bronchial troubles," and one would readily think this might be true when he remembers the sudden changes of temperature and the dust. For tuberculosis, for which this resort formerly had a reputation, one would now hardly recommend it. A moderately moist, warm marine climate, with frequent high winds and dust and sudden variations of temperature, is far from the best one for this disease, although certain cases may do well there when for any reason the high altitudes are not applicable or the dry inland resorts are badly borne. However, Dr. Charles Theodore Williams (Aero-Therapeutics, 1894) speaks thus favorably from his own personal experience: " Of the dozen consumptive patients of whom I have notes who have wintered once or oftener at Algiers the large majority improved greatly and num- ber at least two cases of arrest; but I note that the greatest improvement took place where patients re- sided in villas with gardens and not in hotels. In one case where a young lady, a member of a very consumptive family, developed the disease and a very considerable cavity had formed in one lung, complete contraction of the cavity took place with arrest of the disease in two winters, and the lady has since married and has resided for the last nineteen years in England without any signs or symptoms of relapse. Another lady, with well marked tuberculosis of one lung, spent two winters in a villa at Mustapha Su- perieur with the result that the disease became ar- rested, and since that date she has been able to pass twelve winters in Scotland with impunity." Two arrested cases out of twelve, or sixteen per cent., would be considered a very poor result in the light of present experience, and from this showing. Algiers could not be recommended as a favorable resort for the successful treatment of tuberculosis. Edward 0. Otis. Alhambra Springs. — Jefferson County, Montana. Post-office. — Alhambra. Access. — Via Northern Pacific or Great Northern Railroad. The hotel is within 600 feet of the Great Northern Depot, and is equipped with every modern convenience. These springs are located seventeen miles from Helena, at a level of 4,200 feet above the sea, the sur- rounding country being broken and mountainous. A dry and salubrious climate, with varied and pictur- esque scenery, characterizes this region. The hills and mountains are covered by different varieties of pine, fir, and cypress, while the bottoms are dotted with groves of alder, willow, mountain ash, poplar, and other trees. Many varieties of plants have been found in the neighborhood, which, it is said, have never yet been classified. The ideal location has earned for Alhambra its title of "The Garden Spot of Montana." In the Government Forest Reserve four miles back of the hotel, game is still abundant, consisting of grouse, pheasant, deer, elk. mountain sheep, and numerous other varieties. The springs are situated in an angle formed by the junction of two creeks, in which mountain trout abound. They are twenty-two in number, and vary in temperature from 90° to 129° F. The water has 1 n analyzed 202 by the chemist, Emil Starz, Ph. G., Helena, Montana who has given the following report : Solids.. Parts per Gallon-. Calcium bicarbonate 10.06 Magnesium bicarbonate 4 40 Potassium carbonate 4.16 Potassium chloride 6 .00 Calcium sulphate 1 .75 Alumina 272 Sodium sulphate 24 76 Silica 6 46 Toul 60.31 "The Thermal Springs, located at Alhambra, Mon- tana, possess great medicinal virtues and rank among the best medicinal thermal waters in the United States. They are eminently effective in all cases of rheumat- ism, especially in chronic rheumatism, renal calculus, kidney, liver, and bladder diseases. Their curative properties are due not only to the temperature of the water, 129° F., but also to the mineral constituents contained in it. The drinking of this water is in- dicated and most beneficial in all kinds of stomach troubles, especially when such are due to a hyper- acidity of the stomach. At least one or two quarts should be drunk during the day and one or two baths a day used." Abundant facilities for hot and cold bathing, with a plunge and swimming bath, vapor and mud baths, are provided. Hospital accommodations are fur- nished for invalids. Emma E. Walker. Alicante. — This Spanish city of 30,000 inhabitants lies upon the shore of the bay bearing the same name, on the eastern or Mediterranean coast of Spain, and about fortv miles south of the middle point of that coast (lat. 38° 20' N.. long. 0° 30' W.). Extending in the form of a crescent along the northern shore or head of the bay, and dominated by a rocky hill, some 400 feet high, the town is tolerably well sheltered from the north and northwest winds, the bay being open only to the westerly winds. " The landward environs are dreary," says Baedeker; "but the distant mountains, the castle, the harbor, and the sea combine to form a memorable picture.'' 'The view from the east mole of the harbor," con- tinues the same authority. " with its white, flat-roofed houses, its palms, and the bare and tawny cliffs of the castle hill, has probably no parallel in Europe." The climate is a mild and dry one, drier than the Riviera, the annual rainfall being only 16.93 inches, of which (according to Lorenz and Rothe, quoted by Dr. Weber, in Ziemssen's " Handbook of General Therapeutics") 20.7 per cent., or the extremely small quantity of 3.5 inches, falls during the winter months. The percentage of clouds prevailing in the sky of that portion of Spain in which Alicante is situ- ated is much lower than is found in any other part of Europe, Italy and Greece included. The relative humidity of Alicante the writer has not been able to ascertain; but at Valencia, some eighty-five miles north of Alicante, the mean yearly relative humidity is 66 per cent., and it is probably somewhat les- at Alicante. The mean annual temperature is 64.4° F.; that of winter being 53.5° F. Another authority B the mean winter temperature as 60° F. There is no mistral or dust. The present condition of the water supply is not known to the writer; it is probably the same as when Dr. Bennet wrote of it in 1S75, which consisted then of a large spring and rain water tank. The accom- modations are said by Dr. Weber to be good. The wine of Alicante is famous, and. besides a large com- merce, the town possesses an extensive tobacco fac- tors', which employs 400 Spanish girls. When a mild, dry, and sunny climate is con desirable for various conditions of debility, anemia, convalescence from acute diseases, and the like, Ali- REFERENCE HANDBOOK OF TDK MEDICAL SCIENCES Mini, lit ante would seem admirably to fulfil these conditions ases of latent scrofula, asthma, bronchorrhea, albu- ninuria, and rheumatism are also said to do well here. Edwaud O. Otis. Aliment. — Food or aliment is matter which, in con- unction with the air, supplies the elements necessary ( ir the maintenance, growth, and development of the irganism, and is thus the source of the power on which vitality of the organism is dependent — i.e. the -mine of the heat, mechanical work, and other forms if energy liberated in the body. Hence, in the tdest sense, true aliment is a mixture of food- - and water, together with the air, from which - the uxyni'ii necessary for the oxidation of the ormer and by which energy is liberated. Again, siologically considered, true aliment, especially in the animal kingdom, is to be distinguished fromso- d "food" as being only that portion of the food which is either directly available for absorption, or convertible by the digestive juices of the body into ible and more or less diffusible products, appro- ite for absorption by the blood and lymph. The food of vegetable organisms is quite different from that of animal organisms. Moreover, the nature of the processes involved is likewise quite different, vegetable organism, by a synthetical process — a building up of more complex bodies from simpler ones — derives its nourishment from the inorganic world; ells appropriate such of the inorganic principle- as are needed for its growth, and convert them under the influence of the sun's rays into organic compounds which enter into its own structure. The animal organism, on the other hand, does not possess this power to a great extent and thus we look to the creative power of the vegetable kingdom as the source, either directly or indirectly, of the aliment of animals. Moreover, the vegetable matter which thus serves as food not only furnishes the material necessary for the growth and life of the organism, but it contains, in addition, stored up within its molecules, a certain amount of latent force derived from the solar energy originally used in its construction. Animal organisms, by a process of transformation quite the reverse of synthetical, convert the pre- formed animal or vegetable organic matter into allied or simpler forms, which are absorbed into their own tissues. Animal food possesses stimulating proper- tics, due, without doubt, to the crystalline nitrogenous bodies contained in it. Organic matter once entered as a part of an animal organism and applied to the purposes of life is decomposed or broken apart, and its decomposition products are ultimately reconverted into inorganic principles. There is thus a comple- mental relationship between vegetable and animal life and the inorganic world. The plant, by a se- lective action, appropriates as an element of nutrition certain kinds of mineral matter, together with nitrogen in the form of ammonia and nitrates, from the soil in which it grows, at the same time drawing from the air carbon in the shape of carbonic acid, while hydrogen and oxygen are supplied to an unlimited extent in the form of water. The vegetable products thus formed serve in turn as the food of animals, while the latter at every breath pour forth carbonic acid and water, which utimately find their way again, more or less modified, into the tissues of plants. These, together with the nitrogenous excreta, products of the meta- bolism of life, and the postmortem decompositions which follow, continually serve in their variously modified forms as agents by which the conservation and transference of energy are accomplished. Now, since food is the source from which the various elements of the body are supplied, it is evident that to fulfil its purposes food must contain all of the elements present in the body. These are, of course' not free, but in a state of organic combination, for it is only in the latter case that they are of service as food. Aside from the elements which appear as inorganic sails, there are in the body at the mo I bul seven elements, three of which are present only in small quantity. These seven elements are en lion, hydro- gen, nitrogen, oxygen, sulphur, phosphorus, and iron. Any substance which as food is to satisfy the re- quirements of life, should contain all of these ele- . in addition to inorganic salts and water. Food as it OCCUI in nature: -d of mixtures of chemically distinct substances which may be eparated into four great divisions, termed food stuffs. Food stuffs are classified as (a) proteins, (6) carbohydrates, (c) fats, and (d) inorganic salts and water. .Many of the comp i included in these groups are to be found in both the animal and vegetable kingdoms, as for example, the fat.- and pro- teins, although minor points of difference in chemical composition and structure may be observed. On the other hand, certain of these substances are present only in the vegetable kingdom, for example, starch, and others such as the gelatin-forming substances are characteristic of the animal kingdom only. Viewed from the standpoint of origin food-stuffs may be classified under two heads, viz., organic and inorganic. In the first division may be placed those compounds which have been produced by the agency of living cells; bodies which contain carbon and are capable of combustion and of furnishing energy. Ihe second group contains substances belonging to the mineral kingdom that have become mixed with the organic materials. Proteins, carbohydrates, and fats are organic compounds. Various salines and water make up the division termed inorganic. Fur- thermore, the organic food-stuffs are divisible into two groups, dependent upon whether the element nitrogen is present in their structure. Fats and carbohydrates are non-nitrogenous whereas proteins contain nitrogen. Following is a partial classification of foods: Organic. Nitrogenous Non-nit rogenous. . T f Water. Inorganic ^ g^ [ Proteins. 1 I Carbohydrates. Proteivs may be defined as complex compounds of high molecular weight made up of carbon, hydrogen, oxygen, nitrogen, sulphur, and sometimes containing phosphorus and iron. The distinctive feature which differentiates protein from the other food stuffs is that nitrogen is present and is contained in the molecule in a form that is available for the physiological needs of the organism. The term protein is derived from -pcurevui (I am the first) and refers to the fact that it forms the chief mass of the organic constituents of animal tissues. The average composition of the best known proteins is, approximately, carbon, fifty- three per cent.; hydrogen, seven per cent.; nitrogen, sixteen per cent.; oxygen, twenty-three per cent.; sulphur, one per cent. Considered from the stand- point of chemical structure our knowledge concerning the proteins is very incomplete although as a result of the recent investigations of Emil Fischer 1 proteins may be regarded as essentially complex anhydrides of amino acids. Glycocoll, or glycine, chemically known as amino-acetic acid, may be taken as an ex- ample of a simple amino acid. The structure of this substance is CH,.NH 2 .COOH. If two molecules of glycocoll are combined in such a manner that one molecule of water is eliminated, a new compound re- sults. Thus: CH,.NH,.CO CH„. NH,. CO OH CH, |H! N.COOH CH 2 .NH.COOH Glycyl-glycine 203 Aliment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Glycyl-glycine is the simplest of an enormous group of anhydrides of amino acids, and these compounds are called "peptids." A combination of more than two amino acids is designated "polypeptid." Through synthetic processes Fischer has succeeded in fastening together various of these amino acids until products have been obtained finally which would respond to some of the chemical reactions most characteristic of the proteins. Previous to this type of investigation our knowledge of the struc- ture of protein was derived mainly from studies of the products resulting from the hydrolytic cleavage of these substances. The products of protein hydrolysis include a long series of amino acids of varying chemical complexity and significance. 2 It is the presence or absence of one or more of these amino acids or the quantitative variation in the content of their antecedents that undoubtedly is t lie reason why some protein substances are not as well adapted to serve the nitrogenous needs of the body as others. The most striking examples illustra- tive of this point are found in gelatin and zein, the latter a protein contained in corn. A clearer con- ception of the varied composition of the proteins may !»■ gained perhaps from the following table 3 in which tin 1 content of amino acids of several proteins is given. Table I Glycocoll Alanine Ammo-valeric acid Leucine a Proline. Phenylalanine Glutamic acid Aspartic acid Serine Tyrosine Tryptophane Lysine Arginine Histidine Cystine Ammonia ( rliadin from wheat flour. 0.9 2.7 0.33 6.0 2.4 2.6 43.0 1.3 0.12 2 4 1.0 3.4 1.7 5.1 Albu- min from egg. 7.1 2 2.3 4.4 8.0 1.5 1 1 l'rrs.-nl 0.2 1.6 Casein from cow's milk. 0.9 1.0 10.5 3.1 3.2 16.0 1 2 0.23 4.5 1.5 5.S -I M 2 59 (I 085 1.9 Zein from corn. 0.5 Present 11.2 1.5 7.0 26.0 1.0 10.1 1.82 0.S1 3.6 Gela tin. 4 II ss 0.56 0.4 2.75 7.62 0.4 These variations in amino acid content are obvi- ously responsible for differences of chemical structure and may account in large measure for the varying physical properties upon which our present classifica- tion is based. Until very recently the classification of proteins was in a state of confusion owing to the fact that several classifications were recognized by various groups of English-speaking scientists. At present in the English-speaking world the British and American classifications only are of value. These are quite similar in a general way, the points of difference being a question of nomenclature and of minor importance. The following is the outline of the American classifica- tion and it will be noted that the term "protein" has been substituted for the older designation " proteid." I. Simple Proteins. (a I Albumins ib) Globulins (c) Glutelins (d) Alcohol-soluble proteins (e) Albuminoids (fl Histories (g) Protamines 204 II. Conjugated Proteins. (a) Nucleoproteins (b) Glycoproteins (c) Phosphoproteins (d) Hemoglobins (e) Lecithoproteins III. Derived Proteins. A. Primary protein derivatives. (a) Proteans (b) Metaproteins (c) Coagulated proteins B. Secondary protein derivatives. (a) Proteoses (b) Peptones (c) Peptids Simple proteins are protein substances which yield only a amino acids or their derivatives on hydrolysis. The albumins are simple proteins that are soluble in pure water and are coagulable by heat. The globu- lins, on the other hand, are insoluble in pure water but are soluble in neutral solutions of salts of strong bases with strong acids, for example, sodium chloride. Albumins and globulins are very often associated, as for example, in blood serum, and in the substance <>f cells. In a general way albumins are more abundant in animal fluids (blood, etc.), while globulins pre- dominate in animal tissues and in plants. Glutelins are simple proteins insoluble in all neutral solvents but readily soluble in very dilute acids and alkalies. Alcohol-soluble proteins are simple proteins soluble in relatively strong alcohol (seventy to eighty per cent.) but are insoluble in water, absolute alcohol, and other neutral solvents. These last two mentioned groups, the glutelins and the alcohol-soluble proteins, occur as constituents of the cereal grains. The best known examples of these two groups are glutinin and gliadin respectively. They make up what is known as the gluten of flour. The elasticity and strength of the gluten and therefore the baking qualities of the flour are influenced by the proportions of glutinin and gliadin, about twice as much gliadin as glutinin being usually considered desirable in bread flour. Albuminoids may be defined as simple proteins which possess essentially the same chemical structure as the other proteins, but are characterized by great in- solubility in all neutral solvents. Examples of this group may be found as the organic basis of bone (ossein), of tendon (collagen and its hydration pro- duct gelatin), of ligament (elastin), and of nails, hair, horns, hoofs, feathers (keratins). The histones arc soluble in water and insoluble in ammonia. They are precipitated by other proteins and yield a coas;u- lum on heating which is readily soluble in very dilute acids. Histones may be regarded as basic proteins which stand between protamines and true proteins. Histones have been isolated from varied sources, as globin from hemoglobin, scombron from spermatozoa of the mackerel, gaduhiston from the codfish and arbacin from the sea-urchin. The protamines are relatively simple polypeptids. They are the simplest natural proteins. On decomposition l lev yield comparatively few amino acids among which the basic ones predominate. Thus far they have been isolated only from fish spermatozoa, and according to origin have been designated salmine, st urine, clupeine, etc. The conjugated proteins are substances which contain the protein molecule united to some other molecule or molecules otherwise than as a salt. Nucleoproteins are compounds of one or more protein molecules with nucleic acid. These substances are the characteristic proteins of the nuclei and hence are found in largest quantity wherever cells are most abundant, for example, in the glandular organs and tissues. By artificial means or during digestion a nucleoprotein is first decomposed into protein and a REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ linn til substance called nuclein; the latter on further decom- position yields more protein ami nucleic arid. 1 Nucleic acid, of which then- may be several types, ,,, ;IV be resolved into a series of peculiar compounds, purine bases (xanthine, hypoxanthine, adenine, ,,„! quanine), the pyrimidine bases (uracil, cytosine, and thymine), a carbohydrate group (pentose), and phosphoric acid. Glycoproteins are compounds < >f protein molecule with a substance <>r substances aining a carbohydrate group other than a nucleic ,i.l The mucus-yielding portions of tissues are particularly rich in the glycoproteins which serve as ibstance to hold together the fibers in tendon ligament, etc. Glucosamine has been isolated , some nf the glycoproteins and is recognized as carbohydrate constituent. Phosphoproteins are compounds of the protein molecule^ with some, as undefined, phosphorus-containing substances i than a nucleic acid or lecithin. Milk, with its and tl gg, with vitellin of the yolk arc conspicuous foods containing phosphoproteins. compounds yield a trace of iron on analysis I although this has been regarded as an impurity it is not at all improbable that it actually exists in the ein in combination. Hemoglobins are corn- els of the protein molecule with hematin or ome similar substance. Hematin is the coloring matter of the blood which acts as oxygen carrier for tissues and is characterized by containing iron in an organic combination. The protein portion of II glob in consists of globin, a histone. Leeitho- firoteins are compounds of the protein molecule with bins. Lecithins are complex substances charac- terized by containing nitrogen and phosphorus together with fatty acid radicles and choline. They ■are found in nearly all plant and animal cells, but are especially abundant in the nervous tissues. They are essential cell constituents. As their name implies the derived proteins are sub- stances that have been formed from the naturally oc- curring proteins. Of these compounds the proteoses and peptones and the metaproteins are of particular importance since they represent stages of protein diges- tion. With a few exceptions proteoses and peptones are not found preformed in nature. These two groups of derived proteins are characterized by their great solubility. The peptones are sometimes looked upon as simple mixtures of rather complex poly- peptids. Carbohydrates 1 are especially abundant in the plant kingdom forming the chief mass of the dry tance of the plant structure. In the animal tissues they are found only in small quantities either in a free condition or in combination with proteins forming conjugated proteins. The carbohydrates serve as food for both man and animals and hence are of great importance from the standpoint of aliment. They contain the elements carbon, hydrogen, and oxygen, and the last two elements are usually in the same proportion that occurs in a molecule of water, namely 2 : 1, hence the term carbohydrates. All carbohydrates, however, do not have the hydrogen ami oxygen in this proportion, for a sugar, rhamnose, C,H 12 5 , has these elements in a different relation. Moreover, various organic acids have the elements hydrogen and oxygen in the proportion of 2 : 1 and yet are not carbohydrates. It is exceedingly difficult to give an exact definition of carbohydrates since they do not differ from main - other substances in many respects. Chemically the carbohydrates may be defined as aldehyde or ketone derivatives of polyhydric alcohols. The simplest carbohydrates are aldehyde or ketone derivatives of such alcohols, and the more complex members of this group of compounds may be regarded as anhydrides of the simple carbohydrates. The carbohydrates are generally divided into three chief groups namely, monosaccharides, disaccharides, and polysaccharides. Viewed from another standpoint they may be classified into sugars, starches, dextrins, gums and vegetable mucilages, and celluloses. The sugars are mono- and disaccharides and t he remaining groups belong under the division <>f polysaccharides. The mono- and di-nccharides are fairly soluble sub- stances possessing varying degrees of sweetness. In general the polysaccharides are more or less insoluble in the ordinary solvents. Mono- and disaccharides are given the ending "use" in accordance with the number of carbon atoms contained in the molecule. Thus, one speaks of a pentose, < . 1 1 , , , < > , , of a hexose, ( ',, 1 1 ,_,( >„, or of a heXobin i , ( II ._,»_>,,. (if tlie monosaccharides only the pentoses and hex oses are of practical significance in their relation to the food of man. The pentoses do not occur as such in nature but are formed by the cleavage of more complex molecules, the pentosanes, which are of a gum-like nature. The pentosanes are widely dis- tributed in the plant kingdom and are of great impor- tance as food for the herbivora. In man pentoses are absorbed and partially utilized but even when ingested in small quantities traces promptly reappear in the urine. The pentoses are of significance in human metabolism since they were first discovered in the animal kingdom by Salkowski and Jastrowitz in the urine of a morphine habitue\ They may also occur in traces in normal urine and in the urine of diabetics. A pentose is furthermore an integral part of certain of the nucleoproteins, and, therefore, may be isolated from organs rich in nuclear material, as for example, the pancreas, thymus, thyroid, spleen, and liver. This pentose is xylose and is the only one thus far separated from animal tissues. It is identical with the xylose obtained by boiling wood gum with dilute acids. Arabinose is a pentose that has been isolated from human urine by Neuberg. The hexoses are sugars and most of them occur in nature. They readily undergo fermentation with yeast, leading to the production of alcohol. They are either aldehydes or ketones and hence are termed aldoses or ketoses. Dextrose, an aldose, and levulose, a ketose, are found either free in nature or else may be formed by the hydrolytic cleavage of more com- plex carbohydrates or of glucosides. Such hexoses as mannose and galactose result only from hydrolysis of naturally occurring products C a ), for example, galactose is formed by the hydrolytic splitting of lactose, or milk sugar, or from hydrolysis of certain glucoside-like complexes, the cerebrosides, found in nervous tissue. Of the hexoses, dextrose and levu- lose are the most important. Dextrose ( = grape sugar = glucose) is found particularly abundant in the grape and also in company with levulose in various fruits, seeds, roots, honey, etc. Perhaps the most interesting feature in connection with dextrose from the standpoint of metabolism is that it is the sugar of the blood and lymph. It is present in minute traces in normal urine but may be found in large quantities in that voided by diabetics. Dextrose, and levulose, are capable of ready assimi- lation by the body without previous alimentary treatment, a statement wdiich in general does not apply to most of the other carbohydrates. Levulose ( = fruit sugar = fructose) is found especially distrib- uted in fruits and honey. It may be formed also in the hydrolysis of cane sugar and other more complex carbohydrates. In certain types of diabetes mellitus levulose may be eliminated in the urine. Dextrose and levulose have been so designated because of their influence upon the plane of polarized light, dextrose solutions causing a rotation to the right, levulose to the left. Glucosamine (chitosamine) is an amino derivative of dextrose. It was first prepared by Led- derhose from chitin by the action of strong hydro- chloric acid. It is also a cleavage product of several mucin substances and of proteins and may be re- garded as the connecting link between the proteins and the carbohydrates. All of the hexoses, because 205 Aliment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of their aldehyde or ketone structure, possess the property of reducing metallic oxides, of copper, bis- muth, etc. This behavior of the hexoses has been made use of for the identification and quantitative estimation of these substances. The disaccharides are divisible into two groups, those occurring preformed in nature, saccharose (= cane sugar = sucrose) and lactose ( = milk sugar), and those produced by hydrolysis of more complicated carbo- hydrates, maltose and isomaltose. The disaccharides are to be regarded as anhydrides, formed from two monosaccharides by the expulsion of one molecule of water. By the addition of one molecule of water, that is by hydrolysis, the disaccharides may be re- solved into two molecules of hexoses, thus: C 12 H 22 Il +H 2 0=C 6 H 12 6 -rC, ) H 12 O e Since the disaccharides all possess the same elemen- tary composition, C l2 H 22 O u , and the hexoses have the composition C„H i: ,O r , in common, the above reaction will apply to the hydrolysis of all the disaccharides. The hexoses yielded by the various disaccharides may vary, however, as may be seen from the following scheme. On hydrolysis Saccharose yields dextrose plus levulose. Maltose yields dextrose plus dextrose. Lactose yields dextrose plus galactose. This process of hydrolysis takes place along the en- teric tract so that all disaccharides ingested as food eventually are absorbed in the blood stream as mono- saccharides. Unlike the hexoses, saccharose does not reduce metallic oxides, whereas maltose, isomaltose, and lactose possess this power. All of the disaccharides exert a specific influence upon the plane of polarized light in common with the hexoses. Saccharose or cane sugar occurs widely distributed in the vegetable king- dom. It is found in the stalk of the sugar cane, in the roots of the sugar beet, in carrots and other vege- tables, etc. It is of exceedingly great importance as a food since the ordinary table sugar is pure saccharose. The mixture of dextrose and levulose produced by hydrolysis of cane sugar is termed "invert sugar"and the' process is called "inversion." Cane sugar is not directly fermentable by yeast. Ordinary yeast, how- ever, contains an inverting enzyme which transforms the saccharose into invert sugar. This readily under- goes fermentation resulting in the formation of alco- hol. Lactose is found only in milk where it occurs to the extent of three to eight per cent., varying with the type of animal. In the pregnant woman and animals lactose is sometimes found in the urine. It may also be eliminated through the kidneys during a stagnation of milk. Milk sugar is not fermentable with ordinary yeast but may undergo fermentation resulting in the formation of alcohol by the action of certain schizo- mycetes and the production of "kumyss" from mare's milk, or "kephir" from cow's milk. Maltose is ob- tained by the hydrolysis of starch induced by the action of diastase, saliva, or pancreatic juice, or from glycogen under certain conditions. It forms the fer- mentable sugar of the potato or grain mash, and also of the beer wort. In general, isomaltose occurs when- ever maltose is formed. Unlike the mono- and disaccharides the polysac- charides as a class are not possessed of a sweet taste. While a few are soluble in water most of them are not, although the latter may swell in hot water with- out visible change. The polysaccharides are all con- vertible into monosaccharides by hydrolytic cleavage. The chief groups of the polysaccharides are the starch group, gum and vegetable mucilage group, and the cellulose group. The polysaccharides all have the formula (C 6 H 10 O s )a;. Starch occurs as a white taste- less powder stored in various portions of the plant structure as reserve food. It is found chiefly in seeds, roots, tubers, and trunks. Starch may be quanti- tatively transformed into dextrose by hydrolysis with acids. Under the influence of amylolytic enzymes 206 starch yields a variety of dextrins, maltose, and a small quantity of dextrose. The various types of starch vary considerably in the character, that is, the shape and size, of the starch granules. Starch is incapable of utilization by the human organism unless it has been boiled. The starch grains are enclosed in a cellulose covering which is not dissolved by the enzymes of the alimentary canal. When starch is boiled with water, however, this cellulose membrane is ruptured and the starch grains are transformed into a paste which is readily attacked by the enteric en- zymes. Upon these facts as a basis rests the ordinary procedure of cooking vegetables containing consider- able quantities of starch. The herbivora, however, possess cellulose-dissolving ferments, hence raw starch can be well utilized by this class of animals. Inulin is a polysaccharide, in many respects similar to starch, which is found in many underground parts of plants, especially in roots and tubers. Enzymes have little or no action upon inulin, but levulose may be pro- duced from it by the influence of acids. Glycogen stands in a position between starch and dextrose and is an essential constituent of all animal cells, the largest quantities being found in the liver and mus- cles. The former organ is looked upon as the prin- cipal store-house for this material. The quantity of glycogen in the body at any time depends upon the food and the amount of muscular work performed. While it is conceded that protein and various other types of compounds may lead to a storage of glycogen it is well established that glycogen is most readily stored in the liver after large intakes of carbohydra The amount thus stored may reach twelve to sixteen per cent, of the weight of the liver. The degree of ac- tivity of the body also bears a direct relation to glyco- gen storage, since by hard muscular work, or by the en- ergy expended in shivering, 5 glycogen in the liver may be reduced to a minimum in a few hours. Starvation may bring about a similar result although less rapidly. L T pon hydrolysis with acid, glycogen yields dextrose, and maltose or dextrose may result from the action of diastatic enzymes in accordance with the type of enzyme employed. The dextrins stand in a close relationship to the starches and are formed as inter- mediate products from the latter in their transforma- tion into sugar by the influence of acids and enzymes. On the other hand the gums and mucilages occur ;ts natural products in the vegetable kingdom. The cel- lulose group comprises the mixture of carbohydrates constituting the cell wall of plants. The celluloses are characterized by their great insolubility in all ordinary solvents. It is probable that these substances are utilized by man to only an exceedingly limited extent. The fats constitute the third group of the organic food-stuffs. These substances are widely distributed in both the animal and vegetable kingdoms. In the latter the fats occur in the seeds, fruits, and in certain instances, in the roots. All animal tissues and organs contain fat, although the quantity present in th( different structures may vary greatly. There are three principal deposits of fat in the animal body. namely, in the intermuscular connective tissue, tie fatty tissue in the abdominal cavity, and the sub- cutaneous connective tissues. Chemically the so-called neutral fats are esters of fatty acids and an alcohol, usually glycerol. Those esters are triglycerides, that is, the hydrogen atoms of the three hydroxyl groups of glycerol are replaced by the fatty acid radicles. The chief animal fats are mixtures of the esters of stearic, palmitic, and oleic acids. In addition glycerides of such fatty acids as butyric, caproic, caprylic, and capric acids occur in considerable amounts in the fat contained in milk. Less well known are the esters of lauric, myristic, and arachidic acids which are usually present in small quantities in animal fats. The triglycerides of lauric, myristie, linoleic, erucic acids, etc., sometimes are found in great abundance in the plant kingdom. REFERENCE HANDBOOK OF TIIK MEDICAL SCIENCES Allmrnt i,. three most common animal fats present varying erees of hardness, tristearin being the hardest, olein a liquid at ordinary temperatures, and tri- Imitin occupying a position between the two. The riable hardness of animal fats depends upon the iantitative relationships of these three triglycerides. impaled with the carbohydrates fats are poor in ;ygen. The fats are soluble in ether, carbon bisul- ilde, chloroform, benzene, etc., but are insoluble in 1 1 ei ■. The color, taste, and odor of fal from different iinvs are due to contaminating substances, since ire fats are colorless, tasteless, and odorless. The ts give a temporary emulsion when shaken with iter, but when shaken with an alkali or a soap the nulsion is permanent. The fats may be split into ,-ir component parts, glycerol and fatty acids, by e addition of the components of water in accordance ith the following reaction, where R represents any i iv acid radicle: C 3 H s (OR) 3 + 3H : 0=C 3 H 5 (OH) 3 + 3HOR 'lis process is called saponification and may be i niially induced by pancreatic lipase and other uiilar enzymes of the plant and animal kingdoms. may also be brought about by the action of steam iilcr pressure; by long continued contact with air id lignt; and finally by treatment with an alkali, i the last instance soaps result and this reaction is ie underlying principle in soap making on a com- ercial scale. In addition to the naturally occurring fats advan- ige has been taken of the varying melting-points of ie principal fats to make artificial mixtures on a immercial scale as substitutes for butter. Thus eomargarine is the name given by law to these liter substitutes in the United States. By heating ief suet to its melting-point, cooling slowly and tbjecting the warm mass to pressure in a filter press, ie softer portions consisting mainly of triolein and ipalmitin, may be separated. The soft portion is nown as oleo oil, the hard part as beef stearin. The loo oil is the material most often employed under the ;itne oleomargarine. A similar mixture is made by imbining cotton seed oil with beef stearin. Some- mes the fats are churned with a certain amount of al butter to furnish a product with a flavor sugges- ve of butter. The name butterine is given to such lixtures and from the standpoint of food they are illy as wholesome and nutritious as butter. 7 Closely related to the fats stands a group of sub- lances known as lipoids. They are similar to the .is in physical properties, but differ from them in lictnical structure. Cholesterol, a monatomic aleo- • il, C 26 H. 5 OH, is undoubtedly, of importance in the utritional rhythm, although its exact significance is ot definitely known. Its wide distribution in nimal fluids and tissues and the occurrence of closely lied compounds, the phytosteroles, in the plant ingdom is indicative of the significance of this group l substances in life processes. Of special importance - another group of compounds included under the P = CH-O/ I N 'CH, "CH. CH, I mm the st rue t urn I 1 01 inula given abo\ e it is evident that there may be various types of lecithins in correspondence with the fatty acid radicle or radicles contained in the molecule. '| he phosphatides are widely distributed, being especially abundant in the brain and other nervous structures, in the yolk of the egg, and in the muscles. The phosphatids, and especially the lecithins, are of the greatest importance in the development and growth of living organisms for they serve to build up the complex pnosphorized nuclein substances of the cell and cell nucleus. Wood, as eaten by man and animals, is a natural mixture of the various food stuffs described. Seldom are the isolated principles eaten by themselves, other than in the case of sugar and salt, or pure fat. It is the function of digestion to separate the individual principles from this natural mixture, by which means they are separately absorbed. The behavior of animal and vegetable' food is quite different in the alimentary canal, which difference is dependent more upon the quality of dry substance contained in the latter food than upon its quantity. Vegetable food yields a much larger percentage of indigestible residue, and is in itself much less easily digestible, owing to the fact that it is more or less enclosed in the difficultly soluble cellulose, while animal food is free. More- over, vegetable food, as a rule, is less easily absorbed, and, as it contains usually a less percentage of nitrogen, a much larger quantity is needed to furnish a certain amount of this element than in the case of animal food. Again, the large quantities of starch contained in a vegetable diet tend to produce an acid fermentation in the small intestines, with formation of butyric acid, together with marsh gas and hydro- gen, which causes the frequent intestinal excretions of herbivorous animals. Nearly all foods contain appreciable amounts of water and inorganic salts. That these are essential to the well being of the organism has been demon- si rated repeatedly. For the present it will be suffi- cient to note that the chief mineral substances needed by the organism are the four elements calcium, so- dium, potassium, and magnesium, which exist in com- bination with four acids, namely, phosphoric, hydro- chloric, sulphuric, and carbonic. The different nu- trients are found in nature in a variety of combina- tions or admixtures. Milk contains all the types of food stuffs, whereas in lean beef the carbohydrates and fats may be present only in small quantity, although the protein content is large. On the other hand, cer- tain types of vegetables, as the potato, contain only small amounts of protein and little or no fat, but the carbohydrates are present in large quantity. In gen- eral, foods of animal origin are particularly rich in protein and fat. Usually carbohydrates are abun- dant in vegetable foods. In the Table II., p. 208, is given the relative distribu- tion of the various food stuffs as they occur in the edible portion of the natural products. In a determination of the food value of a given food stuff, or of a given diet composed of a mixture of food stuffs, it is necessary to ascertain its chemical compo- sition with special reference to the content of protein, fat, carbohydrate, and inorganic salts; its caloric or heat value; and lastly its digestibility or availability. In an ordinary mixed diet, protein matter is usually present in the proportion of one part to about five parts of non-protein matter — i.e. fats and carbohy- drates. The proportion of fat to carbohydrate is usually exceedingly variable, ranging anywhere from one part of fat to from five to twelve parts of carbo- hydrate. While these statements are to be accepted as a general expression of the ordinary proportion of the three primary varieties of food stuffs contained in an average diet, it is to be remembered that the element of cost or the ease of procuring frequently determines the relative amount of the three classes of food stuffs in the daily diet. Thus, in countries where 207 Ailment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES meat is plentiful, as in South America, protein food is consumed in much larger proportion than above, whereas, in some Asiatic countries, the prevalence of rice, cereals, and fruits leads to a daily diet in which non-protein foods are especially conspicuous, and the proportion of protein is reduced to the minimum nec- essary for life. Further, for similar reasons, the ratio of fat to carbohydrate undergoes wide variation among different races or in different countries. Thus, in the far north, fat (animal) constitutes the greater pro- portion of the non-protein part of the diet, while in countries where cereals abound, carbohydrates, mainly in the form of starch, make up the greater portion of the non-nitrogenous food. Regarded from a broad viewpoint the human body needs food for three purposes, namely, for growth and development, to replace wornout cellular mate- rial, and finally to furnish energy for vital activities. Nitrogen is particularly necessary for the purpose of cell repair, and food should be of such a nature that it will readily yield its potential energy. Proteins are the only food stuffs capable of supplying the nitrog- enous need, whereas all types of food stuffs will yield energy in varying degree. The older view that the proteins were to be regarded as tissue formers and the carbohydrates and fats as energy yielders has been discarded. The prevalent view at present is that the body is not restricted to the use of any one food stuff for a particular purpose, but it may make use of all types in order to employ the energy of all nu- trients in an economical manner. "Thus, the carbo- hydrates, fats, and proteins stand in such close mutual relations in their service to the body that for many purposes we may properly consider the food as a whole with reference to the total nutritive requirements, provided a common measure of values and require- ments can be found. Since the most conspicuous nutritive requirement is that of energy for work of the body, and since these organic nutrients all serve as fuel to yield this energy, the best basis of comparison is that of fuel value." 9 Energy may be measured in terms either of heat or of mechanical work. The energy available in the food stuffs is expressed by its heat or fuel value, that is, in units of heat, or calories. In accordance with this unit it has been demonstrated that one gram of protein has a heat value of 4.1 large calories; one gram of fat will yield 9.3 large calor- ies, and the heat, or fuel value of one gram of carbohy- drate amounts to 4.1 large calories. The total fu'ei value of a few of the common food stuffs is given in Table II. The conditions which most obviously influence the food requirement with respect to fuel value are age size of body, and muscular activity. 'When a man is at rest, that is, with all external muscular work excluded, it has been estimated that approximately 2.UU0 calories per day are necessary for proper nutri- tional rhythm. Such an energy requirement lias been called the maintenance requirement. Of this about eight to twelve per cent, is expended upon the work of digestion and assimilation, five to ten per cent, upon the circulation, ten to twenty per cent, upon the respiration and thirty to fifty percent, upon the maintenance of muscular tension or "tone." Muscular work is the most important factor in raising the energy requirement above the maintenance Deed. Thus a man who works at manual labor may inn his metabolism by 1,000 to 2,000 calories per day above what is needed for maintenance at rest, making his total food requirement 3,000 to 4,000 calories per day, although with severe labor this may rise to 6,000 calories or even higher. Voit estimated the food re- quirement of a moderate worker at 3,050 calories, and Atwater in the United States believed that the American needs 3,400 to 3,500 calories per day. By moderate worker was meant a man engaged in manual labor for nine to ten hours a day, such as a carpenter or a mason. It is well recognized that the calorific need varies directly with the severity of the muscular exercise, and in accordance with this idea Tigerstedl has estimated the energy requirements sufficient for individuals engaged in a variety of occupations. Thus, 2,001 to 2,400 calories suffice for a shoemaker. 2,401 to 2,700 calorics suffice for a weaver. 2,701 to 3,200 calories suffice for a carpenter or mason. 3,201 to 4,100 calories suffice for a farm laborer. 4,101 to 5,000 calories suffice for an excavator. Over 5,000 calories suffice for a lumberman. In a general way the total food requirement varies with the body weight. This is not strictly true, for the food requirement though greater in absolute amount in the larger individual is less per unit of body weight Table II. Composition of Edible Portion- of Some Common Food Materials. 8 Food materials. Water. Protein. Carbohydrate. Fat. Mineral matter. Fui 1 value per pound. Per cent. 73 8 54.6 67.1 S3 . 6 74.8 55.5 SS.3 73 7 11.0 79 2 53 , 5 58.5 Per cent. 22. 1 15 8 19.4 15 3 2 1 . 5 21.1 6.0 13 4 1.0 17 6 25 I 11.1 Per rent. Per cent. 2.9 28.5 12.7 26.2 22 9 1 .3 10.5 S5.0 1.8 3 2 100 4.0 33.7 Per cent. 1 .2 0.9 0.8 4.9 1.1 1.0 1.1 1.0 3.0 1.7 24 7 0.8 i 'alories. ;30 1 495 91)11 1395 505 Turkey Fresh oysters, s ilid 1360 3 .; 720 Butter 360.5 ■in:, 411) 215 Milk 87 l) 34.2 3.3 25 . 9 5.0 2 4 100.0 56 7 73 1 22 65 . 9 19 7 16 9 IS 4 17.3 6.9 (1 7 3.S 325 1950 29 _' 5.9 68.5 10 I 75 1 74.6 78.3 4.S 6.4 8.9 9.8 7 1 18 1 3 1 7.7 2.2 21.0 33.9 4.1 9.1 7 1.5 1 1 0.5 0.1 54.9 49.4 1 1 2 1 1 7 4.1 0.7 1.0 1.0 2.0 3.4 1925 Fresh lima beans :,7I) 1625 -179 165 385 3030 2845 208 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ailment than in the smaller. The energy metabolism increases in proportion to the surface rather than with the weight. However, in the human species the variation in size is relatively not very great and for all practical purposes the statement is essentially correct that the greater the weight the greater is the energy require- ment, cither tilings being equal. Fur the young the ,1 requirement is relatively greater than in the adult even when calculated according to the unit surface of body. It is probable that the period of growth has a distinct influence on the extent of metabolism and for this reason the food of children should furnish ample fuel value to compensate for the more active general metabolism. In old age metab- olism is much reduced, being lower than in an in- dividual of medium age, hence the food requirement is correspondingly diminished. The question as to what extent sex especially influences the food require- ment cannot be said to be definitely established. During life cellular material is constantly undergoing disintegration as a result of life processes, thereby creating a constant demand for the elements that titute the cellular structures. In a large measure the underlying basis of these structures is nitrogenous rial, or protein. Hence, the need for food pro- tein is in direct proportion to the destruction of the nitrogenous structural elements of the organism. Under ordinary conditions of life, work is not done at tin 1 expense of the nitrogenous constituents. Ex- pressed in other words, muscular activity is not per- formed as a result of the combustion of protein ma- terial composing the muscles. Work is done by the organism preferably by the energy liberated during the combustion of the non-nitrogenous substances, the fats and carbohydrates. In the absence of a sufficient supply of the last-mentioned compounds protein material, for example, that of muscle, may e as the source of energy and, therefore, under these circumstances work may be done as a result of protein disintegration. There are only a few condi- tions under which a storage of protein occurs in the body, and even under these circumstances storage be merely transitory. Nitrogen may be stored (a) in the growing body (or in pregnancy) where tissue is being constructed; (/<) in cases where ased muscular exercise calls for enlargement of muscles; (r) in cases where, owing to insufficient food intake, or to wasting disease, the protein content of the body has been more or less diminished and conse- quently any surplus available is utilized to make good the loss. It follows from these facts, therefore, that any huge excess of protein over the actual daily need for tissue reconstruction is probably uneconomical physiologically. Although protein may furnish gram for gram as much energy as carbohydrates its utilization as a source of energy is attended by a great more difficulty than is true for the carbohydrates. The latter are usually easily digested and are entirely assimilated whereas protein disintegration, which isential in order to make available potential energy contained therein, is a much more protracted process, finally resulting in the necessity for increased activity on the part of the kidneys so that the non- available nitrogenous products may be eliminated. The exact amount of nitrogenous food necessary for man per day is difficult of determination and is a matter upon which has been based a great deal of i Dntroversy 10 . An idea of the normal dietary need is probably best obtained by an experimental determina- tion of how much protein must be contained in the food in order to keep the body in protein or nitrogenous equilibrium. This is done by striking a balance between the nitrogen of the food ingested and the nitrogen eliminated in the excreta. A plus balance indicates a storage of nitrogen in the body; a minus balance shows a loss of body protein. When the balance is approximately zero the body is said to be in protein or nitrogenous equilibrium. From a Vol. I.— 14 long series of investigations it has been concluded that the body may so adjust itself in a short period of time that nitrogenous equilibrium may be estab- li bed on widely varying quantities of protein. Thus the same individual may exhibit nitrogenous equilibrium on -even grams of nitrogen in the form of protein or on thirty grams or even more. The fuel value of the food lias a great influence upon the- ex- tent of protein metabolism by determining whether the body must draw' upon its own tissues for fuel. Under these circumstances it is readily conceivable that non-nitrogenous food -luffs play an important role in the establishment of nitrogenous equilibrium. other things being equal it is much easier to get an individual into a condition of nitrogen equilibrium when the fuel value of the food is ample than when the energy yield is small. That tissue protein catabolism may be greatly diminished by intake of carbohydrates and fats has long been known and this action has been designated as their "protein sparing'' effect. Thus the loss of protein from the tissues which occurs with an insufficient diet may be de- creased or even entirely stopped by adding carbo- hydrates and fats to the food. If these substances are added to the diet of an individual in nitrogen equili- brium a temporary storage of protein may occur. Up to a certain point the fats and carbohydrates are inter- changeable m isody nan lie quantities, that is, one gram of fat is isodynamic with 2.2 grams of carbohydrate, beyond this point, which may show marked variation for different individuals, fat is not well utilized. Carbohydrates tin- easily utilizable, fats with more difficulty. The gastroenteric tract rebels at large quantities of fat. This statement is especially true for most civilized peoples though exceptions may be found, as in the Esquimaux and certain savage tribes. On the assumption that energy is supplied suffi- cient to meet all the ordinary demands, how much pro- tein or nitrogen must the daily food contain in order to maintain the organism in nitrogenous equilibrium and in a general condition of well being? Among other investigators Siven has attempted to answer this query. Siven with a body weight of sixty kilos experimenting upon himself found that with sufficient fuel value he was able to maintain nitrogen equilib- rium upon thirty-nine grains of protein per day. The most extended and thorough series of investiga- tions upon this point were those carried through by Chittenden. 11 Professional men, athletes, and soldiers of the United States Army acted as subjects. In the following table are given a few examples of the results obtained. Table III. TmtalFcel Valce, Protein- Intake and N'itrogex Balance per Day. Subject. Body weight. Fuel value. Protein. Nitrogen balance. C Kilos. .",7 70 01 61 04 64 60 02 7."» Calories. Grams. 1,613 40 n Gram. + 165 VI. . 2,448 2.00.S 2,152 2,509 2.S40 2.S40 2.4.-.0 2,809 53 2 55 2 63.1 59 4 53.9 54 . 2 55 2 71 7 4-0 38 u 4-0 158 Bo... + 34 O(I) 0(11) Br + . S09 -0 2' 12 + 1 5 ! P 4-0.089 S 4 339 It is apparent from these data that nitrogenous equilibrium may be established and maintained by men weighing between fifty-seven and seventy-five kilos upon an ingestion of protein per day varying 209 Aliment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES from forty to seventy-two grains without appreciably increasing the fuel value of the food ingested. The figures, however, probably represent the minimum quantity of protein compatible with nutritional rhythm and continued vigor,. On the other hand, custom and habit have played a role in the establishment of so-called dietary stand- ards. 11 '! Thus Voit in Germany, by estimation of the food eaten by the ordinary individual, set up a standard whereby the organic food requirement should approximate: IIS grams protein. 5G grams fat. 500 grams carbohydrates. These quantities of food-stuffs would furnish about 3,000 calories. Playfair in England promulgated the following standard: 119 grams protein. 51 grains fat. 531 grains carbohydrates, which would yield a fuel value of 3,000 calories. In France Gautier proposed a standard for men with little muscular work as follows: 107 grams protein. 65 grams fat. 407 grains carbohydrates. The fuel value of this dietary would furnish 2,630 calories. Langworthy has collected the data of large numbers of dietaries of families under diverse conditions both in the United States and abroad, and stating them in terms of protein and calories per man per day has compiled the following table. Table IV. Langworthy's Compilation of Results of Dietary Studies. 12 Food per man Occupation of head of family. per day. Protein Fuel value grams. cal< tries. United States: Man at very hard work (average 19 177 6,000 studies). Farmers, mechanics, etc. (average 162 100 3,425 studies). Business men, students, etc. (average 106 3,285 51 studies). Inmates of institutions, little or no mus- S6 2,600 cular work (:iv<-ruge of 49 studies). Very poor people, usually out of work 69 2,100 (average 15 studies). Canada: Factory hands (average 13 10S 3,480 studies). 89 2,685 108 3 228 9S 3,107 German v: 134 3,061 Professional men 111 2,511 110 2,750 Japan: 118 S7 4,415 2,190 At 3,-100 112 2,825 108 2,812 In addition to the foregoing functions of the non- nitrogenous food stuffs these substances may be of service to the body in other ways. Thus although fats are especially important for the fuel value they furnish, they form the basis of adipose tissue and are essential for tissue development generally. The great importance of fat in food and of that deposited in the body is to be found in the aid which it furnishes to the hungry organism in developing its wasted tissue. A purely protein diet for a person poor in fat necessitates a large amount of the former to sustain the weight of the body, indeed more than the intestines are capable of absorbing. But a mixture of fat and protein diminishes protein metabolism. It is not possible to convert a poor body into a body rich in fat and protein material by an exclusive protein diet; fats or carbohydrates are needed, admixture of which diminishes the work of the organism. Carbohydrates, without doubt are in a large measure the source of fat in the body. Sugar or starch is always present in fattening foods and although there is little evidence of a positive nature that fat is formed directly from carbohydrate there is a close relationship between carbohydrate intake and fat deposition in the organism. It has been suggested that carbohydrate functions by protecting the fat already deposited. It does this by under- going combustion instead of the fat. Collagenous tissue, comprising the gelatinous principles (organic basis of bone, cartilage, tendons, and connective tissue), cannot supply the place of the true proteins; still, Voit has found that nitrogen- ous equilibrium is established at a lower level of protein food when gelatin is added. The value of gelatin has been found by Murlin 13 to be dependent to a high degree upon the protein condition of the body, on the calorific value of the food and the quan- tity of carbohydrates in the latter. When two-thirds of t lie total calories partaken of were in the form of carbohydrates, gelatin could supply sixty-three per cent, of the total nitrogen. Gelatin may also some- what decrease the consumption of fat, although it is of less value in this respect than the carbohydrates, Water is of exceeding great importance for the well being of the organism. According to Voit, the body of a fully developed man contains sixty-three per cent, of water, while the body of a growing child contains nearly 66.5 per cent. Any great alteration in the content of water in the animal body is always attended with disastrous results; thus, in diarrhea, cholera, etc., such large quantities of water are lost as tn render the blood quite thick, and even the muscles may lose as much as six per cent, of water. Such loss, if long continued, soon results in loss of vitality and consequent death. It is noticeable, moreover, that a certain proportion of the water contained in the tissues of the body can be removed without difficulty, while a smaller, residual portion, apparently more closely united to the organic matter, can be separated only with great difficulty; this is well illustrated in the simple drying of dead muscle tissue. Removal of the water from low forms of animal life, by drying them at the ordinary tempera- ture, or at a temperature below the coagulating point of their body protoplasm, causes them to lose all appearance of life; but in such condition they will again absorb the water lost, and return to their former appearance and vitality. Increase of water in the organism beyond the normal amount is usually associated with an unhealthy condition of the body. Various investigators have likewise demonstrated t hat there is a close connection between the percen of water in the body and the diet, irrespective of tin' water taken as drink. Thus Voit has shown that a bread diet, continued for some time, renders the body more watery than normal. In one experiment with a cat, the amount of water in the brain and muscles was increased three to four per cent. Increase of fat in the body is usually attended with a diminished percentage of water. A vigorous, well-nourished man possesses organs much poorer in water than a badly fed person. Forster 14 nas figured that under 210 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aliment normal conditions a person living on an average diet alces daily from 2,215 to 3, 538 grams (about 6.5 pounds ivoirdupois) of water. It is easy to see, however, i a great variety of circumstances, as variations ,i diet, exercise, temperature, etc. may have a modifying influence on the amount of water taken i to the system during the twenty-four hours. The just given do not, however, represent all of the water, since a variable amount is formed within [he body by oxidation of tin- hydrogen contained in organic food -stuffs. Tims, according to Voit in case of a hungry man. thirty-two grams of hydro- in the form of organic matter were oxidized to 288 us of water during twenty-four hours. It is thus plainly evident from tin' Ion going that er is a necessary constituent of the body, and as . of the food-stuffs is a decidedly important one; are need to understand its true significance. It - not itself undergo any chemical change, and is it source of energy, though it aids chemical ige in supplying by its presence a condition Mutely necessary for its occurrence in other bodies. The mineral matters are more closely concerned in the structure of the organism than in the liberation of energy, and this is true both of animal and vege- table organisms. Further, inorganic salts appear to . > an important part in regulating and controlling line measure the various metabolic processes oi the body although they themselves contain little or no potential energy. They maintain a normal com- ii. m and osmotic pressure in the liquids and ues of the body, and by virtue of their osmotic ~ure they play an important part in controlling low of water to and from the tissues. Moreover, • salts constitute an essential part of the com- position of living matter. They are bound up in the re of the molecule in an intimate manner and are necessary to its normal irritability. The proteins of the body fluids contain definite amounts of ash if this is removed the properties of these sub- ire greatly changed. They are particularly ssary in the developing animal body. Mineral ter is needed not only for the growth and nutrition of the skeletal port ions of the body, but it is also needed in the structure of the softer tissues, as well as in formation of secretions; thus, the acid of the lie juice has its origin in the chlorine of sodium i!e, or common salt, while the alkalinity of the pancreatic secretion, as well as that of some of the er fluids of the body, is due mainly to inorganic salts, as the alkali phosphates and perhaps bicarbon- ates. In many juices of the body, inorganic elements arc held not only in solution, but quite firmly united i the more characteristic matter, as in the sodium salts of the bile acids, and in some instances they can be removed only by decomposition of the compound. The excess of salts taken into the body, by the food or other means, and that which becomes free by imposition within the body, is easily removed througn the urine and feces. There is still other evidence that the various inorganic salts of food serve definite purposes in the body." The two alkalies, potash and soda, so widely distributed (for distribution of sodium and potassium in some common foods see Table V.) and so closely allied in their chemical properties, cannot be made to replace each other in the living organism, while the same is likewise true, to a certain extent, of the alkali earths, lime and magnesium. Thus a qualita- tive, and also a quantitative, selection of inorganic matter is noticeable in the body, particularly in the blood, where the corpuscles contain the greater por- tion of the potassium salts and phosphates, while in the serum, sodium salts and chlorides are in excess. Again, it is quite noticeable that potassium salts predominate in the formed tissues of the body, while sodium salts are characteristic of the fluids. I orster's experiments on pigeons with food poor in salts, and on dogs u jth powdered meat from which the greater portion of inorganic matter had been ii moved by extraction with hot water, fat and carbo- hydrates being afterward added, showed that these animals could not bear the loss longer than four to live weeks without great suffering, and, finally, death. In fact, it is evident, from physiological experiment, that an organism supplied with all organic food -tell and water can live only for a limited time without mineral matter. For a time the body draws upon tin' inorganic matter stored up in it- own tissue: but this failing, and that naturally present in the organic f Is being removed, death soon results from lack of inorganic aliment. In the ordinary diet of men and animals, sufficient salts are generally contained in the non-nitrogenous and proteid foods to furnish the required amount of mineral matter. As to the actual quantity of inorganic mat ter needed to counter- balance that withdrawn from the hotly in twenty- four hours, we can hardly say. The eight elements, iron, calcium, magnesium, po- tassium, sodium, chlorine, sulphur, and phosphorus, constitute the so-called ash of our foods, in other words, the inorganic food-stuffs. Iron may be looked upon as the link connecting the organic and inorganic food stuffs to the body com- pounds. This element is an integral part of hemo- globin and other compounds associated with the proc- esses involved in oxidation, secretion, reproduction, and development. The iron contained in these sub- stances is in a firm organic combination with proteins. These organic compounds of iron are probably in turn constructed from somewhat similar iron-con- taining groupings in the food-stuffs. Numerous in- vestigations have been carried through to determine the influence of various preparations of iron upon the storage of this element within the organism, with the general conclusion that the iron of naturally occurring food-stuffs best serves the purpose of recon- struction of hemoglobin within the body. It has been estimated that approximately ten to fifteen milligrams of food iron are sufficient to maintain an average man under normal conditions in iron equilib- rium. In the typical food-materials iron exists in varying quantities (see Table V.). In meat iron occurs largely in hemoglobin retained in the muscle tissue. The iron present in milk, eggs and the vegetable foods is perhaps better absorbed and assimilated to greater advantage than the iron of meat. In the grains a great portion of the iron exists in the germ and outer layers. Hence, in the process of milling this iron is rejected so that fine flours are less rich in this element than the natural cereals. Vegetables and fruits contain appreciable quantities of iron which man undoubtedly utilizes to the best possible advan- tage. Foods containing little iron are fat pork, bacon, lard, butter, salad oils, sugars, starches, and confec- tionery. Iron is eliminated from the body chiefly through the intestine. Of the calcium salts ingested only about one-tenth is excreted through the kidney. Like iron this ele- ment is eliminated from the body through the intes- tinal wall and so passes out with the feces. If ani- mals are kept for long periods of time upon diets poor in calcium, marked wasting of lime salts from the bones may occur. This is especially true for the young growing individual in whom the symptoms of an inadequate supply of calcium salts are chiefly mani- fested by abnormal weakness and flexibility of the bones. Herter 10 ascribes to insufficient assimilation of calcium in the food many cases of arrested develop- ment in infancy. The calcium requirement has not been definitely established, although it is probable that the ordinary healthy man needs about 0.7 gram calcium oxide per day to maintain calcium equilibrium. Calcium occurs chiefly in the skeleton as calcium phos- phate and carbonate. It is these salts that give 211 Aliment REFERENCE HANDBOOK OF THE MEDICAL SCIENCES rigidity to the bones. Of the calcium in the body about ninty-nine per cent, is found in the bones and the remainder is distributed, partly in organic com- bination with the proteins, and partly in solution in the blood and other body fluids. Calcium salts are especially necessary for the coagulation of the blood and are of prime significance for the normal action of the heart muscle. Moreover, calcium plays an important role in regulating disturbances in inorganic equilibrium. "Calcium is capable of correcting the disturbances of the inorganic equilibrium in the animal body, whatever the directions of the deviations from the normal may be. An abnormal effect which sodium, potassium, or magnesium may produce, whether abnormality be in the direction of increased irritability or of decreased irritability, calcium is capable of reestablishing the normal equilibrium." 17 The occurrence of calcium in some of the common foods may be seen from an inspection of Table V. It will be noted that milk is particularly rich in this element. Beef and flour are much poorer in calcium. Other cereals which have undergone the milling process contain less calcium than the whole grain-. ample, phenol, cresol, indol, skatol, in a form which is known as an "ethereal or conjugated sulphate." Table V. shows the distribution of sulphur in a few common foods. Phosphorus is an essential cell constituent and as such is found distributed throughout every tissue and fluid of the body. Phosphorus occurs in foods chiefly, in four forms; (a) in the proteins, as nucleoprotein of cell nuclei, lecithoproteins, and phosphoproteins as exemplified by casein and vitellin; (b) in the phos- phatides, as the lecithins; (c) as organic derivatives of phosphoric acid (inosite phosphoric acid ester) of which the salts occurring naturally in wheat are called "phytin"; and (d) inorganic phosphates which are found in abundance in most foods. Phosphorus is absolutely necessary for normal nutritional processes and to maintain phosphorus equilibrium approx- imately one gram of phosphorus is required per day. For the reconstruction of nuclear material of cells phosphorus is essential, and the problem has ari-cn whether for this purpose organic or inorganic phos- phorus is demanded. It is probable from recent ex- periments' 9 that the organic phosphorus constituents Table V. Ash Constituents of Foods in Percentage op the Edible Portion. ls Food. CaO. MgO. K-O. Najtl. r ii ci. Fe. Almonds Apples Asparagus Bananas Lima beans, fresh . . Beets Cab] >age Carrots Celery Corn, fresh Eggs Codfish Lean beef Milk Oatmeal Wheat flour Peas, fresh Potatoes Rice Squash Turnips Walnuts Wheat, entire grain 30 .35 014 .014 04 .02 01 .04 04 .11 03 .033 068 .026 077 .034 10 .04 nils ii.-,.', 09S .01.-) (II. - ) .03 nil .04 16S .019 13 .212 025 .1127 04 .07 016 .036 012 .045 02 .01 089 .028 108 . 237 061 .213 20 .03 15 .02 20 .01 50 .02 70 .12 45 .10 45 .05 35 .13 37 .11 137 .05 165 .20 40 .13 12 .09 171 .038 158 .109 146 .04 30 .04 53 .025 084 .028 05 .05 40 .08 44 .03 519 .mis .87 .03 .09 1 1.-,;, .27 .09 .09 .10 .10 22 .37 .40 .50 .215 .872 .20 .26 .140 . 203 .OS .117 .902 005 .135 .002 004 .005 .0003 04 .04 .0010 20 .013 .0006 009 .06 .0025 04 .015 .0006 03 .07 0011 036 (122 .0008 17 1125 ;> 014 .044 .0008 10 .19 .003 24 0004 05 .20 0038 12 .033 . 00024 035 .215 .0036 07 .17 .01115 01 .06 .0016 03 .03 .0013 05 .105 .0009 01 .026 in ins 04 .07 . 000.5 01 .195 .0021 OS .17 .0053 In general fruits and vegetables contain fairly large amounts of this element. This is particularly true of the fresh vegetables. It is apparent, however, that in order to insure to the body an abundance of available calcium the dietary should include an ample supply of milk. Our knowledge concerning the functions of mag- nesium in the body is vague. Beyond the fact that this element is a constituent of practically all the tis- sue-; and fluids of the body, especially of the bones and muscles, and that in general calcium and mag- nesium appear to be antagonistic little is definitely known. For the distribution of magnesium in a few foods see Table V. Sulphur occurs chiefly in the body in combination with proteins and as such it gains entrance to the organism, although some sulphur in the form of sul- phates may also be ingested with the food. In the disintegration of the protein materials incidental to their assimilation, sulphur is oxidized to sulphuric acid which is neutralized as rapidly as it is formed by one of the basic elements and in this form is elimi- nated by the kidneys. A smaller portion of the sul- phuric acid formed is combined with an organic radicle, usually but not necessarily derived from putrefactive processes in the large intestine, for ex- 212 of the cells may be satisfactorily constructed from the ingestion of inorganic phosphates, although it is also undoubtedly true that the organism has a prefer- ence for phosphorus in organic combination. Table V. gives the content of phosphorus in a few f Is. These figures do not indicate the nature of the phos- phorus compound present and it is possible that the four types of phosphorus compounds mentioned above are not equally available for the restoration of body phosphorus. Phosphoproteins and phosphatides arc particularly abundant in eggs. In milk both phos- phoprotein and inorganic phosphates are found, Meats and fish contain phosphorus chiefly in the form of inorganic phosphates. The salts of phytic acid, collectively designated " phytin " are present in largest quantity in both the inner and outer portions of the various grains. Condiments. — Under the general term of accessory articles of diet are classed the condiments, flavors, and stimulants. These substances are included in the diet to increase the attractiveness of our food and although in general they may impart a certain amount of energy to the organism by their oxidation they are of nutri- tional importance for entirely different reasons. The condiments and flavors function by giving to the food a sufficient degree of palatability which in turn by the REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alimi'iit so-called psychical stimulation facilitates gastric se- cretion. Some of these substances may have an additional value in that they increase the rapidity of absorption from the stomach. Gautier 20 has divided the condiments into the following classes: (1) Aro- matics, comprising vanilla, anise, cinnai i, nutmeg, and other similar essential oils; (2) peppers; (3) the alliaceous condiments, garlic, mustard, etc.; (4) the acid condiments, vinegar, citron, pickles, etc. ; (5) the condiments, such as table salt : (6) the sugar condi- I rider the head of stimulants are included hoi, tea, coffee, cocoa, chocolate, and meat extracts. ol. — The alcoholic, drinks contain from forty to sixty per cent, of alcohol, as in rum, brandy, and whisky, to from two to ten per cent., as in beer and wines. Malt liquors contain, perhaps, the largest iber of constituents, among others there being ii-, dextrin, gluten, and various substances from hops. The exact value of alcohol-' 1 as a food, broadly considered, is uncertain. Experiments, care- fully made on man, however, clearly show that when rale amounts of alcohol are ingested, the alcohol is burned up in the bodj- — i.e. oxidized like any non- ogenous food. The potential energy of the alcohol is transformed into kinetic energy, and consequently hoi h to be considered as having some food value. it may, therefore, be classified with the non-nitrogen- ous foods. Further, as a non-nitrogenous food, alcohol replace an isodynamic amount of fat or carbohy- drate in the diet without change in the balance of income and outgo. Alcohol serves to protect body protein and fat from oxidation; i.e. like a typical non-pro- tein food it diminishes the oxidation of tissue protein by being itself oxidized. These facts, however, do not imply that alcohol is necessarily a desirable food or that it is physiologically economical. It is to be remembered that, prior to its oxidation in the body, alcohol may produce deleterious effects of various kinds, more than counterbalancing any gain which may result from its oxidation. It may likewise give rise to changes, either directly or indirectly, in the various metabolic processes of the body, which must of necessity influence more or less its value as a food. Moreover, the danger entailed when the dose is too large prevents its ready acceptance as a practical food-stuff. On account of its easy absorption it has f't d suggested, however, as a useful substitute for the solid, non-nitrogenous food-stuffs in sickness. There are many reports of cases where alcohol has served as the principal nutriment during the critical periods of fevers and in other conditions which would tend to lend support to the above suggestion. There are also results upon diabetic patients which indicate that in this condition alcohol used as a food dimin- ishes the production of acetone bodies and protects the protein. Alcohol has a direct and an indirect influence upon the secretion of gastric juice. In this direction it acts as a stimulant. It likewise stimu- lates the secretion of saliva. Tea and coffee owe their well-known stimulating action to the presence of the alkaloid caffeine, or trimethyl xanthine. This substance has a diu- retic action upon the kidney and raises blood pressure. This influence upon blood pressure is probably the reason that sleepiness may be prevented by partaking of tea or coffee. Muscular energy is augmented and the sense of fatigue dissipated by nie use of these stimulants. Cocoa, or the chocolate made from it by the addi- tion of sugar, has considerable nutriment due to the presence of proteins, fats, and carbohydrates. Its stimulating action, however, is caused in large measure at least by theobromine or dimethylxanthine. Meat extracts in themselves have very little food value. They contain a trace of protein and gelatin, but the peculiar value of meat extracts lies in the presence of the so-called nitrogenous extractives, namely : creatine, xanthine, hypoxanthine, etc. These substances are likewise stimulants. They also call forth a copious secretion ol gastric juice and for this reason have been called secretogogues. They are undoubtedly of great importance in thi~ respect. The experiments of Folin M would seem to indicate that creatine may serve as a real food-stuff when the diet is deficient in protein. The significance of some hitherto unrecognized com- ponents Of the food is gradually being evolved. An example may be cited in the disease beriberi preva- lent among the Japanese. This condition of abnor- mal nutrition has long been assumed to bear an indefi- nite relation to the large quantity of rice consumed by this nation. < inly recently, however, has it been demonstrated that beriberi is caused presumably by polished rice. Experimentally, it has been shown that a pathological condition of the nature of poly- neuritis may be induced in bints by feeding rice that has been polished and hence deprived of the cortical layers. Both beriberi in man 23 and polyneuritis provoked in birds may be cured by feeding the cortical layers df rice. The chemical nature 21 of the curative substance has not yet been exactly determined for the reason that it is present only in minute amount, probably not more than 0.1 gram per kilo of rice. It is probable that other equally striking relationships bet ween certain at present unappreciated constituents of the food and disorders of nutrition will be made clear as detailed knowledge of the foods is increased. Frank P. Underbill. References. 1 Fischer: Untersuchungen ueber Aminosauren, Polypeptide, und Proteine, 1906. 2 Protein literature may be found as follows: Schryver, The General Characters of the Proteins, 1909: Plimmer, The Chemical Constitution of the Proteins, 190S; Osborne, The Vegetable Proteins, 1909. 3 Compiled from Abderhalden: Text-book of Physiological Chemistry, 190S, and Osborne: The Proteins of the Wheat Kernel, 1907. 4 For literature on carbohydrates consult Armstrong: The Simple Carbohydrates and the Glucosides, 1910. 4a cf. Schwartz: Nutrition Investigations on the Carbohydrates of Lichens, Alga?, and Related Substances: Transactions Con- necticut Academy of Arts and Sciences, 1911, 16, p, 247. 5 Lusk : American Journal of Physiology, 1910-11, p. 27, xxii, 6 Literature relative to fats may be found in Leathes: The Fats, 1910. 7 Long: Text-book of Physiological Chemistry, 1905. 8 Atwater and Bryant : Bulletin 2S (Revised edition) U. S. Dept. of Agriculture. 9 Sherman: Chemistry of Food and Nutrition, 1911, p. 118. 10 cf. Sherman: loc. cit. p. 221, for brief review. 11 Chittenden: Physiological Economy in Nutrition, 1904. Chittenden: The Nutrition of Man, 1907. 11a cf. Mendel: Theorien des Eiweissstoffweehsels nebst einigen praktischen Konsequenzen derselben. Ergebnisse der Physiologie, xi., Jahrgang. 12 Taken from Sherman: loc. cit. 13 Murlin: American Journal of Physiology, 1907, 19, p. 285. 14 Hammarsten: Text-book of Physiological Chemistry, 1911, p. S61 , for literature. 15 Albu and Neuberg: Physiologie und Pathologie des Mineral- stoffn-echsels, 1906. 16 Herter: On Infantilism from Chronic Intestinal Infection, 190S, cf. also Albu and Neuberg, toe. cit. 17 Meltzer: Transactions of Association of American Physicians, 190S. IS Compiled from Sherman, loc. cit. 19 McCollum: Research Bulletin. No. 8 Wisconsin Agricultural Experiment Station and Fingerling: Bichemische Zeitschrift, 1912, 38, p. 448. 20 Quoted from Howell: Text-book of Physiology, 1911. 21 Atwater and Benedict: Bulletin 69, IT. S. Dept. Agriculture; Chittenden, Mendel and Jackson: American Journal of Physology, 1898,1, p. 47; Rosemann : Alcohol in Handbuch der Biochemie, 1911, iv, 1, p, 413. 22 Folin : Hammarsten's Festchrift, 1906. 23 Eykman: Virchow's Archiv., 1S92, 14S, p. 523; Ibid., 1897, 149, p. 187; Archiv. fiir Hygiene, 1906, 58, p. 150. Gryns quoted by Schaumann : Archiv. fiir Schiffs-Tropenhygiene, 1910. Fraser and Stanton: Studies from the Institute for Medical Research. Federated Malay States, No. 12. The Etiology of Beriberi, 1911 24 Funk: Journal of Physiology, 191] , 43, p. 395. 213 Alimentary Tract REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alimentary Tract. — See Digestive Tract. Alimentation, Duodenal. — Every clinician knows how unsatisfactory rectal feeding is. The food is utilized only in a small degree, and, besides, the rectum often becomes irritable, so that the enemata ' must be stopped. It is, therefore, desirable to have some other way of feeding to the exclusion of the stomach. The duodenal pump, 1 which usually serves the pur- pose of obtaining the duodenal contents, can also be used for the introduction of food into the duodenum. This kind of feeding the writer has designated, " duodenal alimentation". 2 , 3 , 4 The method consists simply in introducing the duodenal pump (Fig. 68) into the digestive tract, and feeding is begun as soon as its end is in the duodenum. The apparatus is left in the digestive system for from ten to fourteen days. The thin rubber tube does not inconvenience the patient, and thus every thing is ready for the feeding. This is best done at intervals of two hours. After the feeding, water is forced through the tube, and finally air blown through and t In- stop-cock is closed. We can introduce at one feed- ins; between 240 to 300 c.c. of food slowly. All fluids must, of course, be used at body temperature. The injection of the food is facilitated by the use of a specially constructed support for the duodenal feeding apparatus. (See Fig. 2.) Usually the following nutritive material is used every two hours, from seven in the morning until nine in the evening. Milk, 240 c.c; one raw egg; sugar of milk, fifteen to thirty grams. The mixture is well beaten up, strained, and injected at blood tem- perature. At times I have added cream in order to increase the nutritive value; sometimes have omitted the milk sugar when there was a tendency to loose bowels. In one case, I had to discard the milk en- Fig. 67. — Patient Being Fed through the Duodenum. tirely, since the patient had a marked idiosyncrasy for this substance, even when passed directly into the duodenum. Severe abdominal pains resulted as well as diarrhea. In this case I used the following scheme of nutrition: 7:30 a.m., oatmeal gruel, ISO c.c, one egg, butter, 15 c.c, lactose, 15 c.c; 9.30 a.m., pea soup, 180 c.c, one egg, butter, 15 c.c, lactose, 15 c.c; 11.30 a.m., the same as at 9.30 a.m.; 1 .30 p.m. bouillon, ISO c.c, and one egg; 3.30 p.m., oatmeal gruel, ISO c.c, butter, 15 c.c, one egg, lactose, 15 c.c; 5.30 p.m., pea soup, 180 c.c, butter, 15 c.c, one egg, lactose, 15 c.c; 7.30 p.m., the same as at 5.30 p.m.: 9.30 p.m. bouillon, ISO c.c, and one egg. Total daily quantity oatmeal gruel, 360 c.c; pea soup, 720 c.c; 214 eggs, 8 ; lactose, 90 c.c. ; bouillon, 360 c.c. ; butter, 90 c.c. The pea soup .was made from Knorr's pea flour, one tablespoonful to 250 c.c. of water which was boiled down for from one and a half to two hours to 180 c.c. It is self-evident that many more substances might be utilized for duodenal alimentation. Tin- main point to be observed is that the mixture must be a very fine fluid emulsion, without any coarser particles, so as not to clog the narrow duodenal tube. I; i, therefore best to filter the mixture first through a fine sieve or through gauze. If these rules are observed there will rarely be any difficulty. Fig. 6S. — The Duodenal Feeding Apparatus, with Table Support. A, Tube leading to syringe; B, tube leading to duodenal | C, crank; D, tube leading to fluid; F, fluid; G, glass; T, t; I or shorter support. When crank C is turned parallel to A. fluid can be aspirated from the glass into the syringe. When C is moved parallel to B, the fluid from the syringe can be em] into the duodenum. The patients may be given, besides, a quart of physiological salt solution by rectum, according to the Murphy drop method, or the water may be injected directly into the duodenum, but very slowly, drop by drop. The advantages of duodenal over rectal feeding are at once apparent; for while the rectum and colon are simply organs for the expulsion of feces and for the absorption of possibly remaining liquids, we have to deal in the duodenum with an organ where the most important digestive juices are secreted. In the colon we have to do with the last part of the digestive tract, in the duodenum, however, with the principal part of the digestive apparatus, so that everything is here utilized. Max Eixhorx. References. 1 Medical Record, January 15, 1910. 2 Medical Record, July 16, 1910. 3 Interstate Medical Journal, vol. xvii., No. 10, 1910. 4 Medical Record, March 9, 1910. Alimentation, Rectal. — Rectal alimentation is employed whenever nutrition in the ordinary way (by the mouth) is either impossible or not desirable. I method of alimentation was already used in the Mid- dle Ages and in ancient times. Aetius occasionally mentions such method of feeding. The value of tliis way of nourishing a patient, however, was belii to be very slight, until extensive experimental re- searches with reference to absorption of food from the large bowel had been made. These defini showed that digestion to a great extent can pn" in the colon if the ingested food is suitably prepared. Among the earliest investigators in this direct ion were Hood and Steinhauser. Hood observed that a piece of mutton introduced into the rectum and retail' after some time showed evident signs of digestion. Steinhauser experimented on a patient with a fistula of the ascending colon, and found that pieces of al- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alimentation, Rectal mmen introduced into the fistula could not be disco v- ,v,l in the feces. Pieces of smoked beef and apples, ,,, (fir oilier hand, were found either slightly altered >r entirely unchanged in the stool. Eichhorst stated in l.Si 1 that absorption of album in- ites from the bowel is facilitated, if not made possi- ile, by the addition of common table salt. He ex- lerimented principally with egg albumen mixed with he yolk and with milk. S e years later, Ewald ibserved the very interesting fact thai raw eggs were iiuch better absorbed from the large intestine than artificially peptonized foods (Kemmerich's peptone). Filippi experimented on animals by resecting por- ions of the intestinal canal. He found that after xtirpation of seven-eighths of the small intestine in a there was no appreciable decrease in the absorp- . i of food-; consisting of albuminates and carbohy- -. while nineteen per cent, of the ingested fat eturned with the feces. This clearly shows that the ilon can vicariously do the work of the small intestine. [I further demonstrates that albuminates can be ab- ied from the large intestine and enter the lacteals ..ithoiit previous peptonization. These remarkable meats have been confirmed by Aldor. This er experimented principally with milk, and il «i I t he coagulat ion of t he milk in the large bowel action of bacteria, not to enzymes. He found after the injection of from ten to fifteen ounces of uilk into the bowel, intestinal lavage, performed to one and a half hours later, showed only minute particles of milk. The spontaneous evacuation re- ulting thereafter likewise contained but very small it tions of coagulated milk. Aldor, in his paper, arrived at the following conclusions: 1. A quart of milk, injected by means of a fountain syringe into the bowel, produces no pains either luring the injection or afterward. No irritation of the intestine follows, and milk is most suitable for a nutritive enema. 2. The coagulation of the milk, which is due to the action of the bacterium coli commune, is rather detri- mental to absorption. This coagulation can be pre- vented, (a) by thorough lavage of the bowel before giving the nutritive enema, (b) by adding 1 to 1.5 grams (gr. xvi.-xxiv.) of sodium carbonate to one quart of milk. 3. No digestion takes place in the large bowel. 4. Carbohydrates are absorbed in an excellent manner, albuminates in a great measure, and fats but poorly. 5. After an injection of a quart of milk into the bowel, there was never found either albumin or sugar in the urine. In America the attention of the medical profession was first directed to rectal alimentation by Austin Flint, who read an extensive and important paper on this subject before the New York Academy of Medi- cine in December, 1877. Flint mentioned a case in which a woman was almost wholly nourished per ■turn for five years. After emphasizing the impor- tance of rectal alimentation in instances in which the usual mode of nutrition fails or is impossible, he gave directions as to the mode of employment of the nutri- tive^ enemata. From three to six ounces of fluid or semi-fluid foods may be injected at intervals of from three to six hours. He did not deem it neces- sary to wash out the rectum prior to each administra- tion of the nutritive enema. Flint, as well as Peasley, lordyce Barker, A. H. Smith, and G. M. Smith, who took part in the discussion of the above paper, had all practised this method of feeding with best results. A. H. Smith mentioned several instances of gastric ulcer in which nutrition had been successfully maintained by rectal alimentation for from eleven to sixteen and twenty-one days. He was the first who suggested the use of defibrinated blood for this purpose. Very shortly afterward W. Bodenhamer published an instructive monograph on rectal medication, in which he also laid stress upon t l t e practical value of rectal alimentation as deserving much more frequent application than heretofore. Stillman, in his paper on rectal alimentation, says: "The clinical fact remains th.it certain foods, digested or undigested, are taken into the system when thrown into the rectum; that the power of absorption there may be good when the stomach is weak and rebellious; that it is assimilated, for the body gains in flesh and power, and that there may be merely the customary evacuation as an excretory resultant. As far as 1 am aware, no danger attends feeding by the rectum, when conducted with ordinary care and intelligence on the part of nurses or attendants." In this paper Stillman calls attention to the use of supplementary rectal feeding, i.e. to the use of nutrient enemata while the stomach is yet performing its functions to quite a considerable extent, as, for instance, in chronic gastritis, gastralgia, nausea, etc. He used principally enemata of milk according to the following formula: five grains of pancreatic extract and fifteen grains of bicarbonate of sodium to a pint of milk. The writer has had extensive experience with rectal alimentation and is fully convinced of its great prac- tical value, notwithstanding the impossibility of keeping thereby the body weight in balance. The indications for this mode of alimentation may be summarized as follows: 1. In conditions in which the passage of food from the mouth to the stomach or to the small intestine is impeded or made impossible (strictures, benign or malignant, of a high degree, of the esophagus or cardia, spasmodic or paralytic conditions of the esophagus, pyloric or duodenal stenosis). 2. In ulcer of the stomach accompanied by consider- able hemorrhage, or when the usual methods of treatment have failed. 3. Incessant vomiting, no matter to what cause it be due. 4. In all conditions in which absolute rest for the stomach seems to be imperative (intense pains soon after ingestion of food; persistent hyperchlorhydria of a high degree; intense chronic continuous gastro- succorrhea; pronounced ischochymia). 5. In typhoid fever and other severe lesions of the small intestine necessitating a complete rest of this portion of the bowel. For how long a period rectal alimentation should be administered depends upon the condition necessitat- ing it. In ulcers and irritating affections of the stomach, rectal alimentation should be administered alone, without any additional nourishment through the mouth, for a period varying from one to two weeks, when the natural mode of nutrition may be cautiously resumed. In cases in which there is an organic obstacle within the esophagus or at the pylorus preventing the passage of food into the intestine, rectal feeding must be carried on as long as the impediment exists (in operative cases until a few days after the operation has been performed; in inoperable cases, indefinitely). Here, whenever possible, besides the enemata, small quantities of liquid foods may also be given by way of the mouth. Shortly after operations on the esophagus, stomach, and small intestine, rectal alimentation must be administered for a period varying from four days to a week or ten days. Mode of Administration. — Before administering the feeding enema, a cleansing injection (consisting of a quart of water and a teaspoonful of salt) should be given early in the morning, in order thoroughly to evacuate the bowel. One hour later the first rectal alimentation may be administered. The feeding enema is best injected by means of a fountain syringe or a Davidson syringe, or a plain hard-rubber piston syringe, and a soft-rubber rectal tube, which is intro- 215 Alimentation, Rectal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES duced into the anus for a distance of about five to seven inches. The injection should be administered slowly and without much force. After the with- drawal of the tube from the rectum, the patient is told to lie quietly and to endeavor to retain the enema. The quantity of the feeding enema may be from five to ten ounces. From three to five such enemata may be given daily. The following substances may be used as feeding enemata: (a) The different kinds of peptones and propeptones in the market (Rudisch's or Kemmerich's peptone, somatose, sanose, sanatogen), of which about one to two ounces dissolved in from six to eight ounces of water are to be injected. The different beef juices i Valen- tine's beef juice, bovinine, Mosquera's beef jelly, etc.) may also.be dissolved in water and injected in corre- sponding quantities. (6) The milk and egg enemata; these are the most commonly used. Their composition is as follows: six to seven ounces of milk, one or two raw eggs well beaten up in it, one teaspoonful of powdered sugar, and one-third of a teaspoonful of common table salt. Pancreatin (one tube of Fairchild's pancreatin) may be added to such an enema, to facilitate its assimilation. (c) Meat pancreas enema. Leube employs ene- mata consisting of well-chopped meat (five ounces), fresh pancreas (two ounces), one ounce of fat (butter) — all these ingredients being thoroughly mixed with about six ounces of water. (d) Grape sugar enema. One ounce of grape sugar in ten ounces of water or physiological saline solution. Instead of always using one and the same nourish- ing enema, the above combinations may be alternately administered. In conjunction with these food enemata, injections of water into the bowel are made in order to increase the amount of fluid in the system. These injections of water for absorption are of great importance. They are retained much better if injected very slowly by the so-called "Murphy Drop Method." Usually saline solutions are employed, in quantities varying from a pint to a quart, which may be given twice a day. Max Einhorn. Alkalies, Antacids. — (See also under title of each drug.) Medicines which are administered for the purpose of correcting acidity. The terms are almost synonymous, but it will be found that the drugs arrange themselves into two groups, according ot their solubility, which in a great measure determines their therapeutic uses. In one we have potash, soda, and lithia; in the other lime, magnesia, cerium. The former are generally employed as alkalies, the latter as antacids. Ammonia is intermediate; its character would place it in the first group, but its therapeutic use makes it belong rather to the second. Alkalies are all powerful depressors. Potash and lithia are the most injurious, and soda is the least. They reduce the blood corpuscles and the proto- plasmic tissue. In large doses they are cardiac poi- sons, and their prolonged use in moderate doses causes anemia, loss of body weight, and loss of mus- cular power. Potash, soda, and lithia salts are very soluble, and are readily absorbed and as readily excreted; they pass from the system in a very short time. They are normal constituents of the blood, and their presence in increased amount tends to render the plasma more alkaline. Those of the second group, comprising lime, mag- nesia, and cerium, are much less soluble, and even their more soluble salts (as the sulphate of magnesium, etc.) are but slowly absorbed. In consequence their action is almost entirely limited to the digestive tract. Many of their soluble salts, as the chlorides, phos- phates, and hypophosphites, are only mildly alka- line, and are of value more for the acids in combina- tion than for the alkaline base. The action of alkalies upon the secretions of the stomach, as formulated by Ringer, has been confirmed by subsequent experience. His view is that the con- tact of weak alkaline solutions with glands secreting an alkaline fluid causes a lessening of the secretion while on acid-secreting glands the effect is to cause an increase of the acid secretion. Advantage has been taken of this in gastric disturbances, when there is a deficiency of acid during digestion. The admin- istration of alkalies just before meals has proved most serviceable in relieving this defect. They rnusl be given well diluted and in moderate doses. The bi- carbonate of sodium or the bicarbonate of potassium is generally selected; it is to be given in five-grain doses. Ammonia, in the form of the aromatic spirits, is often combined with some stomachic, as tincture of rhubarb, tincture of cardamom, capsicum, gin- ger, or peppermint, and in addition a vegetable bitter. This combination has been found to be valuable. In addition to the local effect thus produced upon gastric digestion, a further benefit is derived by the action of alkalies after absorption. They rapidly pass into and improve the blood, and during excretion they cause a general stimulation of all secreting organs. As alkalizers of the blood, they are used in gouty and rheumatic conditions, in lithiasis, and in many dis- orders of the skin in which there is supposed to be an excess of uric acid or allied acids in the blood. Their purpose is to keep these morbid products in solution until they are carried out of the system. The potas- sium salts are preferred, as their rapid absorption renders the blood more quickly alkaline, while their equally rapid excretion prevents any accumulation. For immediate action the bicarbonate salt is selected; but when a prolonged use is required, the citrate, acetate, or tartrate is preferred. Sodium salts are more slowly absorbed and are less powerful alkalies. The normal alkaline state of the blood is due chiefly to sodium salts, and as they are less depressing than potassium salts, they offer many advantages when a prolonged course of treatment is necessary. In treating rheumatism with the alkalies, they require to be given freely until the urine becomes alkaline, and then they should be reduced, enough being given simply to maintain this reaction. There may be given a dram and a half of bicarbonate of sodium and half a dram of the acetate of potassium every three or four hours, well diluted, for four or five doses; fol- lowing this, fifteen or twenty grains will usually be sufficient. Lithia is very similar to potash in the rapidity of its absorption and excretion. The alkalies are excreted rapidly by all the secreting organs. Their effect is most evident on the kidneys, and during excretion they render the urine alkaline. At the same time they augment the watery flow through an increased activity of the renal cells. The secretion of all organs is increased, as is also the se- cretion of the mucous surfaces. The alkalies are also of benefit when applied to the surface of the body. In rheumatism a hot lotion of carbonate of sodium with opium often affords relief to the painful joint. In all forms of cutaneous disease accompanied by a troublesome itching, an alkaline wash of carbonate of sodium or potassium, half a dram to the pint, is of service, and in eczema during the early stage, with an alkaline watery discharge, the same solution is curative. Burns and scalds may be treated in the same way, the solution being con- stantly applied. The alkali removes the heat and pain and allays inflammatory action. The bites and stings of insects and the urticaria produced by poisonous plants are also benefited. The oxides and carbonates of calcium and magne- sium are the most serviceable salts as antacids, on ac- count of their insolubility. If these drugs are given 216 K INFERENCE HANDHOOK OF THE MEDICAL SCIENCES Allantois n small quantities their action maybe Limited to the tomach; when they are freely administered, their ction is continued into the intestines. They neu- ralize all acids with which they come in contact, and iv contact with the mucous surface they exercise a oothing and sedative effect. In addition to neu- ralizing the local acids, they arc of value as antidote i ,, poisoning by acids, and also in poisoning by vege- t ble poisons, the alkali precipitating the poisonous Jkaloids and retarding their absorption. In the ie the antacid action is continued, but the iltimate effects of lime and magnesia differ; the for- ts as a mild astringent, while the latter be- omes converted into the bicarbonate and acts as a axative. The soluble alkalies are not so useful as antacids, oid are of lit i Ie service when an effect in the intest ines required. Sodium bicarbonate, however, is a well- cnown antacid. Its disadvantages are that it tends o generate a large amount of carbonic acid gas, is stimulating instead of soothing to the mucous •urface. The aromatic spirit of ammonia is simi- ar in its action and more rapid. Cerium oxalate ind bismuth are both useful antacids, their chief value being due to the local soothing action which I hey exert upon the mucous membrane. The ce- rium salt has probably a sedative action on the ter- minals of the nerves. Beaumont Small. Alkaloids. — See Active Constituents of Plants. Alkanet. — Orcannettc. The fleshy root of Alhanna ."■in (L.) Tausch. (fam. Boraginacem), a small perennial herb of Europe and Asia Minor, largely illltivated for its coloring matter. The dried root, a foot or more in length and about a half inch in thickness, its bark purple-red without, deep red within, its wood pinkish-white, is sometimes marketed entire, but more frequently as a stringy, shredded, tough mass. Its only value is for coloring purposes, the coloring matter being alkannin or alkanna red. Alkannin is a dark, brownish-red, resinous mass, insoluble in water, but soluble in alcohol and ether. Acids intensify the red color, alkalies convert it to a bluish-green, in which respect it acts like hematoxylin. H. H. RusBY. Alkaptonuria. — See Alcaptonuria. Allantiasis. — See Food Poisoning. Allantoin. — This is a colorless crystalline substance, glyoxyl diureide, C 1 H ll N 1 3 , very slightly soluble in cold water and cold alcohol, but readily soluble in boiling water and warm alcohol. It may be obtained by the alkaline oxidation of uric acid in the cold. In some of the mammalia, in which it occurs in the urine, it is probably an end-product of metabolism, but is not so in man, the minute quantities some- times found in healthy human urine being derived from the food and excreted unchanged by the kidneys. It is found in the allantoic fluid (whence the name), in the amniotic fluid, in the urine of the new-born and of pregnant women, in the urine of the dog, cat, and certain other mammals, usually in minute quantity in the urine of healthy persons, and in milk. It is also found in the growing parts (buds, the bark of twigs, etc.) of various plants, and especially in the root of comfrey, Symphytum officinale. Macalister 1 of Liverpool, investigating the healing, or cell-proliferating, properties of this plant, a popular vulnerary in domestic practice, found that they were due to the presence of a crystalline substance, identical in its empirical formula and chemical reactions with allantoin. A number of experiments in the way of the application of this substance to old ulcers, fistulre, and other sores, made by Macalister, BramwelF, and others 3 seemed to show that it is a cell-proliferant of < siderable power. Ulcers which had long resisted treatment healed readily when treated with allantoin or with an extract of the root of comfrey. Sinuses of long standing also closed promptly after the insertion of wicks of gauze impregnated with a solution of allantoin. T I,. S. References. 1 . Macalister, Charles J Liverpool Medico-ChirurgicalJoumal, January, 1912; British Medical Journal, January 6, 1912. 2. Bramwell, William: British Medical Journal, January6, L912 3. Murray, R. W.: British Medical Journal, January 13, 1912. Allantois. — (From N. T.., allantoides; Creek, dXXSs (dXXovr-), a sausage, and (l~io$. form: sausage-shaped The allantois is one of the fetal membranes peculiar to I he group of higher vetebrates in which the embryo is enveloped in an amnion, the Amninta. These are reptiles, birds, and mammals. The reptiles and birds are often grouped together on account of certain anatomical similarities under the name, Sauropsida. am Fig. 69. — Median Longitudinal Section through a Chick Embryo at the End of the Third Day of Incubation. X20. all, Allantois; am, amnion; ho, hind gut; n, neural canal; rv, right ventricle of the heart; up, splanchnopleure; t, tail. (After Marshall. There is no allantois in the fishes and Amphibia, but the Amphibia have a highly vascular urinary bladder that is usually regarded as homologous with the allantois. In the Amniota the embryo is formed from a com- paratively small part of the blastoderm (see Area Embryonalis). At an early stage of development the mesoderm becomes divided into two layers of cells, with a cavity between known as the caelom, a part of which becomes the body cavity. The outer layer unites with the ectoderm to form the somato- pleure, which gives rise to the body wall, the amnion (see Amnion) and the chorion; while the inner layer unites with the endoderm, or hypoblast, to form the splanchnopleure, which gives rise to the wall of the digestive tract and its appendages and to the wall of the yolk-sac (see Fetus). The allantois is a diverticulum of the posterior end of the embryonic digestive tract and is composed 217 Allantois REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of two layers of cells, endoderm and splanchnic meso- derm. It grows out usually as a thin-walled sac between the amnion and the yolk-sac, and blood- vessels develop in its mesodermal tissue. In most placental mammals the distal portion of the allantois fuses with the chorion and forms the essential part of the fetal portion of the placenta (see Placenta), while the proximal part becomes dilated to form the urinary bladder, and a part of the middle portion finally loses its lumen and persists as the urachus, connecting the bladder with the umbilicus. In regard to the details of its origin, its structure, and its relations to adjacent parts, the allantois varies greatly in different groups of animals. Fig. 70. — Diagram of Fetal -Membranes in a Hen's Egg. .1, Remnant of the albumen: All, allantois; Am, amnion; C, chorion; S, shell membrane; Y, yolk. (After H. Virchow, from Strahl.) With respect to the allantois the Amniota may be divided into two groups, first, those with a free allantois, including the Sauropsida, the Monotremes, the Marsupials, and most of the placental mammals, such as the Insectivora, the Ungulates, the Lemurs, etc.; second, those in which the allantois is more or less enclosed in a connective stalk by which the em- bryo is attached to the chorion from a very early period in its development. This group includes some Rodents, Tarsius, the Monkeys, and Man. We may take the common hen as a type of the Sauropsida. At about the thirty-sixth hour of incubation the rudiment of the allantois first appears as a shallow pocket in the endoderm, at the extreme posterior end of the embryo. As the formation of the tail fold progresses, this comes to lie on the ven- tral side of the hind gut (Fig. 69). By the end of the fifth day it has grown out into the ccelomic space (exoccelom) between the yolk-sac and the amnion, as a vesicle of considerable size. It then grows rapidly until, uniting with the chorion, it spreads out as a large, thin-walled, highly vascular sac, and com- pletely surrounds the amnion and yolk-sac. It serves as the organ of respiration for the embryo. Finally a part of it nearly surrounds the remnant of the albumen and probably assists in its absorption (Fig. 70). A short time before hatching, its vessels are cut off by the closure of the umbilicus, it dries up, and is left behind when the chick emerges from the shell. The allantois has essentially the same history in most reptiles. In a lizard (Lacerta), according to Strahl, confirmed by Corning and Janosik, it arises in a peculiar way independently of the gut and comes into connection with it secondarily. And Giacomini found that in another lizard, which brings forth its young alive, Seps chalcidt ■*, it probably has a nutri- tive as well as a respiratory function. In this species both the allantois and the yolk-sac fuse with the chorion, forming an allanto-chorion and an omphalo- chorion. The egg is very small, without envelopes, and the allanto-chorion becomes folded into a series of ridges and hollows which fit into corresponding inequalities in the wall of the viaduct, forming a kind of placenta. A similar but less perfect connection is formed by the omphalo-chorion. In the most primitive of living mammals, the Monotremes, which lay eggs, the relation of the' fetal membranes is essentially similar to what obtains in the Sauropsida. The Marsupials are born in a very imperfect con- pit ion and a true placenta is rarely formed (Hill, 1897), In this group the allantois remains comparatively small, and in the opossum, according to Selenka, it does not even touch the chorion; and it begins to degenerate before birth. The yolk-sac, on the other hand, is large, filling most of the space between the embryo and the chorion. It fuses with the latter, I e- comes highly vascular, and serves during fetal life both as an organ of nutrition and as one of respiration. These conditions are usually regarded as primitive; for the Marsupials are generally supposed to have been derived from monotreme ancestors and to have given rise in turn to the placental mammals. Among the mammals with a free allantois the most diagrammatic arrangement is to be found in the mole, one of the Insectivora, a group that shi many primitive characters. According to Strahl, in a cross-section of a gravid uterus of the mole, Talpa i uropea (Fig. 71), one may see the embryo surrounded by the amnion, except on the ventral side, where the yolk-sac and the allantois are attached. The allantois has a large lumen, which occupies the greater part of the space between the embryo and the chorion. Its outer wall fuses with the chorion, and the greater part of it gives rise to the thickened placenta. On the opposite side the smaller yolk-sac spreads out in a similar way and likewise fuses with the chorion, but its outer surface does not become vascular like that of the allantois. Except for the increase in the size of the embryo and the correspond- ing reduction in the lumina of the allantois and yolk- sac, these relations persist until the end of gestation. We may take the sheep as representing the type of allantois common to the Ungulates. Fig. 71. — Fetal Membranes of the Mole e. Embryo; am. amnion; all, allantois; p, placenta; y, yolk-sac. (After Strahl.) According to Bonnet, the rudiment of the allantois appears in the sheep at about the end of the fifteenth day after copulation. The tail fold has not yet formed, and the allantois appears as a sac-like pos- terior prolongation in the axis of the gut, which is then being folded off from the general endoderm. With the development of the tail fold the allantoic stalk gradually assumes its normal position as an appen- dage of the hind gut. Very soon the young allantois begins to spread laterally, so that by the end of the sixteenth day it has become a half-moon-shaped appendage nearly half as large as the embryo. From •J IS REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Allanlol-, 72. — Diagrams Showing the Developmenl of the Fetal Membranes of the Sheep. e ec i "ii the twelfth day after copulation; />', thirteenth -lay; C, about e; I), longitudinal section about the same age; K, transverse section of an mbryo; F, diagram of the fetal membranes at the end of the first month; 'ill, ; nil ch, allanto-chorion; ach, amniogen chorion; am, amnion; ams, amnion stalk; ro, cotyledon; eel, ectoderm; end, entoderm; ?;, cavity of yolk-sac. (After persistent lumem Bonnet.) this time on, its growth is rapid until it extends the whole length of the chorion. As it becomes dis- tended with liquid its mesodermal layer is pressed closely against that of the chorion, and the two fuse and form the important placental structures. At the twenty-first day, when the embryo is about a third of an inch in length, the allantois is a large sausage- shaped bag measuring more than a fool from tip in tip. The embryo en- veloped in its relatively small amnion lii is in a depression .-it the center of the allantois, ami the yolk-sac has dwin- dled to a hollow, thread-like structure lying in a groove in one side of the allantois and extending in both direc- tions lo 1 1 10 ends of the chorion (fig. 72, /•'). The Carnivora have likewise an allantois with a large lumen. The allantois tit first bends dorsally and enlarges into a mushroom-shaped sac. lis outer wall unites with the chorion and forms at first a discoidal placenta. But the allantois continues to enlarge until it has fused with the whole im i r surface of the chorion. Ii completely surrounds the amnion, containing the embryo, and finally encloses also the yolk-sac. \l lie' time lime (lie |i!:i- centa extends around the equator of the egg as a broad band, and finally acquires its characl erisl ic zonary form. In (he Rodentia (he allantois unites with only a pari of the chorion mi (he dor ,il side of (he embryo, the res) of (In- chorion being fused with the large cup-shaped yolk-sac, Keibel (1906). In this group there are two types of allantois. One of these is represented by the rabbit (Fig. 73), and has a large In the other type, am coel Fro. 73. — Transverse Section through the Gravid Uterus of a Rabbit at the End of the Nineteenth Hay of Gestation. X 1 3/4. fi'\ Allantoic artery; all, allantois; am, amnion; cod, exoccelom; nun. mesometrium; p, placenta; y, cavity of yolk-sac, which is continuous with the uterine cavity owing to the absorption of the lew er wall of the yolk sac represented by the dotted line yl. (After Marshall.) represented by the rat and the guinea- pig, the lumen is very small or may disappear altogether. According to Fleischmann, the squirrel presents a form of allantois intermediate be- tween these two types. Aside from these differences in the allantois, the rodents are generally alike in having a large omphalo-chorion, a smaller discoidal placenta, a small amnion, and a large ccelomic cavity filled with fluid, separating the allantois from the yolk-sac (Fig. 73). The second type of allantois is found in the Pri- mates; that is Tarsius, the monkeys, and man. In Fig. 74. — Diagram of a Blastocyst of Tarsius in Sagittal Section. all, Allantois; am, Amnion; va, and ha, anterior and posterior amniotic folds; c, exoccelom; n, yolk-sac; nc, neurenteric canal; j>, placenta. (From Hubrecht.) the earliest known embryos of both the monkeys and man the fetal membranes are already more or less established, and the earliest stages of their develop- ment are therefore unknown. But there is no reason to doubt that Hubrecht (1908) is correct in his inference that the earlier stages in the higher Primates are similar to what he found in an extraor- 219 Allantois REFERENCE HANDBOOK OF THE MEDICAL SCIENCES dinarily complete series of embryos of Tarsius. This interesting animal is a small arboreal mammal found in the forests of Borneo, Sumatra, Java, Banka and the Philippine Islands. It is usually classified with the Lemurs. But while all true Lemurs that have been examined exhibit a free allantois, Tarsius closely resembles the true Primates in the corre- sponding stages of development (Fig. 7-1). Emb Am Fig. 75. — Embryo of the gibbon, Hylobales concolor. All, Allantois; am. amnion; b.s.. connective stalk; emb, embryonic shield; veu, neurenteric canal; yk, yolk-sac; Ye, blood-vessels. (After Selenka from Minot.) In Tarsius the embryonic shield (area embryo- nalis) is developed on the surface of the blastocyst, and is subsequently covered by the folds of the amnion The development of the allantois begins by a proliferation of mesodermal cells which extends backward from the primitive streak, and forms a ridge on the inner side of the somatopleure. This ridge is the " connective stalk," which is continuous from the first with the chorion. At the point in the median line where the somatic and splanchnic mesodermal layers join, a tubular projection of the endoderm grows into the connective stalk from the yolk-sac and forms the lumen of the ^fl&las Fig. ,6— Human Embryo "von HerfT." Internal Diameter of Blastocysts about 4 mm. Side view after removal of part of chorion a. Amnion; 6, blood-islands (much more prominent in original); c, chorion; «, connective stalk; ec, ectoderm of chorion- HaudbuchT 1 "' * y0lt " SaC - (AftCT SpCe fr ° m Hert »'^ allantois. Even before the appearance of the area vasculosa in the yolk-sac, there begin to develop in the connective stalk blood-vessels that are destined lSQoT" P lacental circulatory system (Hubrecht, When Tarsius has reached this stage, it corresponds to the youngest embryo of the gibbon, Hylobates, 220 described by Selenka (1900, Figs. 75), and to the youngest human embryo described by Count von Spree, the von Herff embryo (Keibel, 1906 FiVs - ■ and 86). The gibbon and man appear to dim', however from Tarsius in that the blood-vessels develop first in the area vasculosa of the yolk sai i ■?' /. 7 -"- Human Embryo, same as Fie. 76. Diagram of « longitudinal section. „, Amnion; all, allantois; c, chorion r, connective stalk; e, area embryonalis; ec, ectoderm of chorion- „",' mesoderm; y, yolk-sac. (After Spee, from Hertwig's Handbuch.) and subsequently grow out into the connective stalk and thence into the chorion to form the fetal vessels of the placenta. In a human embryo 2.15 mm. in length (Fig. 78) the allantois is a long narrow tube extending from the hind gut into the connective stalk parallel with the allantoic vessels as far as the chorion, where it ends blindly. By the continued infolding of the somatopleure the body wall is completed except at the umbilicus where the extraembryonic part of the somatopleure forms a tube enclosing the stalk of the yolk-sac and exclusive 8 -T"™^. Em bryo "Gle." Dimensions of blastocyst, TsA i m P ' 8 : 5 X 10X6.5 mm. ; length of area embryo amnion ;>, r ?° d Si IP t,al SeCtim - - 4 "' Allantois; „„,. amnion, 6. s ., connective stalk; cho, chorion; ec, ectoderm' . „l from&r- mesoderm: *■ vUU: vk - yoi - sac - (A,ur the connective stalk with their vessels; the whole being he umbilical cord, of which the connective stalk m the center. According to Lowy (Grosser, 1910) the allantois remains hollow throughout its entire length m human embryos of S mm. maximum length. In older embryos its lumen soon begins to be obliter- ated at the distal end, but even in the fourth month ki:i i:ki:\( k handbook of the medical sciences Alleghany Springs remains of the duct lined by cubical epithelium may be found in the cord near the embryo. The allantoic fluid of the cow lias been shown by Doderlein to differ from the amniotic fluid in being rer in salts of sodium and richer in nitrogen. The latter increases with the age of the fetus, indicating that it is an excretory product; and according to Foster and Balfour urates are abundant in the allan- toic fluid of the chick by the sixteenth day. The circulation in the allantois takes place pri- marily through two pairs of blood-vessels, the allan- toic or umbilical arteries, and the allantoic veins :,| their branches. The allantoic arteries arise as lireel prolongations of the primitive forks of the iorta. When the hind limbs bud out, the external iliac arteries arise as branches of the allantoic arteries. In the chick the right allantoic artery does not grow so fast as the left, and it finally dwin- dles and disap- pears altogether. In man the two arteries persist. They may be traced from the posterior end of the aorta through the umbilical cord (see U m bil i c a I Cord) to the pla- centa, where they branch freely. The two allan- toic veins in the chick are formed during the fourth day. They unite in the body of the embryo, becoming there a single allan- toic vein, which passes forward on the left side and joins the left vitel- line vein. In man and other mam- mals the two allan- toic veins at first open into the sinus venosus, one on each side, in com- pany with the corresponding Cuvierian and vitelline veins. Later, while the allantoic veins remain dis- tinct within the embryo, in the allantoic stalk they fuse to form a single vessel. During the fourth week in man the allantoic veins become separated from the duus venosus. The smaller, right one soon after dis- ears, while the left one unites with the portal vein (formed by the union of the vitelline veins) and increases in size. Creighton has described (1S99) a series of lym- phatic cylinders and capsules surrounding certain allantoic vessels in the chick. They are found upon the vessels where the allantois and amnion come into contact, and are supposed to aid in the absorp- tion of the yolk and albumen. (For a description of the circulation in the placental portion of the allantois, see Placenta.) The principal adult structure developed from the allantois is the urinary bladder. Of that part of the allantois which lies within the body of the embryo, the proximal portion begins to enlarge during the second month to form the bladder, while the tapering distal portion finally loses its lumen and becomes the urachus, or ligamentum vesica? medium, connecting the bladder with the umbilicus. The portions of the allantoic arteries within the embryo are called the hypogastric arteries, and are more or less homol- Ftc. 79. — Human Embryo of 2.15 mm., Reconstructed from Sections. All, Allan- is; Ao, aorta; Ht, endothelial heart; /. , liver; Om, omphalo-mesenteric vein; b . allantoic vein; IV:, yolk-sac. (From Minot, after His.) OgOUS with arteries of the same name in lower verte- brates. At birth the dislal part of the hypogastric on each side loses its I -n and become- a -olid cord enclosed in the superior ligament of the bladder, while the proximal part persists as the common iliac, internal iliac ia^ far as the bifurcation), and superior vesical arteries. The remaining allantoic or um- bilical vein loses its cavity at birth and becomes the ligamentum teres, or round ligament, connecting the liver with the umbilicus I see Ft Ins). Robert Payne Bigelow. References. Bonnet, R.: 18S3. Ueber die Bih&ute der Wiederkiiuer. Sits.- Ber. Morph. Phys., Mum-hen, Bd. ii. Creighton: 1S99. A system of perivascular cylinders and cap- sules in the united amnion-allantois of the chick. Jour. Anat. Phys. Vol xxxiii p, ">_'7 545. Grosser, O.: 1910. Development of the egg membranes and the placenta. Keibel and Mall's Manual of Human Kmbrvologv, p 91-179. Herzog, M.: 1909. Contribution to our knowledge of the earliest known stages of placentation and embryonic development in man. Amer. Jour. Anat. Vol 9 p. 361— tOO. Hill, J. P.: 1S97. The Placentation of Perameles. Q. J. Mic. Sci., vol. xl. Hubrecht, A. A. W.: 1896. Hie Keimblase von Tarsius. Festschrift fur Gegenbaur, Kd. ii., p. 147-17S, Hubrecht, A. A. W.: 1897. Descent of the Primates, New York, Scribner's. Hubrecht, A. A. W.: 1902. Furchung und Keimblattbildung bei Tarsius Spectrum. Verh. K. Akad. v. Weten. Amsterdam, Sect. 2, vol. viii.. No. 6. Hubrecht, A. A. \\\: 1908. Early Ontogenetic Phenomena in Mammals and their bearing on our Interpretation of the Phylo- geny of the Vertebrates. Quart. Jour. Mic. Sci., vol. liii., p. 1-181. Hubrecht, A. A. W.: 1912. Feetal Membranes of the Verte- brates Proc. Seventh Internat. Zodl. Cong., 1907, 426. Keibel, F. : 1902. Die Entwiehelung der ausseren Korperform der Werbeltierembryonen. Hertweg's Handbuch, Bd. i., Teil 2, 1-176. Minot, C. S-: 1903. Laboratory Text-book of Embryology. Phila., Blakiston. Schauinsland, H.: 1902. Die Entwickelung der Eihiiute der Reptilien und der Vogel. Hertwig's Handbuch, Bd. i., Teil 2, p. 177-334. Selenka, E.: 1900. Studien iiber Entwickelungsgeschichte der Tiere, Heft 7 and 8, Entwickelung des Gibbon. Wiesbaden; Kreidel. Spee, F. Graf von: 1S96. Ueber friihe Entwickelungsstufen des mensehlichen Eies. Arch. f. Anat., p. 1-30. StrahL H.: 1891. Eihiiute und Placenta des Sauropsiden. Ergeb. Anat. u. Entwick. , Bd. i. Strahl, H.: 1902. Die Embryonalhullen der Sauger und die Placenta. Hertwig's Handbuch, Bd. i., Teil 2, p. 23.3-270. Alleghany Springs. — Montgomery County, Virginia. Post-office. — Allegheny Springs. Access. — Ma Norfolk and Western Railroad to Shawsville station, thence by carriage or omnibus three and a half miles to springs. Hotel and cottages. This well-known resort is located on the eastern slope of the Alleghanies, on the head waters of the Roanoke River. The hotel and principal range of cottages occupy smooth and undulating hills, gently sloping to a broad, grass-covered lawn of forty acres, extending to the banks of the river. The accommoda- tions here are first class, affording every convenience and comfort to the pleasure seeker as well as to the invalid. The hotel is large and spacious, and is supplied with all requisite improvements. Contigu- ous to the hotel are 150 double cabins, arranged with a view to the comfort and good health of the guests. The scenery in the vicinity is not excelled for pictur- esque loveliness and variety at any watering place in the Old Dominion. Only one spring, which flows about thirty gallons per hour, is in use at the present time. The water is limpid, and has a temperature of 56° F. The following is the latest analysis of this water: 221 Alleghany Springs REFERENCE HANDBOOK OF THE MEDICAL SCIENCES One Gallon, 70.000 Chains, Contains: Grains, Magnesium sulphate 50 . S8 Calcium sulphate llo.29 Sodium sulphate 1.72 Potassium sulphate 3.70 Copper carbonate trace. Lead carbonate trace. Zinc carbonate trace. Iron carbonate 0. 16 Manganese carbonate 0.06 Calcium carbonate 3 .61 Magnesium carbonate 0.36 S1 fntium carbonate 0.06 Barium carbonate . 02 Lithium carbonate trace. Magnesium nitrate 3 . 22 Ammonium nitrate O.o6 Aluminum phosphate 0.03 Aluminum silicate . 20 Calcium fluoride - • - - ■ . 02 Sodium chloride 0.2Ti Silicic acid °- 8 8 Crenic acid trace. Aprocrenic acid trace. Other organic matter trace. Cobalt carbonate trace. Antimony teroxide trace. 182.95 Solid ingredients by direct evaporation gave 184.07 Half combined carbonic acid 1.89 Free carbonic acid* o 46 Hydrosulphuric aeidf trace. Total amount of ingredients 191 -42 This water is distinguished for the great variety of its mineral constituents. When taken in large doses it is actively diuretic and cathartic, operating with special activity on the mucous membrane of the lower intestines. In smaller doses its action may be de- scribed as tonic, alterative, and detergent. The water has been found particularly beneficial in the treatment of dyspepsia, for which it has a wide repu- tation. Excellent effects are also observed in nervous affections, in diseases of the liver and kidneys, in catarrh of the stomach and intestines, diarrhea, and dysentery, gout, rheumatism and troubles arising from a faulty venous circulation, such as headache, dizziness, and hemorrhoids. It is recommended in small doses by many physicians in the treatment of anemia and chlorosis, general debility, and other con- ditions in which tonic and reconstructive effects are sought. The water is used commercially. Emma E. Walker. * S. 455726 grains of carbonic acid is equal to 11.544067 cubic inches. t 0.000139 grain of hydrosulphuric acid is equal to 0.000369 cubic inches. Allen, Harrison A. — Born in Philadelphia, Pa., on April 17, 1841. He received the degree of Doctor of Medicine in 1861, and held the position of Resident Physician in the Pennsylvania Hospital up to 1862, when he entered the Confederate Army. Upon his return to Philadelphia in 1865 he was appointed Instructor in Comparative Anatomy and Medical Zoology in the University of Pennsylvania. In 186i he was made Professor of Anatomy and Surgery in the Philadelphia Dental College, and in 1870 he was appointed a Surgeon in the Philadelphia Hospital. From 1875 to 1885 he held the Chair of Physiology in the University of Pennsylvania, and in 1S94 he became the first Director of the newly founded Wistar Institute of Anatomy. His death occurred in November, 1S97. Allen acquired considerable reputation both as an authority in comparative anatomy and as a skilful specialist in the treatment of laryngeal and nasal affections. Among his published writings the follow- ing deserve to receive special mention here:" Outlines of Comparative Anatomy and Medical Zoology," 1869; "Conformation of the Bones of the Orbit.'' 1S70; "On Localization of Diseased Action in the (Esophagus," 1877; and "On the Mechanism of Joints," 1876; "A System of Human Anatomy.'' two volumes, Philadelphia, 1SS2-1884. A. H. B. All-Healing Spring. — Livingston County, New York. Post Office. — Dansville. Access. — Via Delaware, Lackawanna, and West- ern Railroad. This spring is charmingly located among the hills of the picturesque Genesee Valley country of western New York. The region is exempt from malaria. The climate is equable and genial for its latitude. The air is pure and dry. Nights throughout the summer are cool, while the winters are unusually mild with little snow. The soil is dry and porous. The following is the most recent analysis of the water: One United States Gallon Contains: Solids. Grains. Sodium sulphate 0.7a0 Calcium sulphate 432 Calcium carbonate 5.246 Potassium chloride 1 1 < Magnesium chloride -'44 Silica " Alumina and iron (t Volatile and organic matter 0.641 Total solids ^1S0 This water is of marked value in rheumatism, gout, gravel, neuralgia, and neurasthenia of toxic origii.. The water of the spring comes from rocky hen far above any possible source of contamination. Excellent accommodation for visitors to the Springs may be found at the Jackson Health Resort, a sanatorium located on the hillside at an elevation of 800 feet above sea-level. Emma E. Walker. Alligator Pear. — Avocado; Abogate; Aguacate; Pal- ta; Midshipman's Butter. The above are the names of the fruit of Per$( a gra- tissima Gaertn., a large tree of the Lauracew, and they are also applied to the seeds, which have distinct medicinal properties. The genus is related to that yielding cinnamon. It contains about a dozen spe- cies, which grow in the tropics of both contine but the one under discussion alone possesses the prop- erites here described. It is native in many parts .if the American tropics, and is largely cultivated in all tropical countries for its fruit, which is common in northern markets. This is inequilaterally elongated- pyriform, sometimes spheroidal or ovoid, and as large as the very largest pears. The skin has a leathery, rusty-green appearance, or deep purple in some var- ieties. The solitary ovoid seed fills half of the inte- rior, the remaining space being occupied by a ere white pulp, penetrated by numerous gray or greenish veins, of the finest and smoothest fatty texture, highly nutritious and of peculiar flavor. On first trial, it is disgusting to some persons, but they usually become extravagantly fond of it on continuing to use it. The juice of the seeds makes indelible stains on linen, and is used for this purpose. The seeds are larg used in the tropics as a local application in rheumatism and neuralgia, am' some physicians have thus found the fluid extract of service." They are also credited with anthelmintic properties, and doses of fl. o '■ of the fluid extract have been used to expel tenia. H. H. Rushy. Allomorphism.— A term used by Orth to cover the conditions of pseudometaplasia or histological accomr •_'!"_» REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ltM- odation (change of cylindrical cells to flat cells in is a result of pressure, change of flat endothelial ■IN. Bat serosa cells, and pulmonary epithelium into ibo'idal or columnar cells, etc.) and prosopla a oi ive metaplasia (change of colls of the salivary : , i. into secreting cells, the cells of bile-ducts into T-cells, etc.). Dysmorphism has also been used - a synonym. Aldrbd Scott Wakthin. Vloplasia. — A term suggested by Orth to designate ie condition in which the cell-forms normally pre- iminating in a given organ or tissue are replaced cell-forms normally latent, so that the latter :is an apparent metaplasia or heterotopia iasia of Schridde). Such conditions as ;,. presence of squamous epithelium in the pros- ,i,-, bladder, urethra, uterus, trachea and bronchi, of uterine mucosa in the mucosa of the ■rvi\' and on the inner surface of the hymen, inds of gastric mucosa in the esophagus, intes- aal glands in the stomach, pancreatic tissue in ie stomach and intestine, bone in the intermuscular etc., are grouped under this head. Since these isias as a rule always represent tissue of an •ordering directly upon the one affected, they ie regarded as disturbances in the course of the letic differentiation, and not as changes occur- ter differentiation lias taken place — hence, not rue metaplasias. Schridde classes these congenital momalies as heteroplasias; Orth proposed the rin alloplasia or dysplasia. Aldred Scott Warthtx. Allouez Mineral Springs. — Brown County, Wis- onsin. Post-office. — Green Bay. Hotels in Green Bay. The Allouez Springs are beautifully located near he base of an elevation, Astor Hills, in the Valley of in the southern part of the city of Green Bay. inning city, which lies at the head of the bay f the same name, is one of the oldest settlements of Northwest. In the year 166S Father Allouez -tablished a missionary station here, and from that leriod dates the first settlement of the citj-. The are located but a short distance from the site old mission, and are named in honor of its in- repid and worth}' founder. The water bubbles out rmn the hillside at a uniform rate all the year. It emperature of 46° F. A pretty park surrounds' nd an ornamental pavilion covers the spring, which lushes up through an octagonal marble basin. An nt in charge supplies water to the visitors. i i- believed that the Menominee Indians used the ipring for medicinal purposes. The following analysis ras made by the Bureau of Chemistry, I T . S. A., inent of Agriculture, Washington, D. C, June, .'JUT: On~e TJ. S. Gallon- OnxTAiva grains Magnesium chloride 0.99 Magnesium sulphate. ... .4.27 Magnesium bicarbonate. . . s 11 Calcium bicarbonate is 43 Calcium phosphate Trace. Calcium silicate 1 ..50 Sodium chloride 1 .60 Sodium nitrate 2.11 i-sium chloride 17 Ammonium chloride Trace. Liihium chloride Trace. Ferric oxide and alumina 0.07 Silica 0.45 ToUil grains per United States gallon 3S.09 An alkaline-magnesic-saline-calcic water of rare light- ness and softness, possessing marked diuretic and al- terative qualities. In his work on the mineral waters of the United States the writer, Dr. .lames K. (rook, classified this asau alkaline-saline-calcic mineral water. It contains a very fortunate combination of mineral ingredi- ents. The bicarbonate of magnesium gives it valuable antacid and laxative properties. Authorities are agreed that the carbonate oi magnesium is an ex- cellent antilithic in those cases in which uric acid is too abundant. The chloride of sodium anil bicar- bonate of magnesium contribute to render the water diuretic. In diseased states ii - best effects have been observed in diabetes, Bright's disease, disorders of the stomach and liver, and in gout, rheumatism, and vesical calculi. The water is soft and sparkling, anil, as it contains no trace of organic or vegetable matter, is well adapted for general table use. It has also tonic effects. The spring is isolated and is protected from surface water by circular stone walls, well cemented. This wall development extends to the gravel strata, and is capped by a marble slab, sealed except at center or point of overflow into the marble basin. < liven Bay offers numerous advantages as a health resort. Its elevated location renders the air cool and refreshing during the summer months, and malaria is unknown. The magnificent Fox River, which Hows into the bay at this point, is spanned by five bridges. The streets are embowered with avenues of maud old trees, and there are excellent drives in all directions for miles around. Small steam, motor, and sailing yachts, with their burdens of pleasure seekers, ply the placid waters of the bay, forming, during the spring and summer months, a picture of serene and restful beauty. Emma E. Walker. Allspice. — See Pimento. Ally! Tribromide. — Tribromhydrin, tribrompro- phenyl, CJIIir,, is obtained by the action of bromine on oil of garlic (allyl sulphide). It is a heavy, color- less, or faintly yellowish liquid, which is insoluble in water and soluble in alcohol, ether, and. volatile fixed oils. Liquid at ordinary temperature, it solidi- fies at 10° C. (.50° F.). This remedy, containing as it does eighty-five per cent, of bromine, may well replace the alkaline bromides as sedative and anti- spasmodic. In asthma, pertussis, laryngismus stridu- lus nervous irritability, and especially in epilepsy it has had a marked effect. In hysteria on the other hand, it has been of no value. Its dose is two to ten minims (0.13-0.6), given in capsule or on sugar, two or three times a day; or it may be given hypo- dermically dissolved in ten or twenty minims of ether or oil. W. A. Bastedo. Almonds. — See Amygdala. Aloe. — Aloes. The inspissated juice of the leaves of various species of Aloe, a genus of nearly a hundred species, in the family I/Macece, widely distributed through tropical Africa, on the continent and islands, and at least two species extending, through introduc- tion, into Asia, and one into Southern Europe and the West Indies. They are plants of desert or arid regions and strongly succulent, as is common among plants of such localities. They have large, fleshy, bayonet-like leaves, densely arranged in a distichous or tristichous manner, and tall spikes of fleshy flowers, often similarly arranged. All method i of producing aloes from them are based upon the fact that the}' contain two distinct juices, the one thin and flowing at once when the leaves are cut, the other thicker and not readily flowing except under pressure. It is the former of these juices which yields the drug, and which is therefore allowed to flow from the cut leaves without pressure. This juice is then inspissated, either spontaneously 223 Aloe REFERENCE HANDBOOK OF THE MEDICAL SCIENCES or by boiling, and yields a yellow, yellow brown, gray- brown, green brown, or nearly black mass, which may be hard and brittle or of a soft, tarry consistency, or of any intermediate degree. It may be dull, waxy, or glassy, and opaque or translucent, and its odor varies greatly. It is thus seen to be unfitted for any general description. The places of manufacture give the names to the different commercial sorts. It is one of the oldest of medicines; valued — according to tradition — long before the Christian era. Certainly it was known to the Greeks and Romans of the first century, and to the rest of Europe during the Middle Ages. It has always been extensively used and highly prized, as the fanciful names given to many of the older aloes compounds testify. The variety earliest known, socotrine aloes, is, singularly too, the same which is still considered the best in England and America, and is nominally obtained from the same little, obscure, out-of-the-way island that Alexander is reported to have peopled with Greeks, in order to protect and improve its production. Of all the known commercial varieties of aloes, the U. S. P. recognizes the following: Aloe Socotrina or Socotrine Aloes, from A. Pcrryi Baker; Aloe Curussarira or Barbndensis, the Curacao or Barbados Aloes, from .4.. vera (L.) Webb and Aloe Capensis or Cape Aloes, from A.ferox Miller. Barbados aloes, which used to come in gourds, is no longer produced, although the Curacao product, usually packed in boxes, is now sometimes sent in gourds, to imitate the other. They are identical in character. This plant is the most widely distributed of the genus, growing through Northern Africa, Southern Europe, and the East Indies, as well as in the West Indies, where it is cultivated for the pro- duction of aloes. It grows to a height of nearly two feet, with a thick head of bluish-green, blotched leaves, and a dense spike of greenish-yellow flowers, each a little more than an inch in length, and of an elongated, contracted-campanulate form. From the Pharmacographia the following account of the prep- aration of Barbados aloes is quoted: " The cutting takes place in March and April, and is performed in the heat of the day. The leaves are cut off close to the plant, and placed very quickly, the cut end downward, in a V-shaped wooden trough, about four feet long and twelve to eighteen inches deep. This is set on a sharp incline, so that the juice which trickles from the leaves very rapidly flows down its sides, and finally escapes by a hole in its lower end into a vessel placed beneath. No pressure of any sort is applied to the leaves. It takes about a quarter of an hour to cut leaves enough to fill a trough. The troughs are so distributed as to be easily accessible to the cutters. Their number is generally five, and by the time the fifth is filled, the cutters return to the first, and throw out the leaves, which they regard as exhausted. The leaves are neither infused nor boiled, nor is any use afterward made of them, except for manure. " When the vessels receiving the juice become filled, the latter is removed to a cask and reserved for evap- oration. This may be done at once, or it may be de- layed for weeks, or even months, the juice, it is said, not fermenting or spoiling. The evaporation is gen- erally conducted in a copper vessel: ai the bottom of this is a large ladle, into which the impurities sink, and are from time to time removed as the boiling goes on. As soon as the inspissation has reached the proper point (which is determined solely by the experienced eye of the workman), the thickened juice is poured into large gourds, or into boxes, and allowed to harden. " This product varies from an orange brown to a chocolate brown. The latter when broken up ex- hibits the orange brown color also. It is commonly of a waxy luster, dry and brittle or friable, but is occasionally harder and of a glassy luster. Its pecu- liar odor constitutes its most characteristic feature. About sixty-five per cent, of it is soluble in cold water' the solution assuming a purplish-red color. It is the chief source of Aloin, and is regarded as a very good article, though cheaper and less desired than the next A large amount of it is, however, sold under the title of the next. Socotrine Aloes comes from the Island of Socotre although the mainland yields an almost identical article. The drug was formerly brought into Europe via the Red Sea and Alexandria. After the dis- covery of the route around the Cape of Good Hope, it followed the course of commerce in that direction' at present, Socotrine aloes is apt to go to India, and from there to England, with the enormous mass of Indian products. The preparation of Socotrine aloes is said to differ from that of Barbados, in that the heat of the sun is relied upon for its evaporation. Although sometimes imported in large barrels, it is usually in small kegs or small skins. The latter is a cheaper grade, dry and brittle, the former a soft-solid, at least at the center where it is frequently very soft, so as to flow. Si trine aloes is typically of a brownish-yellow or yellow brown, rather than an orange brown like the last, but it is occasionally darker, nearly of a brown black. There should never be any hint of green in its color. If exposed to the atmosphere, it at length becomes hard, through evaporation. Its odor is much finer than that of Barbados. Although not, strictly speaking, less strong, it is less rank and heavy. It is its odor which is relied upon for identification, as well as fur an indication of its quality. At least sixty per cent, of it is soluble in cold water, the solution assuming a yellow color. Exported from India is an article known variously as Moken (or Mochen), East Indian, or Fetid Aim:-, which, although totally unlike the Socotrine variety, has been very largely imported, sold, and used for it, in the United States. It is a disgusting substai black, semi-liquid and of a stinking odor, like putrid animal matter. It contains much albuminoid matter. Its use is wholly indefensible. Cape Aloes is commonly hard, brittle, more or less glassy and translucent. It turns to green black, red black, or even bluish-black. Not less than seventy- five per cent, of it is soluble in cold w r ater, the solution being pale yellow. All official varieties agree in the following characters. They have a saffron-like odor. They should yield not more than 1.5 per cent, of ash and should contain not more than ten per cent, of water. A nearly clear solution should result from mixing one gram with 50 c.c. of alcohol, gently heating and then cooling. If one gram be mixed with 10 c.c. of hot water, and 1 c.c. of this mixture be diluted with 100 c.c. of water, a green fluorescence should be produced upon the addition of a five per cent, solution of sodium borate; or, if 1 c.c. of such dilution be shaken with 10 c.c. of benzol, upon separating the benzol solution, and adding 50 c.c. of ammonia water, a permanent deep rose color will be produced in the lower layer. All, on being dissolved in water or alcohol, yield a crystalline sediment of aloin. All consist chiefly of a resin-like substance which is soluble in alcohol and hot water, but precipitated from the latter solution by boiling. A small amount of volatile oil is found in all. Aloe Purificata, U. S. P., is Socotrine aloes which has been heated, dissolved in alcohol, strained through a No. 60 sieve, evaporated, cooled, and broken up. Aloe Natalensis, or Natal aloes, has a dull surface and a grayish-yellow brown color. It is crystalline and contains aloin, but is weak in odor and taste. Hi putie aloes is a name which has come to be applied to any form having a distinct liver-brown color. Considering its immense importance as a drug, the 224 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alopecia action of aloes is a remarkably simple one. Aside from iis action in the mouth and stomach as a simple hitter, its operation is almost entirely confined to the lower part of the large intestine, where, by its irritant properties, it powerfully stimulates peristalsis ami moderately stimulates secretion. It is therefore a •.ery dilatory, but quite active cathartic. Its action is quite apt' to be griping and painful, especially to those affected with hemorrhoids. Although it has been claimed that this condition can be relieved by the skilful, continued Use of aloes, this is doubtful; while it is certainly true that the condition is thus frequently ravated in a serious degree. A diuretic effect fre- quently ac ipanies the purgation, and is probably hief part due to a mere extension of the irritation. The same is to be said of its emmenagogue effect, and to he remembered that this may lead to abortion. I'll.' intensity of the action of aloes is quite variable, only in different individuals, but in the same individual at different times, and this is especially true when aloin is used alone. This is believed to be to variations in the solution of the aloin. The I. ilc is its natural solvent. Glycerin acts similarly, and either of these solvents, injected into the rectum with aloes, will cause it to take effect. Taken inter- nally, alkalies increase its activity, as does iron. Aloes can be absorbed by the subcutaneous tissue, excreted into the bowel, and become active. Because of its slowness, and its limited field of action, it is usually preferred to combine it with some differently acting cathartic. Its peculiar mode of action indicates that aloes is especially useful in those cases of constipation which result from torpidity of the intestinal muscles. The dose of aloes is exceedingly variable, according to the patient and the effect desired, being from 0.03 to 0.6 gram (gr. ss.-x.). The Pharmacopoeia provides a large number of preparations, as follows: Liquids. — Tinctura Aloes, containing ten per cent. of aloes and twenty per cent, of licorice root, made with dilute alcohol, dose 1 to 4 c.c. (fl. 5. i~i-); Tinc- tura Aloes et Myrrhas, containing ten per cent, each of aloes, myrrh, and licorice root, made with alcohol; dose the same as of the last. Solids. — Extractum Aloes (aqueous), dose 0.03 to 0.2 gram (gr. ss.-iij.); Extractum Colocynthidis Compositum, containing purified aloes 50 per cent., extract of colocynth 16 per cent., resin of scammony and soap, each 14 per cent., cardamom 6 per cent., dose 0.06 to 1.0 gram (gr. i.-xv.); Piluke Aloes, each containing 0.13 gram (gr. ij.), each of aloes and soap; Pilulse Aloes et Ferri, each containing 0.07 gram (about gr. i.) each of aloes, dried sulphate of iron, and aromatic powder, with a little confection of rose; Piluke Aloes et Mastiches, each containing 0.13 gram (gr. ij.) of aloes, 0.04 gram (gr. §) mastic, and 0.03 gram (gr. ss.) of red rose; Pipulas Aloes et Myrrhae, each containing 0.13 gram (gr. ij.) aloes, 0.06 gram (gr. i.) myrrh, and 0.04 gram (gr. f) of aromatic powder; Pilulas Rhei Composita?, each containing 0.13 gram (gr. ij.) rhubarb, 0.1 gram (gr. iss.) aloes, 0.06 gram (gr. i.) myrrh, and a little oil of peppermint. H. H. Rusby. Aloinum. — Aloin. "A neutral principle obtained from aloes, varying more or less in chemical com- position and physical properties according to the source from which it is obtained. Chiefly prepared from Curasao aloes." (U. S. P.) Aloin is a minutely crystalline powder, lemon yellow to dark yellow, having a slight odor of aloes, intensely bitter, slightly hygroscopic and soluble in water and alcohol. It exhibits slight differences as de- rived from the different varieties of aloes, and the Pharmacopoeia describes only that from Curasao aloes (barbaloin). Aloin is the principal active constituent of aloes, Vol. I.—U and its action and uses are essentially the same. The dose is about one-fourth that of purilied aloe . II. II. ROSBY. Alopecia. — Alopecia is a partial or general loss of hair, from any cause whatever, and that in sufficient quantity to be noticeable to the naked eye. The word "alopecia" is derived from the Creek d\u>7T7)S, meaning fox. Why this word has been used to express baldness, it is difficult to say. tine explanation might be that the fox is said to have, normally, twai bald spots over his eyes, and another, that he is especially liable to i he di i.i e. The term as it. is used to-day covers a broader field than it did formerly. It includes not, only all varieties and degrees of dystrophies and atrophies of the hair of the scalp causing baldness, but also similar conditions of the hair upon any other part of the body. In text-books the alopecias are usually divided into two main classes, congenital and acquired. In the present article this classification is not followed, but we will attempt to give a more scientific one instead. Alopecia may be due to a local disease of some hairy part of the body, and in this case it would be limited throughout its whole course to the part in which it commenced, or it may be the result of disease elsewhere, and then the consequent baldness is only incidental to the other affection. This line of thought also evolves two principal classes: (1) Alopecke essentiales, idiopathicoe sive primaries; (2) Alopecias symptomatica^ sive secund- arke. The first class includes the congenital and senile forms, and those primary affections of the hair that are premature, comprising alopecia presen- ilis, alopecia pityrodes, alopecia areata, folliculitis dccalvans, and dermatitis papillaris capillitii. (We are well aware of the fact that strict logic would really not permit alopecia pityrodes to be placed in this class, but it stands out so prominently among those diseases causing baldness that for prac- tical purposes it may be classed among the essential alopecias. Similar objections could be made against the placing of alopecia areata among the "idiopathic premature alopecias," and yet we find it there by the consent of many good authorities.) The second class contains first, alopecia toxica, which includes those instances of alopecia caused by the use of drugs like mercury and acetate of thallium and also those caused by the toxins of systemic infections such as syphilis, typhoid fever, etc.; second, alopecia dynamica sive destructiva, in which loss of hair is principally due to atrophy caused by mechanical force, such as pressure atrophy (lupus erythematosus), or to the destruction of tissue the result of suppura- tion (gummata, epitheliomata, sycosis, etc.), or to severe local inflammation (acute eczema, erysipelas, etc.); and finally, alopecia neurotica, which follows traumatic or functional nerve injuries. The following represents a brief schedule of this classification: I. Alopecia: Essentiales, Idiopathicce sive Primariai. 1. Congenita. 2. Senilis. 3. Prematura. II. Alopecia Symptomatica; sive Secundaria;. 1. Toxica. 2. Dynamica sive destructiva. 3. Neurotica. Alopeci.e Essentiales. — Alopecia Congenita. (Depilatio Congenita, Atrichia, Oligotrichia). — Con- genital alopecia is a rare affection. It may be com- plete, the new-born babe being wholly devoid of hair, even of lanugo. After some time has elapsed, from a few months to a few years, let us say, lanugo hairs may begin to form, and later on, full-sized normal hairs may make their appearance. It may, however, 225 Alopecia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES be the case that growth of hair never takes place. This has been frequently found to be true where there was only a partial alopecia at birth. In an instance like this the individual bald patches may multiply in number until they spread over the entire scalp, and they often show a tendency to increase in size. In connection with this malady, anomalies of the teeth and nails are often observed. Crocker reports the case of an individual who had only four molar teeth, and was never known to have perspired or shed tears. Alopecia congenita represents one of the evidences of arrested development ; there is a marked hereditary tendency, and more than one member of the same household may suffer from it. Schede 1 is apparently the only one who ever pub- lished the results of a complete microscopical exami- nation of this disease. He found the sebaceous glands well developed, in many places sending their open ducts through the somewhat atrophic epidermis; in some of these rudimentary hairs could be observed, in others the papilUe were merely indicated. The cutis surrounding this region was changed into a coarse areolar tissue interspersed with granules and fat cells. The prognosis in the universal congenital alopecia is said to be not as bad as in the partial affection. Treatment can only be hygienic, and is limited to aiding the general nutrition processes. Alopecia Senilis (Calvities Senilis) — With the advent of old age, a loss of hair not only of the scalp, but also of the eyebrows, the genital and the bearded region is observed. Women are not as extensively affected as men. While it is true that at the decline of human life an increase in the growth of hair is often seen, it is equally true that this growth never takes place upon the scalp. As a rule the hair becomes gray before there is any sign of senile baldness, which begins upon the top of the vertex, at its junction with the occiput. The coarse hairs begin to fall out, at first from a small circular area only; this loss of hair spreads at the periphery, presenting a picture like the full moon shining through the clouds, and later on assuming the form of the tonsure of a friar. The disease spreads forward along the vertex, and descends laterally upon the temples and the region above the ears, and finally also invades the occiput. As a rule, it leaves a small rim of normal hair encircling the lower lateral and posterior parts of the scalp. The coarse hairs are replaced by lanugo hairs, but these also finally drop out. The scalp is then left as a smooth, shining surface, thinner and tenser than before, but still freely movable over the cranium. The mouths of the follicles may still be seen for some time, but they too shortly disappear. The whole process is incidental to the retrogressive nutrition changes of senility. The prime factor is an obliterating endarteritis, which here means occlusion, lack of blood supply, atrophy, and death of these structures. From the pathology of this condition it is plain that treatment is of no avail in averting the loss of hair. Alopecia Prematura;. Alopecia Presenilis. — When the symptoms of the last-described malady appear in younger persons who do not show any other evi- dences of the degeneration of old age, it is called "alopecia presenilis." Its course and pathology are the same as in the senile form, and therapeutic efforts are as useless. The wearing of stiff headgear, such as derbys and silk hats, is considered by some as a cause of this affection. They argue not only that the hard brims impede the circulation, by pressure upon the blood-vessels encircling the scalp, but that on account of their tight fit the air from expiration becomes so deteriorated as to be obnoxious. This factor may be remembered when a case presents itself. Invigorating treatment, and the avoidance of injurious diet and habits, may in some degree retard the progress of the disease. Active cell metab- olism should be encouraged. Alopecia Piti/rodes sice Alopecia Furfuracea Capil- lilii. — Our reasons for placing this affection among the essential premature diseases of the hair causing baldness have already been given. Its true nature is by no means definitely settled, as shown by the various designations given to it, e.g. seborrheal eczema inflammatory seborrhea, seborrheal dermatitis, besides those that are now obsolete, as, seborrhea sicca, seborr- liea oleosa capitis, acne oleosa, and others. It is one of the most frequent causes of baldness. It is not con- fined toany particular age, but still is oftenest seen in persons who are at the end of the second, or at the beginning of the third decade of life. Women suffer from it more frequently than men. Elliot gives the relative frequency of the disease in the two sexes to be as five women to four males. Michelson states that women are not as often attacked as men. Symptomatology. — One of the first conditions no- tire, 1 by a patient is an increased scaliness of the scalp commonly known as dandruff. Associated with this is an obstinate itching, and a sensation of burning heat. The pityriasis increases as the years go on, when the sufferer complains that more hairs than usual fall out when combing. A woman will soon notice that her braids grow thinner at the ends, and that hairs com- mence to project from them. This phenomenon is due to the fact that the life duration of the individual hairs (a duration which, normally, is about four years) has become less than normal; therefore they do not attain the usual length. The hairs taking the place of the shorter-lived ones grow, in the course of time, not only smaller, but also thinner. They lose their luster and natural curliness, and finally are replaced only by lanugo hairs. An associated senile alopecia may hasten their disap- pearance. During all this time the dandruff increasea in quantity, but at the appearance of the lanugo con- dition it stops suddenly, as if the disease had spent its energy. The pityriasis consists of whitish scales made up of epithelium, sebaceous matter, and dirt. According to the proportion of sebum in them, they may feel greasy or comparatively dry. The amount of dandruff is a good indication of the severity of the disease. In addition to the itching, heat, and headache, there is now experienced a feeling of tension all over the scalp. Michelson has observed increased pers- piration in some cases at this period. Although, strictly speaking, the loss of hair begins simultaneously over the whole scalp (Pincus, Michel- son), there are certain areas that are more rapidly and more intensely invaded than others. As a rule, there are two principal centers of development, and both lie in the median line of the top of the head; the anterior one begins about one-half inch behind the border of the hair, and runs backward; the other one starts from the junction of the vertex and occiput, ami progresses forward, so that there remains a bridge of hair between, which connects both parietal region, and still remain even when the disease is far advanced; but it also finally breaks down. The occiput and lateral portions of the hairy scalp are not seriously attacked. The small bunch of hair in front of the anterior bald spot is also quite persistent. The anterior temporal regions, "the corners of the hair," may form two additional starting-points. Pathological Anatomy. — According to the descrip- tion given by Pincus the epidermis is not thickened but made rather thinner than normal. Elliot found processes of vacuolation in the epidermic cells, and infiltration with wandering cells. The granular layer is seen to be slightly increased. The subcutis is the seat of marked inflammatory changes, as shown in the dense, small, round-cell infiltration which is 226 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alopecia arranged especially around the blood-vessels, partic- ularly around those supplying the hair follicles and their papillae. The hairs in themselves show nothing characteristic. They differ in no way from those that have undergone the process of physiological death, pt that in some instances the roots are smaller, atrophied, and have pointed ends, instead of showing the nollowed-ouf knob of the healthy hair. Increased brittleness may also be observed; but this probably occurs only in bad cases, and then only in the ad- vanced stages of the disease. Later on, as evidences of a chronic inflammation make their appearance, the small round-cell infiltration is replaced by a dense net work of fibrous tissue, which gives the feeling of tightness to the scalp, and prevents its being lifted up between the fingers. The subcutaneous fat is greatly increased in quantity. Ft iology. — Some diseases, such as syphilis, diabetes, typhoid fever, etc., are predisposing factors. French writers consider "arthritisme" as an important cause. Heredity also plays quite a role here. Any condition or malady that leaves the system in a weakened must naturally be looked upon as furnishing a favorable chance for the invasion of the disease. Lad hygienic surroundings, defective cell metabolism, neglect of proper care of the scalp, general malnutri- tion, increased ingestion of sugars, loss of sleep — all of these have to be looked upon as probable pre- disposing factors. How really sensitive the hairs of the scalp are is shown by the loss of their healthy luster and oiliness after a single protracted dissipation, with its attendant loss of sleep and subsequent general depression. Numerous are the organisms described by those who have attempted to verify the parasitic nature of the disease. Malassez considered his flask-shaped bacillus (called by Sabouraud Bacillus asciformis) as the cause of alopecia pityrodes. Unna holds that alopecia pityrodes is identical with his eczema seb- orrhoicum, and is caused by the morrococcus or mulberry coccus. Merrill, in connection with Elliot, found a diploeoccus with sufficient frequency to be able to attach to it some etiological importance. Sabouraud, after some painstaking experiments, believed that he had established the identity of some follicular affections hitherto regarded as separate diseases — i.e. comedones, acne, seborrhea, alopecia pityrodes, alopecia senilis, and alopecia areata. He describes a punctiform bacillus almost resembling a coccus, lft in length and 0.5/i in diameter. It has the power of penetrating deeply into the hair follicles and into the sebaceous glands, while, according to him, the flask-shaped bacillus of Malassez is confined to the funnel-shaped enlargement of the mouths of the diseased follicles. He sums up his explanation of the pathogenesis of alopecia pityrodes by stating that the presence of the microorganism described by him first causes an irritation, and thus a hypersecre- tion of the sebaceous glands; then there follows an hypertrophy, and by further invasion, a progressive papillary atrophy, with malnutrition and atrophy of the hair producing cells, hence death of the hairs that are formed, and cessation of the growth of new one-;. Right here it would seem appropriate to mention the fact that the parasitic theory of alopecia pity- rodes was first advanced by Lassar and Bishop 2 after some experiments in which alopecia followed the in- unction of a mixture of vaseline and finely cut hairs, taken from a tyr cal case of this disease. In the case just mentioned alopecia appeared in the third week, and could be transmitted from the first series of animals to others. Michelson remarks that he was able to produce the same effects with rancid olive oil. Saalfeld, 3 repeated the experiments of Lassar and the bacteriological studies of Unna and Sabouraud. He was able, like Lassar, to produce a loss of hair, but not a typical alopecia pityrodes. He also suc- ceeded in producing the same conditions with simple non-rancid oil, and even with the somewhat vigorous strokes of a brush. Using rancid oil, he obtained the same effects as Michelson. Ee has found micro- organisms which may be considered identical with tho e of Unna and Sabouraud, but he looks upon them as incidental. He was unsuccessful in proving that they produced alopecia pityrodi Fig. SO. — Alopecia Areata. (From a photograph of one of the author's cases.) The direct exciting cause is probably a local exogen- ous toxemia from organisms situated in the skin; and the predisposing cause and the more important one, an endogenous or metabolic toxemia or an exogenous toxemia from the digestive tract, making the soil favorable for the organisms directly concerned in causing the inflammatory process. Diagnosis. — The disease may be readily recognized by its occupying usually the median portion of the scalp, the lateral and posterior parts being compara- tively free from the furfuraceous scales always pres- ent in greater or less quantities, and from the sensa- tions of itching and heat. It is distinguished from senile, and more espe- cially from presenile alopecia, in that these two forms begin upon the vertex of the head, wdiile the anterior portions are invaded much later. There is no pity- riasis in these diseases, and the loss of hair is more rapid. Psoriasis does not attack the scalp as a whole. Its lesions are usually isolated and sharply limited ; its scales are silvery and dry and comes off in lam- ellae; and it never attacks the scalp alone. Eczema seborrhoicum is especially noticeable by the margin along the front of the hairs; this margin is more or less continuous and covered with yellowish greasy scales. As a rule, the chest and the back are affected at the same time. The diagnosis is some- times impossible. Alopecia syphilitica, while it may be seen all over the scalp, is, however, generally situated upon the 227 Alopecia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES sides and the occiput; often the external halves of the eyebrows and the eyelashes fall out. Alopecia areata can hardly be confounded with alopecia pityrodes. Like the preceding it completely lacks the furfuraceous desquamation. Pincus has called attention to the disproportion of the sharply pointed hairs, those that are so small that in cutting the hair they escape the shears or the barber; and those which, on account of their length are clipped, and therefore present to view a dull- pointed end. If the proportion is as 1:8 of hairs of thirteen centimeters length, and as 1 :10 in those hav- ing a length of from five to eight centimeters, the shed- ding is abnormal; and this circumstance, in connection with the other symptoms described, gives the diagnosis of alopecia pityrodes. The way in which it is recog- nized in women has already been alluded to under the heading of Symptomatology. Prognosis. — The disease is curable, but can be com- bated only by energetic and long-continued treatment which may last weeks, months, or even years. As it it not in human nature to spend the time and energy necessary for the cure of an affection where the dam- age done is simply an offence to the esthetic, the disease as a rule, is permitted to run its regular course to the end, which is perhaps put off for a few years by intermittent attempts at treatment. Heredity, and the appearance of this form of alopecia in the earlier years of life, render the prognosis less favorable. Treatment. — We will not enumerate all the reme- dies advised for the cure of alopecia pityrodes, but simply lay down the principles for its treatment, and cite one or two examples. Any other plans and methods advocated can then be readily appreciated by the reader. The first step must be to remove the pityriasis. This procedure removes at the same time a good many organisms, and by the mechanical force applied, massages the scalp, and hence helps to re- move some of the inflammatory exudates. The next step is to apply some antiseptic medicament which should not only cover the scalp, but should also penetrate, if possible, into the hair follicles, so as to reach organisms situated there. Through the washings, and the applications of antiseptics which are usually dissolved in alcohol, the natural oil of the scalj) will be removed. This must be replaced, and this replacing constitutes the third and last step of the treatment. An ointment having as a basis vaseline or lanolin is rubbed into the scalp. It is a good plan to add to this some antiseptic, so as to have the dis- eased parts in constant contact with a germ-de- stroying agent. This treatment has to be repeated daily for from one to six weeks; then once every other day for a similar period of time; then three times a week; after that once a week, and this latter must be continued for a period of years for, as stated above, if the scalp is not treated energetically and persistently the dis- ease is certain to recur. No method, however, can resuscitate the atrophied hair-producing structures; but the simply diseased ones may be restored to health, if treated before the changes are too far advanced. Twenty or more years ago Unna recommended a simple remedy, which, according to him, is attended with good results. It consists simply of an oint- ment of ten per cent, precipitated sulphur in unguen- tum pomadini. The hair is parted first in a sagittal, then in a coronal direction, the parts being a distance of about one centimeter away from each other, and tin- salve is lightly spread along the furrows. This is done every night. The scalp is washed every three or four days to cleanse it from the scales and the salve. In the second week, or later, according to circum- stances, the intervals between the applications be- come longer and longer, until finally treatment is stopped altogether after a cure is thought to have been obtained. The method laid down by Lassar meets all the indi- cations for treatment. The scalp is washed daily with a good tar soap for at least ten minutes, warm water being used at first, and the lather then rinsed off with cool, and finally with cold water. After this the hair and scalp are thoroughly dried — this is very important. Now a solution of one-half per ci corrosive sublimate in equal parts of glycerin and ; water is used, being applied to the scalp with some friction. This is followed by the use of a solution of one-half per cent, of ^-naphthol in absolute alcohol. As the parts are now completely dehydrated and poor in fat, the latter has to be replaced and now any fur- ther antiseptic added is taken up very eagerlv on account of the dehydration. Lassar recommends the following: fy Acidi salicylici, 10; Tincture benzoini, 3; Olei bubuli, 100. In severe cases the corrosive sublimate solution may be used several times dur- ing the day. If there be a tendency to great greasi- ness of the scalp, resorcin of from three to five per cent, strength is suggested, instead of the /3-naphthnl or salicylic acid in the ointment; or, it may be added to the same, the percentage of the latter being then of course reduced accordingly. The combination of resorcin and salicylic acid is, besides, very appro- priate from a pharmaceutical standpoint, for resorcin has the tendency, when used alone, and especially when combined with alkaline media, to turn red in color; a change which does not take place when in union with acids. When the hair is very dry sulphur acts better than resorcin. Of course, when sulphur is used, the wash- ing with corrosive sublimate is omitted. The sul- phur in that case is incorporated into the pomade in combination with salicylic acid and also with resorcin, if we choose. As the greasy ointments are often objectionable to women, we may add the ingredients to a basis of a lower melting-point than lard or vase- line; as, for instance, benzoinol or liquid albolene. This treatment of the scalp must be repeated daily for at least one week, and, in more marked cases, for as long as six weeks; after this once every other day; then three times a week; and finally once a week will be sufficient, but this must be continued for months if necessary. Corrosive sublimate 1 to 1000 in bay rum is a cleanly preparation and usually gives satisfactory results. It is to be used as a daily dressing of the hair. Alopecia Pityrodes Universalis. — Under this name Michelson' described a variety of the former disease affecting all the hairy regions of the body. Kaposi had observed a similar condition in connection with seborrhea. The disease may begin like a simple alopecia pityrodes affecting the top of the head, hut si urn the whole scalp becomes involved, and si- multaneously, or a little later, all the hairs of the body begin to fall out; at the same time there is an abun- dant production of pityriasis in the parts affected. Lanugo hairs take the place of those that have dis- appeared, and in places the stumps of hairs I have been broken off may still be seen. This affec- tion somewhat resembles a universal alopecia, areata, but differs from it in the pityriasis present. and in the fact that the scalp is tense and tightly stretched over the cranium, while in alopecia areata it is thin and readily movable. A greatly debilitated system seems to lie at the bottom of this malady. The prognosis is not unfavorable; the new hairs that grow in may be different in color from the old ones. The diagnosis is readily made, if it be remem- bered in what points it differs from alopecia areata. The pathology is essentially the same as that ol alopecia pityrodes localis. Michelson has noticed a peculiar brush-like deform- ity of the ends of the diseased hairs, a deformity which he attributes to the affected papillae being unable to furnish enough cement substance to li"M 228 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Alopecia the individual cells together. The lower parts of the hairs show an increa ;e in nuclei and pigment. Besides the local treatment, which consists of in\ igorating l>aths, as ft)! 1 instance these of salt water, and that special treatment described under the local form of this alFection, particular attention is to be directed to the general nutrition, which must be improved. Alopecia Simplex. — Pineus described instances in which there is a general loss of hair of the scalp; the crop of hair becomes thinner and thinner, just as it does in alopecia pityrodes, but there is no pityriasis in nection with the loss of hair. This latter fact made it seem proper to give this special form of the disease a separate name. The treatment is similar to that in alopecia pityrodes, only the shampooing - remove dandruff may be omitted as unnecessary. Alopecia Areata (Area celsi, area circumscripta, i accidentalis, tinea decalvans, teigne pelade, pelade). — The term "alopecia areata," as it is used to-day, is rather vague and ill defined. Several diseases are probably included under it. The affection is a disease of the hairy parts of the body, producing a loss of hair in circumscribed areas, which commence as small spots and gradually in- crease at the periphery, the underlying skin being apparently little or not at all affected. The regions most frequently attacked are the scalp, the beard, and the eyebrows. The disease may occur on any part of the body where hair is found. The loss of hair may be partial or complete. The mild cases are usually limited to the head, beard, and eyebrows. Crocker, in order to substantiate his belief in a connection between alopecia areata and ringworm, has pointed out that it is more frequent in those countries where the latter prevails (France and England), while both affections are far less frequent in Germany and America. Men are more often attacked than women, persons between the ages of tin and twenty-one more frequently than others; dark-haired persons suffer more from the affection than blondes. Symptomatology. — Constitutional or local prodro- mal symptoms are absent as a rule; there may be some malaise, loss of appetite, headache, slight itch- ing, and other paresthesia?. H. Schultze, 5 who ob- served the disease on himself, made note in his case of a unilateral headache upon that side, which, later on, became invaded by alopecia areata. The parts of the scalp most generally affected are those surrounding the junction of the occiput and the parietal bones. There is no symmetry in the lesions as a rule. The formation of the individual patches is about as follows: A person may notice that in a certain spot his hair conies out very freely. He observes a bald space. He attempts to pull out some hairs, and finds that they can be removed very easily and wholly without pain. Afterward the hairs may fall out spontaneously along the periphery of the small patch first seen. The patch grows larger, rapidly or slowdy, and in all directions. The increase in size may progress more rapidly in one direction than in another, thus creating oval or irregular patches. There may be only one patch, or there may be several, beginning at the same time, or, as is usually the case, there may be successive crops of bald spots. The areas of baldness are from one-half to two inches in size, but by the coalescence of several areas very large patches are sometimes formed. Individual areas are not always very sharply defined from the surrounding healthy structures in the first stages of the malady. The periphery is surrounded for a short distance by a thinner crop of hair. There may be some few healthy hairs left even in the center of the bald areas, hairs which cling to their papilla;. Some broken-off hairs projecting from their follicles are often noticed upon close inspection. The skin at the seat of the affection is smooth, shiny, thin, and can readily be lifted up between the fingers. It looks paler than the normal skin, and on being pricked with a needle blood oozes less readily. There are no vesicles, crusts, or scales, no efflorescences of any kind. In some feu- cases I have observed a slight caling, redness, and some edema at the beginning Of the disease. The level of the affected skin is felt to be below that of the neighboring normal skin. This is duo to the fact thai tie skin has sunken in, on account of I lie ab ence of so many hairs in the now collapsed hair follicles, and not, as some believe, to an atrophy of the cutis. The nervous impressions are not impaired. The tactile, temperature, and pressure senses may be slightly increased ( Michelson). Neumann, however, has observed anesthesia. \\ hen the disease at a given patch has come to a standstill, the hairs at the periphery become more normal in number and cannot be as easily plucked out as before; the affected area is now sharply defined. The period of baldness of such a patch is, as a rule, of several weeks' duration, and if at the expiration of this time there are no signs of regeneration, it is difficult to determine when the hairs will make their reappear- ance. The malady may go on for years and years. Recovery has been observed after a period of from ten to fourteen years, and even after a much longer time; it may, however, never take place. Reproduction of healthy hair begins almost always at the periphery and progresses from without inward. First, small lanugo hairs begin to appear. These, after a short struggle for existence, may fall out again, to be replaced by stronger and longer hairs. This replacement of the new hairs by others may repeat itself several times before the normal hairs finally make their appearance, and these latter may even then lack color for a long time. The affected area may long after be recognized as the site of a previous alopecia areata. A seborrheal eczema condition sometimes precedes the alopecia area but in my experience it occurs only in a small percentage of the cases. Alopecia areata of the other hairy regions presents analogous phenomena. The beard, eyebrows, axil- lary and pubic hairs may fall out. All the hairs of the body may disappear, thus constituting the al- opecia maligna of Michelson. Pathology. — Nothing characteristic of this affec- tion can be obtained from an examination of the hairs. They show the same simple atrophy as seen in the hairs shed in the physiological way. In some the roots are not bulb-shaped, but pointed, a fact to which we have already called attention, in connec- tion with the pathology of alopecia pityrodes. My observations of the microscopical changes of the skin were reported to the Ninth International Medical Congress at Washington (1887). Many pieces of skin were taken from seven different patients. In spite of the clinical appearance of the dis- ease, the presence of an inflammatory process in every case could be observed. S. Giovannini and Sabouraud have also found perivascular small round- cell infiltration, consisting of mast cells and mono- nuclear leucocytes. This, according to Sabouraud, goes to show fhe presence of an agent with decided chemotactic influences upon these cells, an agent probably emanating from a microorganism. In my sections, the subcutaneous tissue was normal, the lymphatics were somewhat dilated and contained micrococci. Whether they have any etiological relationship to the pathological phenomena, I have so far been unable to demonstrate. Some hair follicles showed replacement of the normal hair by lanugo. The hairs in some were broken, or stubbed and split. The lower parts of the follicles were devoid of pigment, this explaining the loss of color of the returning hairs during convalescence. In cases of permanent alopecia of long standing, hair follicles and sebaceous glands had been destroyed. 229 Alopecia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The blood-vessels showed a thickening of their walls. Etiology. — There is in dermatology hardly a single disease whose nature is so much disputed as that of alopecia areata. Three views are held in regard to it: first, that it is a trophoneurosis; second, that it is of parasitic origin; third, that what we understand under alopecia areata to-day is not a clinical entity at all, but that under this name are grouped several diseases, some of which are neurotic, while others are parasitic. In my opinion every case of alopecia that com- mences as a small spot and gradually increases in area by extension at the periphery and shows the clinical characters I have described, is due to the local action of an organism. In support of the first view are cited the nervous prodromal symptoms, such as neuralgia, headache, and the various paresthesia?, and the fact that loss of hair in patches often follows nerve injuries. Kap- osi enumerates many instances of this kind. Best known are the experiments of Joseph and Mibelli, who observed alopecia following the excision of the second cervical ganglion. Moskalenko and Ter- Gregoryanitz {Vrach, 1899) have produced typical alopecia areata in dogs, cats, and rabbits by per- forming the same. operation, and also by cutting the nerve roots. Injury to the peripheral nerves pro- duced no typical alopecia areata, as the patches that showed themselves were not round. If the disease were always due to nerve injuries, the triangular form, corresponding to the area of supply of a given nerve, should be more frequent. Besides, there arc undoubted cases in which the lesions spread without regard to blood-vessel or nerve supply. According to my view of the subject, the cases of circumscribed loss of hair following nerve injuries are not instances of alopecia areata, if we understand this term to mean an affection in which the hair falls out in round patches which spread at the periphery, and only such cases should be called cases of alopecia areata. The fact that regeneration progresses from without inward has been brought forward as an argument against the theory; if justly so, remains to be seen. Another argument against it is the absence of all inflammatory symptoms usually seen upon the sur- face — i.e. vesicles, scales, crusts, etc.; but as already mentioned, an inflammatory process is always present. Numerous organisms have been found. As early as 1843, Gruby had described his Microsporon au- douini, but it was found that it represented one of the forms of the ringworm fungus. Others who called attention to parasites are Malassez (1875), Thin (1881, bacterium decalvans), von Sehlen (18S4, areacoccus), mvself (1SS7), and Vaillard. Vincent, Nimier (18S9), etc. In 1S9G Sabouraud 6 brought to notice an organism which he named " microbacillus alopecia? areata?," and not being certain as to its etiological importance, "le micro- bacille de l'utricle peladique." He admits that it may be identical with Unna's and Hodam's organism found in comedones, and in acne. In the following year (1897) he stated that in his opinion comedones, acne, seborrhea, alopecia pityrodes, and alopecia areata are all caused by the same organism, varying only in intensity and location. As reported to the American Dermatological Association, I have experimentally produced small areas of alopecia with all the objective characters of alopecia areata by the subepidermal injections of Staphylococcus epidemicus albtis. The patches did not extend beyond the area injected. In support of the parasitic theory, frequent refer- ence is made to the instance of contagion as cited by Crocker, many French authorities, and by Bowen and Putnam 7 of this country, and again by Bowen. 8 In France the disease lias been observed especially in (lie army, and is believed to have been due to the same hair-clipping machines having been used, or to the same caps and helmets having been worn. .Sabouraud has observed that many patients applying for treatment at the Hopital St. Louis came from the same section of the town, and that some had employed the same hairdresser. The epidemic in an asylum, described by Putnam, is remarkable. Sixty-three out of sixty- nine girls were infected, and there was no trace of ringworm. A girl, who was believed to have spread the disease, left the institution, and went home where in a short time her stepfather became infeel In the mean time the epidemic at the asylum had come to a standstill. A'few years after, this Ban girl was again received at the institution, and in a very short time twenty-six out of forty-five children showed evidences of the disease. Hutchinson and Crocker think that there is some relationship between ringworm and alopecia areata. I have seen several examples of an almost simul- taneous appearance of the disease in two or more of the same family. Diagnosis. — A typical case can be readily recog- nized by the lesions being round and spreading at the periphery. The thin, smooth, shiny skin, sunken beneath the niveau of the surrounding health}- skin, and showing no signs of an inflammatory process makes the diagnosis easy. Alopecia areata has to be differentiated from ringworm, favus, syco syphilis, folliculitis decalvans, and the loss of hair after traumatism. Alopecia maligna must be dis- tinguished from alopecia pityrodes universalis (vide above). In ringworm we find dermatitis, broken-off hairs, and the ringworm fungus under the microscope; in favus, also, the organism producing it, as well as the yellow cups, scar tissue, and a grayish discoloration of the atrophied hairs. Folliculitis decalvans pre- sents evidences of follicular inflammation and sear- tissue formation. Alopecia syphilitica shows irreg- ular patches, not depressed, especially affecting the outer portions of the scalp and the eyebrows; besides these, there are concomitant symptoms of the disease. Cases of the falling out of hair in patches, in con- sequence of nerve injuries, have been observed, and the characteristics of the resulting bald spots were similar to those of the ordinary cases of alopecia areata. The clinical history of the manner of forma- tion of the patch is, however, different. I consider those cases only to be true examples of alopecia areata in which the patches grow by extension at the periphery. Prognosis. — As alopecia areata tends to a spon- taneous recovery in the majority of cases the prog- nosis is favorable. Even if regeneration does net show itself for years, hope should not be entirely abandoned, for regeneration may ultimately take place. This was true in several instances, where new hairs grew even after a decade or more from the beginning of the malady. It is my experience, how- ever, that if a patch remains quite free from lanugo hairs for several months, it shows that the follicles are probably destroyed and that there will be a per- manent alopecia. The older the patient, and (he longer the area has been affected, the graver becomes the outlook as to recovery. The possibility of relapses must not be forgotten. Treatment. — On account of the fact that recovery is often spontaneous, it is exceedingly difficult to appreciate the value of any therapeutic agent other- wise than by means of a long series of observations. A host of remedies has been recommended. Inter- nally, arsenic, cod-liver oil, tonics, and jaborandi may be tried in connection with dieting, physical and mental hygiene. While such a therapy may not have any direct effect upon the cause of the lesions, it may help to render the system more resistant to the disease. Tincture of jaborandi is administered to 230 Kill KKKXCK HANDBOOK ( >!•' TIIK MKDICAL SCIK.WKS Alopecia produce a local hyperemia of the pale patches who e blood-vessels are abnormally contracted. The older methods <>f I oral treatment wore addressed to stimulate the nutritive processes of the part; lav, when the parasitic theory prevails, para- siticides are used. Chrysarobin, in my opinion, ds out far above any other remedy. It is must ctual when incorporated in vaseline or lanolin; much more so than when combined with liquor ta percha or traumaticin. As a rule, a six- to ten-per-cent. preparation is applied daily for one or two weeks, and then stopped for a short time to erve if the disease has been cured. If lanugo ■a do not appear soon, or if the hairs at the pe- riphery continue to fall out or can be easily pulled out, the treatment is continued. Care should be taken that the application does not reach the eyes, as a, re conjunctivitis might follow. Because of this ible danger it cannot be used upon the eyebrows. it" recommends for these that carbolic acid be ned biweekly. The slight mahogany discoloration rved around the neck and in the face after the of chrysarobin is the first danger signal of an approaching dermatitis. The remedy should now either be stopped at once, or the strength of the oint- | be reduced. The hairs around the periphery Id be removed as soon as they become loose. 1 believe the great majority of the cases can be cured within two or three weeks by this treatment if seen at an early stage. Croton oil, which is a pure irritant, be of benefit in chronic cases. It should be I with olive oil, equal parts, and applied every day until a dermatitis is produced. Balzer and Storianowitch have obtained good re- sults with a fifty-per-cent. solution of lactic acid in water or alcohol. The affected parts are first freed from oil with alcohol and ether, and the remedy is then applied with a swab of cotton until slight redness appears. Besides this the scalp is washed with a one- cent. bichloride solution. After the stimulation has become well marked, the applications of lactic acid are interrupted for a few days. Boric acid line is spread upon the surface in the intervals. The alcoholic solution is said to be the less painful. Recovery was obtained fifteen times out of nineteen is, in from two to three and a half months. Lan- ugo hairs made their appearance at the end of the md week, at the earliest. McGowan recom- mends tricresol used pure upon the scalp, and upon the face in a fifty-per-cent. solution. He was led to use this remedy from his experience with pure car- bolic acid. Scarification with subsequent application of a •ion of corrosive sublimate 1:2,000, as in erysipe- as, seems to be a rational mode of treatment, but •till there is some danger here of infection with pus irganisms. Injections of bichloride 1:40, made at ii'.fcrent points, are recommended by Moty of Paris. Finsen of Copenhagen, who obtained such brilliant 'csults, especially in lupus vulgaris, with the applica- tion of concentrated violet light rays was successful n treating alopecia areata by the same method. lesfld who followed Finsen in his treatment, states ;hat it cures alopecia areata in two months, instead jf the three to six months necessary by the use of older methods. Brisquet uses oil of cinnamon (Chinese) and sul- phurous ether 1:3. He avoids washing the scalp !o exclude humidity (after the hairs have ceased to ill). The sulphur preparations are often of prompt ind decided value; e.g. an ointment of one to two hams of precipitated sulphur to an ounce of vaseline, rubbed well into the scalp daily, after a thorough washing of the whole scalp with soap and water. In my opinion, as already stated, cures can be obtained more quickly, and with greater certainty, rom the use of chrysarobin than by any other method. After the hairs have ceased to fall out, some stimulat- ing and antiparasitic application should be applied for a few months. Relying upon internal medicine and hygienic measures alone I believe to be a serious mistake and accountable for many cases of permanent alo- pecia. Such measures if employed should invari- ably be accompanied by a vigorous local antipari n ic i real merit. Folliculitis Decalvans. — Within the last decade French authors especially have called attention to the hair follicles being attacked by some affection whose nature still remains obscure. Each authority in turn has considered the individual disease before him as a new one, and has stamped it with a new name, so that in wading through their literature, we meet with a formidable array of names, "the sum of which has brought despair to every humble reader." 10 Some of these affections are identical, some represent only novel aspects of well-known diseases. The following are a few of the titles given: "Follicu- lites et perifolliculites agminees destructives du follicle pileux" (Brocq); "folliculite epilante" (Quin- quaud); "folliculites et perifolliculites decalvantes agminees (Brocq); "alope'cie cicatricielle innomineV (Besnier); "acn6 decalvante" (Besnier, Lailler, Rob- ert); "lupoid sycosis" (Milton, Brocq); "ulerythma sycosiforme" (Unna). A description of a few of these types may suffice. " Pscudo-Pelade," Simple Folliculitis Decalvans. — This affection somewhat resembles alopecia areata, but on close inspection a mild folliculitis and peri- folliculitis may be noticed. There are rose-colored, inflammatory tumefactions, soft to the touch; the hairs fall out, and are easily plucked out; they are not broken; there is a marked atrophy in the older spots; these are depressed, shiny, and, unlike those of alo- pecia areata, hard and irregular, and, as a ride, smaller. The disease spreads in an irregular manner. "Folliculite Epilante" of Quinquaud. — This form corresponds to the acne decalvante of Lailler and Robert. It resembles the former with the addition of suppuration in the follicles. Besides the scalp, the beard, axilla;, and pubic regions may be involved. Permanent alopecia appears also, caused by the cicatricial destruction of the hair-producing areas. The bald spots are round or irregular; along "their periphery or in islands of healthy hair within them, small pustules, perforated with a hair, are usually to be seen." Quinquaud found micrococci, but was unable to establish their causative effect. "Alope'cie cicatricielle innominee" of Besnier is almost identical with Quinquaud's disease. It is slightly more superficial, more chronic, and more obstinate; the cicatricial changes are greater; the margins are not sharply defined; the disease spreads by continuity. Besnier himself considered both diseases the same, but Quinquaud stated that they are not identical. "Dermatitis Papillaris Capillitii." — Under this name Kaposi has described a follicular disease appear- ing at the junction of the nape of the neck and the -alp, invading the latter often as far as the vertex. It is doubtful whether this affection is a clinical entity, or simply a variety of some other disease. According to Kaposi it commences in the form of an isolated papule of the size of a pin's head. These papules later on aggregate to form elevated red plaques, which are quite hard and from which the hairs project in brush-like bunches. The hairs are not readily removed; they break and are atrophied; pustules may be noted in places. After the disease has invaded the scalp and lasted a long time, papil- lomatous vegetations are formed, two to three centi- meters in diameter, covered with crusts from which oozes a foul-smelling secretion. Abscesses may de- velop also. Microscopical examination shows an extremely vascular papillary outgrowth, very much resembling 231 Alopecia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES granulation tissue. The disease finally progresses to the formation of connective tissue and scar tissue, with the subsequent death of the invaded hair fol- licles. Nothing is known positively as to its etiology. It occurs at all ages and in both sexes. It is undoubt- edly a local parasitic affection. Diagnosis. — The disease would have to be differen- tiated from a papular syphilide. Coccogenic sycosis and eczema do not show such a firm induration, and their clinical history is different. Prognosis. — The disease has no tendency to spon. taneous recovery, but it is usually slow in its progress- The general health remains unaffected. The lesions may return after excision of the affected area. Treatment. — Mechanical removal of the growth is the only means of treatment so far as we know. Curetting, excision, and cauterization with chemi- cal, electric, or actual cautery must destroy the base of the disease or there will be recurrences. A*-ray treatment has given good results in my hands. Ai.opeci.e Symptomatica. — Alopecia Toxica. — In the course of some infectious diseases there are noticed grave disturbances of nutrition from the toxins in the system, disturbances which also affect the growth of hair. It seems as if the toxins them- selves can produce baldness, when it occurs during the attack of the infectious disease, as in alopecia syphilitica. The loss of hair may be subsequent to the general grave nutrition disturbances, as when it appears during convalescence after typhoid fever. This form of alopecia is also seen in the cachexia; that occur with malignant disease, chlorosis, etc. Some drugs may produce it, as mercury and acetate of thallium. S. Giovannini and others have observed general loss of hair following the administration of doses of 0.1 of this latter remedy given for the sup- pression of tuberculous night sweats. Alopecia sypliilitica is perhaps of sufficient interest to warrant a short description, on account of its com- parative frequency, its often very typical course, and the importance of making a correct differential diag- nosis. We refer here only to that variety that is noticed at the beginning of the secondary period. It may be complete, all the hairs of the scalp, the pubic region, and the axilla; disappearing, or the hair may fall out in larger or smaller patches which arc usually symmetrical. It is highly characteristic of this affec- tion that it invades especially the outer border of the scalp, the temporal, parietal, and occipital regions, and, unlike alopecia pityrodes, avoids the top and front of the head. What is stated by Fournier to be almost typical of syphilitic alopecia is the falling out of the outer halves of the eyebrows on both sides. Any concomitant, syphilitic lesions will aid in dis- tinguishing it from alopecia areata, which it often resembles. Its prognosis is good, even the complete alopecia yielding to proper antisyphilitic treatment. Alo- pecia pityrodes, however, often follows in its wake. It is obvious that attention must be paid, to this according to the rules prescribed for this disease. The prognosis in all the alopecia; due to toxins is very favorable. Cessante causa, cessat effectus. The underlying cause should therefore be removed, if possible. Alopecia Dynamica sive Destructiva. — Loss of hair may be caused by toxins in connection with local destructive processes. It is then purely mechan- ical, due to the loss of tissue or to pressure atrophy. This may occur in severe or deep local inflammations, as in long-continued sycosis, aggravated forms of acute eczema, erysipelas, impetigo contagiosa, or in inflammations accompanied by ulceration spreading over the surface, as in pustular, tubercular, and gum- matous syphilides, lupus vulgaris, lepra, the kerion of tinea trichophytina, and ulcerating neoplasmata, most frequently epithelioma. Finally, the hair fol- licles may be choked to death, so to speak, by some chronic inflammatory processes which do not sup- purate, but have a tendency to scar-tissue formation causing atrophy, due to the mechanical cutting off of the blood supply. Lupus erythematosus, sclero- derma, lichen planus, and the keratosis follicularis of Brocq belong in this class. The prognosis depends upon the severity of the local primary disease. In most of them the "resulting alopecia is permanent. The treatment is that of the underlying affection. Alopecia Neurotica. — Traumatism to an individ- ual nerve, or to the central nervous system, as a fractured skull, concussion of the braiii, shock, or their combinations, may cause loss of hair — a 'loss which may be complete, as in the three case:: cited by Michelson, one of which showed not even a single lanugo hair; this occurred after a fall, followed by a period of unconsciousness lasting for a year. It. may Ik- unilateral, or partially limited to the area of dis- tribution of a single nerve; in the latter case the resulting bald spot is, as a rule, triangular. Fisher observed complete alopecia of the extremi- ties following gunshot wounds. These cases wen- remarkable from the fact that they were preceded by a decided increase in hair growth. The so-called functional psychoses and neuroses. such as melancholia, migraine of long standing, hemiatrophy of the face, produce discoloration and falling out of the hair. Persistent neuralgias di the same, but here the alopecia is never complete. There always remain lanugo hairs in the affected are Some cases that are looked upon as examples of alope- cia areata undoubtedly belong in this category. A. R. Robinson References. 1. Schede: Archiv fur klinische Chirurgie, Bd. xiv 2. Lassar: Monatshefte fur praktische Dennatologie, 1882, i 3. Saalfeld: Virchow's Archiv, vol. clvii. 4. Michelson: Zeimssen's Handbuch der Hautkranken. 5. Schultze: Virchow's Archiv, vol. lxxx. 6. Sabouraud: Annales de Dermatologie et de Syphiligraphie, 1S96, i. 7. Bowen and Putnam: Journal of Cutaneous ami Ge&ito* urinary Diseases, 1S97. 8. Bowen: Journal of Cutaneous and Genito-urinary I 1899. Jessner: Monatshefte fur praktische Dermatologie, 1900. 10. Robinson: Morrow's System of Genito-urinary I Syphilis, and Dermatology. Alphozone. — Succinvl peroxide, succinic dioxide, (COOH.CH 2 .CH,.CO),b 2 , similar in structure to hydrogen dioxide, the hydrogen atoms being i by succinic acid radicles. It occurs in the form of a white, fluffy, odorless, crystalline powder, soluble in thirty parts of water. It is a powerful oxidizing agent, and consequently an antiseptic and deodorant, but does not effervesce in the presence of organic matter. It is employed as an intestinal antiseptic in typhoid fever and dysentery, and as an external application in the treatment of ulcers and inflamma- tions of the mucous membranes of the nose aid throat. For the latter purpose a solution of 1 3,000 to 1-1,000 is emploved in the form of sprav. T. L.S. Alps. — The extensive and lofty group of mountains occupying the central region of Europe, in S land. Savoy, Southern Bavaria, and Western Am tria and separating Italy from the colder countries h he to the north of it, presents to the invalid a variety of places of resort, some chiefly serviceable during the summer months, some during the winter season, and some of them available as sanatoria aj all times of the year. The climatic and other pcculiariti of this region are discussed in the articles treating of the several Alpine resorts, such as Arosa, Engadine. Meran Vevey, etc. 232 RE ERENCE IIW'DHOOK OF Till: MEDICAL SCIENCES \ I in ii hi \lston, Charles. — Born in 1683 in the west of otland. Studied medicine in Leyden, Eolland, ,1,-r the teaching of the celebrated Boerhaave. lr ing his stay of three years in that city he formed strong friendship with Alexander Monro; and , two Mien, upon their return to Scotland, formed ,. project of greatly strengthening the College of Unburg as a center of medical education. With this n view they secured the cooperation of Ruther- il, Sinclair, and Plummer. It is undoubtedly true it tilt' ureal celebrity which the Edinburgh Sell, .el Medicine subsequently attained should !»■ attribu- I in large measure to the efforts made by these five >n and to the wise and skilful manner in which they ,1 the business. Alston filled t In- chair of m\ and materia mediea in the reorganized and performed this duty acceptably up to the no of his death, November, 22, 17(1(1; but the ititude of posterity is due to him, not so much for contributions to this department of medicine, as r the reorganization work to which reference has been made. A. H. B. \ltcratives. — Formerly this term was applied a group of remedies supposed to exert a very de- led action in removing morbid conditions of the sys- tnand promoting the patient's general well-being. It ,~ understood to mean "remedies which would rees- hlish the healthy functions of the animal economy thout producing any sensible evacuation." With e advance in physiology and therapeutics and the cognition of the importance of excretion as a factor promoting health, a new conception of the term and alteratives were defined as "agents which ter the course of morbid conditions and modify le nutritive processes while promoting waste." v most modern therapeutists the term has been cted as meaningless, or at least too indefinite i be tolerated in any scientific classification of •UgS, and at best alteratives may be defined as remedies, such as arsenic, iodine, and mercury, Inch act in a way to correct disordered metabolism id promote repair." In addition to the drugs just entioned, this class included sulphur, antimony, )ld, guaiacum, colchicum, calcium chloride, and ater, to which, were the class still recognized, would ■ added thyroid extract and other organothera- mtic agents. T. L. S. Althaus, Julius. — Born in Lippe-Detmold, Ger- i my, on March 31, 1833. He pursued his medical tidies in Bonn, Goettingen, Heidelberg, Berlin, ienna, Prague, and Paris, and finally settled in ondon in 1857. In 1866 he established, in the eighborhood of Regent's Park, a " Hospital for Ipilepsy and Paralysis." His death occured on June I. 1900. Of his published writings the following deserve to e mentioned: "A Treatise on Medical Electricity," lird edition in 1873; " Diseases of the Nervous Sys- •m," 1X7!); "On Failure of Brain Power," fifth edi- inn in 1S9S, and "The Value of Electrical Treatment," hird edition in 1S99. A. H. B. Althasa. — Marshmallow. "The root of Althma offi- inalis L. (fain. Malvaceae)" deprived of the brown orkey layer and small roots, and carefully dried " l'. S. P.) The Marshmallow is a tall, perennial alt-marsh herb of temperate European sea coasts, t is also largely cultivated, sometimes for ornament, nit chiefly for its root, in Southern Europe. The oot of commerce is from six inches to nearly a foot ong, usually about half an inch in greatest thickness, simple and regularly tapering. It is nearly white, rom the removal of the outer bark, and marked with several broad grooves ami numerous small, brown, slightly elevated spots. It is more or less fuzzy with loan, hair-like, partly detached ba I fibers. Ii snaps readily, owing in ii- large amount of starchy parenchyma, bul the parts still cling together by their tOUgh bat liber.-,. It ha- a sweetish and Strongly mucilaginous taste. It i.-, about one-third gum and another third starch, with about ten per cent. of peel in, eight pea' cent . of SUgar, and one pel- cent, of asparagin. In properties are wholly nutritive ami demulcent. There IS no pleasanter ad.ju\ a at than the official Syrupus Althoece of five-per-cent. strength. The leaves and flowers are also rich in gum, and both are much used in domestic practice in Europe for poultices and demulcent drinks. IIesry II. Rusby. Altitudes, High. — See Climate and Climatology. Altmann's Granules. — These are granules of an acid-protein nature present in the cells of nearly all normal tissues, the chief exceptions bring the cells of unstriped muscular tissue, squamous epithelium, ami the cells of the pyramidal portion of the kid- ney. The granules are demonstrated by fixing in for- mol-Muller fluid (formalin, 2, in Midler's fluid, 98) for one week, then staining skin sections (5/<) in aniline acid fuchsin for three minutes at 60°C, and differ- entiating with picric acid alcohol (two minutes) or ammonia (half a minute). According to Henry Beckton 1 , the absence of Altmann's granules from a new-growth, originating in cells normally con- taining them, is an indication of malignancy. On the other hand, " the presence of Altmann's granules in all or nearly all the essential cells of a new-growth is usually associated with non-malignancy or only with malignancy of a special kind or limited degree." In a tumor the diagnosis of which lies between inflam- mation and sarcoma the presence of Altmann's gran- ules indicates the former, the absence of them points to sarcoma. 1. Eighth, ninth, and tenth reports of the Cancer Research Laboratories of Middlesex Hospital, 1909-1911. Aluminum. — Aluminum is a metallic chemical clement, with symbol Al, and atomic weight 27. It is not found free, but in contamination (chiefly as silicates). It is white, has a valence of three, melts at about 626° C, somewhat resembles tin in colors and is a constituent of several useful alloys. General Medicinal Properties of the Com- pounds of Aluminum. — As compared with the ma- jority of the heavy metals, aluminum exerts but an insignificant constitutional action — one useless in med- icine, and not certainly recognizable even in poisoning by aluminum compounds. All the evidence there is of constitutional action by this metal is that, in toxic doses of alum, there have been observed along with the symptoms of local irritation, tremors, spasms, fainting fits, and, in severe cases, death, with dispro- portionately slight local lesions. Locally, aluminum compounds are astringent — the freely soluble, such as alum, highly so, but yet with less conjoint irritation than is usual with astringent metallic salts. The main therapeutic use of aluminum preparations is for a local astringent effect, for which purpose these compounds combine potency with freedom from bad taste, undue irritation, or power to stain. The Compounds of Aluminum Used in Medi- cine. — These are the hydroxide, sulphate, and the aluminum and potassium sulphate (potassium alum). Aluminum Hydroxide. — Aluminum hydroxide, Al 2 (OH) , is official in the U. S. P. as Alumini Hydrox- iihim. It is prepared by precipitation, a boiling hot aqueous solution of alum being poured into a similarly hot solution of sodium carbonate. The precipitate of the hydroxide is then washed with hot distilled 233 Aluminum REFERENCE HANDBOOK OF THE MEDICAL SCIENCES water, drained, dried, and pulverized. The product is a " a white, light, amorphous powder, odorless and tasteless, and permanent in dry air. Insoluble in water or alcohol, but completely soluble in hydrochloric or sulphuric acid, and also in potassium or sodium hydroxide. When heated to redness it loses about thirty-four per cent, of its weight." (U. S. P.) This preparation, from its insolubility, can exert active prop- erties only through chemical conversion. Locally applied, it operates as an absorbent powder, develop- ing, possibly, a faint astringency. Its employment is almost exclusively German, and consists in its application to the skin in inflammatory affections. Aluminum Sulphate.— The salt, A1,(S0 4 ) 3 + 16H 2 0. is official in the U. S. P. asAlumini Sulphas. It occurs as "a white, crystalline powder, or shining plates, or crystalline fragments, without odor, having a sweetish and afterward an astringent taste, and permanent in the air. Soluble in 1 part of water at 25° C. (77° F.), and much more freely in boiling water, but in- soluble in alcohol. When gradually heated to about 200° C. (392° F.), it loses its water of crystallization (4.3.7 per cent, of its weight). The aqueous solution of the salt has an acid reaction upon litmus paper." (U. S. P.) Aluminum sulphate is powerfully astrin- gent, and also antiseptic. Its use is local only, as a conjoint astringent and detergent, or, in saturated solution, as even a mild caustic in simple hyperplasias. Aluminum and Potassium Sulphate. — This double salt, A1K(S0,) 2 + 12H,0, is official in the U. S. P as Alumen, Alum. Alum is in "large, colorless, octahedral crystals sometimes modified by cubes, or in crystalline fragments, without odor, but having a sweetish and strongly astringent taste. Soluble in nine parts of water at 25° C. (77° F.), and in 0.3 part of boiling water; it is also freely soluble in warm glycerin, but is insoluble in alcohol. When gradually heated, it loses water; at 92° C. (197. 6° F.) it fuses, and if the heat be gradually increased to 200° C. (392° F.) it loses all its water of crystallization (4.5.5.5 per cent, of its weight), leaving a voluminous, white residue. An aqueous solution of alum has an acid reaction upon litmus paper." (U. S. P.) Alum is decomposed by the alkalies and their carbonates, lime, magnesia and magnesium carbonate, potassium tartrate, and lead acetate. The salt is highly astrin- gent, and, internally, in dose of from oi-ij. (4.0-S.O) or more, is promptly and efficiently emetic, with little nausea or depression. In large concentrated dosage it is an irritant poison, but death is rare. Alum is principally employed locally as an astringent. For limited application to an accessible part a smooth crystal may be swept over the surface, but more com- monly aqueous solutions are used, ranging in strength from one-half of one per cent, to three or four per cent., according to the sensitiveness of the part. A domestic but serviceable form of application is alum curd, made by boiling alum in milk, one part to sixty, until coagulation ensues, then straining and applying the curds like a poultice, between layers of fine linen. Or the curd may be obtained by mixing 30 grains (2.0) of powdered alum with the white of an egg. Alum may be used almost universally for astringent purposes, except that as a gargle it is objectionable because of an injurious action upon the teeth, and as a collyrium because of its attacking and softening the tissue of the cornea wherever the protective influence of the epithelium may be wanting, as in case of abra- sion or ulcer. Internally alum may be used as an emetic in the doses stated above, and has been held for a century — off and on — to be of peculiar avail in lead colic, abating all the symptoms, even to break- ing the tendency to constipation. For internal as- tringent medication alum is nowadays comparatively seldom used, other astringents being preferred. The <\ cence and becoming dark on exposure to light ami air; it is also slightly soluble in alcohol, and it pre- cipitates albumin and gelatin, the precipitate being soluble in excess of either. Alkalies cause the for- mation of a flocculent precipitate of aluminum hydroxide. Alumnol combines the astringency of alum with the antiseptic power of naphthol. Externally it may lie applied to ulcers and wounds, having a strong tend- ency to check exuberant granulations and to stim- ulate healing. Although it coagulates albumin, it does not form a slough in the wound if spread thinly, because the precipitate formed is soluble in excess of albumin. For such local application it may be em- ployed in from two to ten per cent, strength, diluted with starch or talc. For abscesses a ten-per-cent. solu- tion has been used as a dressing. Applied in one-half to two-per-cent. solution as a spray it is very efficacious in ordinary catarrhal conditions of the nasal and pharyngeal mucous membranes, lessening the ci in- gestion and the edema and relaxation of the soft palate and uvula. For insufflation in chronic rhi- nitis or laryngitis, a ten to twenty per-cent. snuff with camphor and starch may be used. In gonorrhea' a solution of from one-half to four per- cent, strength may be injected into the urethra, after the acute symptoms have subsided. Alumnol has REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amar.yllldaieie I n suggested as an intestinal astringent, but data rning its internal use are wanting. \V. \. Babtedo. ilum Rock Springs. — Santa Clara County, Cali- I da. ICCESS. From San Jose by electric railway seven , northeast. San Jose is a terminal point and center to all parts of the Easl and Pacific i ,st. San .lose is called the Garden City of Cali- u'a. springs are located on the western slope of the si range in a romantic canon called Alum Rock . M>n Park, the pride of San .lose. This is a canon r yground of 1,000 acres, a city reservation six , t of the town in the Coast .Mountains. Here sixteen mineral springs already developed and id free to the public. The nearness of the to San Jose 1 and the excellent accommoda- fered at the hotels, with the many natural iges of climate and scenery, make the Alum l k Springs a favorite resort for tourists, summer itors, and invalids. The summer temperature is above 90° F., and in the winter it is never too I .■ for comfort. Trout and mountain quail abound, irding good sport for rod and gun. The analyses of four of the springs are given below: Alvelos. — The milky, resinous juice of Eupho heterodoxa Miiller (fain. Ewphorlnaceae). This Bra- zilian product is employed in its own home as an heroic application to "cancerous" tumors, which are there, for the most pail, syphilitic ulcers. The drug i- a powerful irritant, and sets up inflammatory suppura- tion. Many years ago an attempt was made to intro- duce it to scientific medicine, but the allempt was abandoned. If. II. Rusby. Alypin. — Trade name of the monohydrochloride of benzoyl - tetramethyldiamino -ethylisopropyl alcohol, („ II „".o..\,.llci = iriu.vi ii.rr.ii , : ,'c, iu :< K I) ,1 II XiCH ,).,11CI. It occurs as a white crystalline powder, of bitter tasie, melting at 109° C. (336°+F.). It is highly hygroscopic and consequently very freely soluble in water and alcohol. Aqueous solutions are neutral and do not become turbid on the addition of a small quantity of sodium bicarbonate. Solutions may be sterilized by boiling for a brief period; if heat is continued, however, the alypin is decomposed. It has a strong bitter taste. Because of its hygroscopic nature, alypin should be kept in securely stoppered vials to exclude the air. From 2 to 4 per cent. s.ilut ions are stable; weaker ones soon become mouldy. Alypin is one of the many local anesthetics which have appeared as surrogates for cocaine. It is claimed to equal cocaine in intensity and duration of anesthe- Soda Spring. Grs. per gal. Blue Sulphur Spring. Grs. per gal. White Sulphur Spring. Grs. per gal. ' .~;i!i Condiment.' Grs. per gal. a 1.21 m sulphate .S3 ni bicarbonate 10.57 ; Hum chloride 126.94 : lium bicarbonate 267 . 12 I lium sulphate hia (with spectroscope) slight trace en chloride .50 nil sulphate gnesium carbonate 7.45 I ;cium carbonate 20.82 I lium .sulphate .18 ii mi phosphate 3.04 n and alumina (carbonates and phosphates) .... .35 acid (with spectroscope) well marked trace Totals ! 4:i!l ill ionic arid gas, cubic inches per gallon 215.62 -*■ hydrogen sulphide gas, cubic inches per gallon 1.19 3.27 1.30 3.03 7.; 68 159.45 13.68 slight trace 39 5.00 19.52 .20 1.17 .49 well marked trace 3S.S9 115 44 13.77 very slight trace .31 7.81 12 as 1.03 .97 .29 well marked trace 3.52 5.88 146 67 25 11 116.51 trace 24 . 30 1 5 45 19.91 -,r, ,;'i .32 .58 ,vell marked trace 278.04 174.03 5.60 195 S7 98 50 10 31 414.64 At Alum Rock there are two thermal sulphur rings which have a temperature of S5° F. They e used for bathing purposes. Sulphur plunge baths all sorts are to be provided. The waters at this resort have gained considerable natation in the treatment of rheumatism, anemia, ilorosis, chronic malaria, nervous prostration, and •bility. They ought, furthermore, to be useful in e hemorrhagic diathesis, to menorrhagia, etc., on count of the iron, alum, and acids which the waters mtain. Emma E. Walker. Alum Root. — Heuchera. Under this name the lizome of Heuchera Americana L. (fam. Saxifragacece) used as a simple astringent, by reason of the four- •cn per cent, of tannin which it contains. It is a ooked, tuberculate rhizome, five or six inches long id half an inch thick, of a purplish or reddish color, itbin and without. The plant grows abundantly in le Eastern United States and is represented through te West by other species of the genus, with similar imposition and properties. The dose is from one to air grams fgr. xv.-lx.). Either water or alcohol will xtraet its tannin. H. H. Rusby. sia; that its use does not affect the accommodation, produce mydriasis or intraocular pressure, and that it is less toxic than cocaine. Injections are followed by a transient hyperemia. In intralaryngeal and urethral intervention alypin seems to be an ideal substitute for cocaine. It is used externally to the unbroken skin or mucous membrane, as well as hypodermically and subcutaneously, and also to induce spinal anesthesia. Indications for its use are the same as for cocaine. Solutions should be freshly prepared and may be combined with any one of the suprarenal preparations. Locally alypin is used in 10 per cent, solutions; hypodermically, 1 to 4 per cent.; instillations into the eye, 1 to 2 per cent. Alypin nitrate may be combined with silver nitrate when treating urethritis or cystitis and to anesthetize the urethra before the introduction of instruments. T. L. S. Amaroids. — See Active Constituents of Plants. Amaryllidaceae. — The Amaryllis family. A family of some seventy genera, growing chiefly in tropical or warm countries, and very largely cultivated for floral decoration. Many species, especially of the Narcis- 235 Amaryllidaceie REFERENCE HANDBOOK OF THE MEDICAL SCIENCES sus group, are known to be poisonous. They are almost unknown to medical literature, but the agave or century plant is an important source of fermented and distilled liquor in Mexico. The family may be expected to yield important additions to the materia medica. H. H. Rusby. Amaurosis. — See Blindness. Amber. — Succinum. Arribra flava. A fossil resin produced by Pinites succinifer Goeppert (JPityoxylon sucdniferum Kr.), and other tertiary and long extinct Coniferm. Amber has been found from Alaska westward to Greenland, and southward in New Jersey and Maryland, but our supplies come chiefly from the shores of the Baltic. It is east up by the waves, fished from the bottom, and mined upon the shore and under the edges of the sea. The grades that are unfit for ornamental purposes, and the trimmings, are used medicinally. Amber is found in hard, brittle tears and lumps of more or less rounded but often irregular shape. They are usually small, rarel}' exceed a few grams in weight, and vary very much in clearness and transparency. They often contain coarse impurities, vegetable remains, and dirt. Occasionally entire insects are beautifully preserved in them. The color of amber is generally yellow or brownish, but varies from almost white to nearly black; it is rarely greenish. The external or natural surface is usually rough or irregular, the interior often beautifully transparent. It is harder than most resins, has no odor or taste, breaks with a conchoidal fracture, and is capable of receiving a high polish. It is insoluble in water and cold alcohol, but may be dissolved in boiling alcohol, benzol, etc. It softens at a moderately high temperature, but does not melt until 29° C, when it begins also to decompose. The use of amber itself in medicine is long past. It is sometimes an ingredient of fumigating powders or pastilles; directions also for making an ethereal tincture are in pharmaceutical works. The oil of amber {Oleum Succini) is an empyreumatic liquid, obtained by dry distillation and purified by distilla- tion from water. The crude oil is a thick, dark red, offensive-smelling liquid. The redistilled oil is a colorless or pale yellow, thin liquid, becoming darker and thicker by age and exposure to air; having an empyreumatic balsamic odor, a warm, acrid taste, and a neutral or faintly acid reaction. Specific gravity about 0.91.5. It is readily soluble in alcohol. It is extensively adulterated. Internal dose, 0.2 to 0.5 gram.-(ni iij. viij.=gtt. v.-xv.) — it is said to be stimulant and antispasmodic. Externally it is rube- facient, and is occasionally used as an ingredient of liniments. The residual pitch, "amber resin," left after the distillation of the oil, is dissolved to make a slowly drying, but very hard and durable var- nish. Succinic acid is also one of the products of the disintegration of amber. H. H. Rusby. Ambergris. — Ambrn grisea (gray amber). A pe- culiar fatty material, found in lumps, generally on the surface of tropical seas, occasionally in the intes- tines of the sperm-whale, Physeter macrocephalus Shaw, where it is supposed to be a pathological formation. The balls are often of concentric struc- ture, and in appearance and position are analogous to concretions found in other animals. Pieces vary in size from small fragments to great masses of fifty kilograms or more in weight. It is a waxy, tasteless sulwtance, crumbling, but also softening in the hand, having about the consistency of some gallstones, its color usually grayish or brownish, streaked or spotted wiih whit-. Odor slight, peculiar, not nauseous. At the temperature of boiling water it melts, and at a higher one is dissipated, leaving but little residue. Soluble in alcohol, ether, fixed and essential oils, etc Ambergris consists to the extent of about eighty- five per cent, of a peculiar non-saponifiable, crystalliz- ahle fat, ambrein, besides small amounts of extractive benzoic acid, etc. Ambergris is almost wholly used in perfumery, but has been employed as an antispasmodic of the type, though it is probably weaker than that. Its medical use is nowadays not worth serious i i In perfumery, like musk, it has the property of holdiiic and developing the vegetable odors. The dose may be accepted as from 0.2.) to I gram (gr. iv.-xvi.). A tincture would be a suitabl preparation. H. H. Risby. Ambidexterity. — This is to be equally and indif- ferently efficient with either hand. From time to time ambidexterity has been extolled as universally desirable; and some educators consider that the development of the left hand, along with that of right, should be begun with the entrance of little children into our schools. It is therefore worthy discussion in what manner right-handedness has become habitual among ninety-six per cent, of human- kind; and whether ambidexterity is a really de- sirable human qualification. The lower animals, at least those which have not been taught tricks, use their forepaws indiscrimi- nately; the cat strikes at a fly indifferently with either paw; the squirrel manipulates its nuts quite as indif- ferently. Even in monkeys and gorillas, which mosl of all animals use the forepaws as hands, there is no preferential use of, or superior expertness in, the left or the right hand. But animals can be tutored to one or the other paw. The dog is taught to shake hands with the right paw; the monkey to si manwisc, with the musket butt at the right shoulder. Among microcephalic idiots, in whom the small headedness is due to arrested development, lclt- handedness or ambidexterity has been found to reach a proportion of fifty per cent. But as we rise in the evolutionary scale of normal creatures, and we exclude disease, ambidexterity progressively gives way to single-handedness, generally right-handedn Sir' James Crighton-Browne holds that "by superior skill of his right hand man hath gol himself the victory." To try to undo his dextral , eminence were to make for devolution. Glimpses of right-handedness in man are, it manifest in the bronze and paleolithic age-. It is evident in the arts of the ancients — Assyrian, Gre- cian, Egyptian. Historic investigation shows that all peoples, however savage, have uniformly used by preference not only one but the same hand — the n It is said that some races to-day manifest either- handed ness; but this is very doubtful. It has I said that the Japanese are by practice and bj ambidextrous; but Baron Komura has given positive assurance to the contrar}'. Crighton-Browne abi quoted believes it doubtful whether, "strictly spi ing, complete ambidextry exists in any fully di oped and civilized human beings, though so very close approximations to it occur." Most hui beings, then, are right-handed; though of COU there are those of great intellectuality who are in more or less degree ambidextrous, having educated themselves to this end. But these latter are exc tional and by reason of the peculiar and special train ing they have subjected themselves to. The origin of right-handedness lies much d than the individual's voluntary selection as to v\ hit her he will use his right hand or his left, or whether he will be ambidextrous. The reason is to be found largely in human anatomy, in the position of the heart, and in the cerebral structure and organization, which all voluntary movements are directed and controlled. The heart and the great arteries are 236 REFERENCE HANDBOOK OF TIIF. MEDICAL SCIENCES Ambulances ,,1, though in the primordial organism from ,,.|, thr ran- has evoluted there was, it serins, no . Ii asymmetry. The savage, from time iminemo- ',1 has protected his heart with his left, his shield /■liit his aggressive motions have been made with ,t, his spear arm. The modern savage, too, : iugn he bears no shield — which would be useless modern weapons — fires his musket uniformly mble sense) from the right shoulder, sighting > h his right eye; the sword also is wielded in the (hi hand. Such things are now. as they have been oul history, absolutely fixed in our military . torn. Hie sec. md important fact is that in human I ttomy all voluntary movements are directed and , trolled in the cerebral structure and organization. I the brain's two hemispheres, the right presides, as of the decussating nerve fibers, over the of the body; while the left brain presides , r the right side. And functional differences in sides are connected with and contingent upon ces in the two hemispheres. The left brain. , all right-handed people, is more highly developed ie right brain. It is said that this greater i elopmenl of the left brain in the right-handed is due t the fact that the heart, being on the left side of the nds its blood with greater force and directness i tii.' left brain; this is a fact worthy of consideration i .ugh not very weighty, because the (low of blood ise of the brain is pretty well equalized in the if Willis. An important anatomical point is that in right- ) tided people the speech center is situated in oca's convolution, in the cortex of the left frontal be; while in left-handed people the speech center in the same position, but in the right frontal lobe. !>W, it has been found that damage to Broca's con- lution in the left hemisphere has deprived the ht-handed man of speech, which is unimpaired in ■ left-handed man in the same circumstances: the t-handed man would suffer contrariwise, were the in the right side. The hand and arm centers the brain are intimately linked in the cortex witli e speech centers. Crigliton- Browne's inference is at the preferential use of the right hand and arm voluntary movements is due to the leading part ken by the left brain. " We could not get rid of r right-handedness, try how we might — it is woven the brain." Of course there are professions and trades in which ertain amount of ambidexterity is essential. The mist, in playing the fugues of Bach, must strike down on the key board) almost the same notes th the fingers of the left hand as he does with those the right; and he has to hit harder too, for the base il the piano are more heavily- wired than those the treble. A certain amount of ambidexterity tial also in the surgeon; yet this gift has its -advantages withal, as when a colleague skilled this way admitted that before doing a thing he -i.d appreciable time wondering which hand to iploy. It may be objected, in favor of general training in obidexterity, that when a clerk, for example, lost 3 writing hand, he would then not be debarred from rning his living. On those rare occasions of right- ind mutilation, however, there will in good time How, through education and practice, an adequate tvelopment of the right brain, with a very fair skill the use of the left hand. John B. Hubeb. Amblyomma. — A genus of eyeless ticks, family I . which is common on cattle, particularly warm countries. .1. americanum occurs from aborador to Florida. It burrows into the skin id may T cause tumors. Ticks of this genus are so known to carry germs of certain infections iseases. See Arachn'ida. A. S. P. Amboceptor. — Amboceptors or immune bodies are antibodies of I'.hrlieh's third order. They are .!.■ . I- opi'd in the serum as one of the re till nt the inject ion oi cells of various kinds. The amboceptor i- belie ed t.. consist of t v. o elements, the ci implement! iphilr group which combines with the alexin or complement , and the cytophile group whereby the immune body be- comes attached to the cell. Amboceptors are al-o called cytolysitis. for it is by means of these substances that the complement is joined to the cell body and thus permitted to exercise its lytic effect. It is evi- dent therefore that lysis is impossible except in the presence of both tin mces. The amboceptor is thermostabile. that is, it is nol destroyed by heating at 55° C. for on.- hour, and it may be kept with but little deterioration for long periods of time. Ambo- ceptor differs from complement in being very highly specific. An immune body developed by the injection of the red cells of a rabbit, for instance, will not unite with the red cells of any other animal. The comple- ment of normal serum, on the other hand, will activate many different amboceptors. These antibodies appear in the serum usually within from five to ten days after experimental or accidental infection, and form one of the strongest defences that the body is able to present against an infection. Almost all animal cells are able to stimulate the body to the production of ambocep- tors. In some instances experimenters have been able, by the injection of amboceptor, to stimulate the pro- duction of antiamboceptor, but the results have not been constant and there is still some doubt as to the accuracy of this explanation of the results obtained. The chief importance of the immune bodies is the part they play in the recovery of an animal from an infection, but they can also be employed in the diagno- sis of disease and in the identification of unknown organisms. An immune serum should cause lysis of the bacteria which have acted the part of antigen if sufficient complement is present. Therefore if either the bacterium or the serum is known, the other can be identified. For a discussion of the relation of the amboceptor to the general subject of immunity the reader is referred to the article on Immunity. Ralph G. Stillmax. Ambulances. — An ambulance is a vehicle specially designed for the transportation of sick or wounded. It owes its origin and general characteristics to the needs of civilized warfare. The growth of humane practices in the wars of the eighteenth century pro- duced an increasing demand for some method of carry- ing wounded both effective and merciful, and the French wars following the Revolution of 17;S9 brought the ambulance service along with all their other military innovations. An organized system for the transportation of wounded was first introduced by Baron Larrey, the French military surgeon, in the Army of the Rhine in 1792. Only slight improvement upon his system was made during the wars of the first half of the nine- teenth century, and it was not until the latter part of the Civil War that the ambulance obtained proper recognition and development in the introduction of a uniform system by act of Congress in March. iv. 1. The need for civil ambulances, though increasingly felt, was, of course, in these earlier day- less urgent, but shortly after the close of the war a modified sys- tem adapted for use in cities was recognized to be an important requirement of a well-organized hospital system; its adoption was repeatedly discussed in several of the hospitals of New York City, and in December, 1S69, the first service was established by the Commissioners of Charities and Corrections in Bellevue Hospital. Though crude and limited at first, the Bellevue service was rapidly improved and extended, and was soon copied by the other hospitals of New York. 237 Ambulances REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Important modifications in the army type were, of course, required in the adaptation of the ambulance to civil hospital work. The necessary changes were ap- parent and were quickly made; the civil could be lighter, and therefore faster, than the army vehicle on account of better thoroughfares; it would not be required to carry so many people, but for use in nar- row and crowded streets it must be able to turn in the arc of a small circle. Since the differentiation in the types of the two wagons in the more funda- mental particulars referred to, the evolution of the civil ambulance has been along lines chiefly of mechan- ical construction, and the very great substitution of mechanical for horse power since the introduction of motor vehicles. The type of horse drawn vehicle has remained essentially the same, but the restric- service is the most elaborate and enterprising, and will probably remain as the standard for this country. The eagerness of foreign medical authorities to accept American innovations effecting improved con- ditions of service, especially of a mechanical character has never been marked, and, in the case of the am- bulance system, has amounted almost to disin- clination. For one thing, the foreigner does not feel the constantly expressed desire of the American for rapidity of transit of all kinds. The hurry call f„ r fire and for accident relief does not seem to him bo urgent, and the ambulance is not to be found in his medical traditions. On the continent, ambulances fur the transportation of the injured have i„ until very recently an unknown quantity. Tl. of caring for the injured was and is in many cities Fig. SI. — Horse Ambulance. tions on weight being largely removed, the motor ambulances are, as a rule, much larger, more comfor- table and better protected from the weather. The advantages of an ambulance system com- mended themselves to the hospital authorities of every city of consequence in the United States, and ambulances were introduced as fast as means per- mitted or the conditions of each case required. The New York system has remained the most extensive and elaborate. In many of the smaller American cities where the number of hospitals is small, ambulances are few and are used chiefly for sick cases; their emergency use is restricted to a small area surround- ing the hospital. Accident cases in other parts of the city are attended to by the police patrol, which still performs in a rudimentary way the functions of an ambulance service proper. It is not so easy to understand why this use of patrols should survive, as it does, in many large cities, although there are unquestionably abuses of the ambulance system (hereafter touched upon) which are avoided when the duty is performed by the police. The New York 238 carried on by voluntary societies established for the purpose which maintained small stations in dif- ferent parts of a city where stretchers, splints, an' 1 . paraphernalia for first aid to the injured could be found. Delivery wagons requisitioned for the exigency and police patrol wagons were used to convej thi injured to hospitals. The ambulances, and they were often of a very primitive kind, were used only for the transportation of the sick. Within recent yea ever, there has been a marked change of attitude ail ambulances are now to be found in almost all *>f the large cities of Europe. They are still chiefly for the transportation of the sick, but are being used more and more for accident cases. They are admirably constructed and equipped. A trained attendant, nol a medical man, is carried. The conception of the duty of the hospital differs in Europe and America The European hospital considers it sufficient to pi vide proper transportation, the American hi considers it necessary to provide skilled treatment as Automobile ambulances here and abroad have REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Vliililll.ini < . ijgely taken the place of horse drawn ambulances, It have not entirely displaced them. Automobiles I vc not yet reached such a state of perfection that i v are absolutely reliable, especially during inclem- i winter weather with streets blocked with ice : I snow. The number of horse ambulances Still ', ployed is, therefore, large. liicyele ambulances have been tried in some places i li but little success. \ll horse ambulanees are so nearly alike that one , description will coverall their salient features. ; ,. enclosed body of the vehicle is from eight to ie feet long and from three to three and one-half I I wide. As lightness is an important element, it is ! ill of as light material as is compatible with thorough ength. The roof is supported by uprights, a hood i. ding over the driver's seat, and only a short i.incc is boarded in on the sides, the front and rear ug open. In cold or stormy weather all but the circumstances or the conditions of the streets require. The average weight, of such a vehicle is from twelve hundred to fourteen hundred pounds. The wheels are made with solid rubber I ires, which are as satis- factory and far more durable than the pneumatic tires that were in vogue for a short time. A large foot gong in front of the dashboard, or under it, can be operated by the driver. The most satisfactory situation for the stable is within the limits of the hospital, but in a separate building. By this adjustment the inevitable noise and odor are minimized, and the ambulance is still within close call. The interior arrangement of I he stable need not differ from that, of any private one. There should be one more horse than the number of ambulances in service, in case of accident or disease and to meet any emergency. One stall is kept for the horse on call, where he stands with his bridle in place, only the bit requiring to be inserted. The Fig. S2. — Ambulance Showing Movable Bed. ar can be closed in by leather or rubber curtains, ie patient lies on a movable bed covered with leather, id this runs on a track, and is so held by inverted imps that it will still remain horizontal when drawn it to its full length. A stretcher lies on this bed. lie surgeon sits at the rear on a transverse seat, -a over the tail-piece, so arranged that it can by ised perpendicularly and clasped out of the way lien the tail-piece is let down for the entrance or cit of the patient. A step behind assists the sur- -on to his seat, and there are straps to which he ay-hold. Under the driver's seat, in front, is room ir splints and other appliances, and the longer ilints are suspended by straps from the roof. A ntern is clamped inside, and two red lights on the de indicate to other drivers the ambulance's right way. The fore wheels can be cramped under the ire part of the vehicle, which can thus turn in the lortest possible space. Usually drawn by one horse, may of course be changed to a double rig whenever harness is patterned after that used by fire depart- ments, and hangs suspended over the shafts ready to be lowered; then the collar is clasped, one or two straps are buckled, and in a moment or two the trained horse is under way. Calls are sent to the stable from the office by telephone or gong. There must be one more ambulance than the number run- ning, in order that repairs required by accidents and wear and tear may be made without a disabling of the service. So, also, an extra man is needed to take care of the stable, horses, and ambulances, and to act as a relief driver and stable watchman. His extra time may be employed in the doing of other necessary work around the institution. A conventional assortment of medical and surgical instruments, appliances, and supplies is always kept in each ambulance, and others are carried by the surgeon in a hand satchel. Among the former are the long thigh and body splints that are suspended under the roof, and the shorter splints that are kept 239 Ambulances REFERENCE HANDBOOK OF THE MEDICAL SCIENCES under the driver's seat, together with one or two pairs of handcuffs. In an iron rack, in the enclosed part, just back of the driver's seat, is kept an assort- ment of bandages and cotton, and in other racks variously situated are found stomach pump, antidotes for poisons, bottles of carron oil, etc. In the satchel the surgeon carries sterilized dressings and band- ages, the ordinary instruments of a pocket surgical set, catheters, hypodermic syringes and needles, cardiac stimulants, tourniquets, and chloroform. This enumeration includes the standard articles carried, and hospitals differ as to the selection only in minor details. The cost of a horse ambulance complete with rubber tires, etc., varies between $550 and $700. The cost of equipping an entire service must include the stable with its furnishings, horses, harness, and am- and gasoline ones are now in active operation ir all of the cities of this country. As indicated abov< they are larger and of more solid construction thai the horse ambulances. The sides are of wood 01 wood and glass and they frequently are closed behint by a door. The}' are generally lighted by electricity Their increased size, sufficient to accommodate twi patients in an emergency, allows of many minoi conveniences and greater comfort, although thi tial features are the same as those of the horsi lance. Electric ambulances have the advantage tha solid rubber tires may be used and the unpleasant dela-\ incident to a punctured tire is avoided. On theothei hand, the speed of these is much less and tin v la, the power to drive them through snow which wouli not prevent the passage of a gasoline ambulance But no hospital, until motor vehicles have reachei Fig. 83. — Electric Automobile Ambulance. bulance, and demands a large initial outlay. The expense of maintenance, however, is less than would appear at first glance, and becomes proportionately cheaper as the number of ambulances is increased. Items to be considered are: Running repairs on ambulances (annually about $50 to $100 each), feed and shoeing of horses, wages of men and their board and incidentals, cost of medical and surgical equip- ment, etc. In New York the annual expense, com- Euted from the figures of a number of different ospitals, of running an ambulance service on the basis of two ambulances constantly in use and one for extreme emergencies, is between $2, 100 and $3,000. In other localities the cost varies with price of feed and of wages. The first automobile ambulance was put in opera- tion in New York in 1900. It was at once so success- ful that others were rapidly introduced. Both electric 240 a greater state of perfection, could be sure of maintain- ing an uninterrupted service throughout the yeai without a horse ambulance for use in an emergency, especially in the north where winters are seven-. Besides its speed and size the advantages of the motor ambulance are that it requires less room, it does away with the noise and odors of a I stable, it is always ready, no harnessing is nee and it is less expensive when in actual operation. The disadvantages are the great initial cost and the expensive repairs, that more skilled and thi more expensive labor is required, and that meter vehicles alone cannot entirely be relied upon. Motor ambulances cost between $3,000 and $5,000. I cost for repairs and for tires cannot with any accuracy be predicted. Before the general introduction of telephone were usually sent to hospitals in New York City bj REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ambulances ■ tinging of a gong, as is now done by the Fire partment. It was also customary at one time ; an ambulance to go to every fire call. Since ephones have become so universal tliey alone are ierally used. The ambulance work is under the ' iervision of the Police Department, and every call [theoretically supposed to be sent by an officer, ictically, however, every reasonable < ■; 1 1 1 suit by ; civilian is answered. The Fire Department iomes an element in falling ambulances only when re is a large fire with much loss of life. In .such e following the alarm of fire which is rung in : niisl all hospitals having an ambulance service, all of three fours is rung to summon all available ibulances in the city; immediate response is made i the call service'; the police system is undoubtedly more economical. In some- cities public hospitals do all i Ih> accident work, the private hospitals running am- bulances only for sick cases. Sometimes then- are ambulance stables distributed about t hi' city \\ il In nit trained surgical attendants; these carry patients directly to the nearest public hospital; in other cases all calls are sent in to the hospital. The value of prompt transportation without skilful assistance on the one hand offsets the intelligent skill coupled with delay on t he Ot her. The most perfect but most extravagant method is the establishment of an ambulance service in private as well as in public hospitals, and the assignment to each hospital of a limited area so that, all parts of a city can be rapidly covered by intelligent workers. This ■aiiiaiias^ ■af^ Fig. S-t. — Automobile Ambulance. Cities differ considerably in the way in which their cidenl service is done. Sick cases are everywhere nulled in much the same way; patients who are too or too poor to be taken in carriages are conveyed ' ambulances. The accident work in certain cities done entirely by po'ice patrols. This system has me peculiar advantages; it is not imposed on norantly by civilians, or wilfully abused by the ■lice themselves; slight scalp wounds received by Irunk and disorderly" unfortunates do not so often fiipy the time of a hospital staff, and cases of pre- nded illness are more carefully investigated, to the lief of the temper of the hospital authorities, while ills in outlying sections far from a hospital can be iswered more readily and promptly. On the other ind, the patients are not handled so carefully or so .ilfuhy, and ignorance does in exceptional cases pro- loe very serious consequences. On the balance of lvantage, the individual benefits by the hospital Vol. I.— 16 entails much expense on private institutions, which may even be laboring under financial difficulties, but is another refinement in the method in which many of our cities look after the welfare of their inhabitants. This is the case in the city of New York, where the Board of Charities divides the city into districts and allots to each district a certain number of police precincts. The districts are so divided as each to con- tain a hospital maintaining an ambulance service, and the jurisdiction of each hospital within the limits of its own district is complete. In all cities cases of contagious disease are trans- ferred to reception and contagious hospitals; this is generally done by special vehicles, old city ambu- lances altered into closed vehicles. There are in many of the cities ambulances operated by private individuals for the purpose of transferring patients in as inconspicuous a way as possible; these are built to represent an ordinary vehicle externally, 241 Ambulances REFERENCE HANDBOOK OF THE MEDICAL SCIENCES with a stretcher arrangement within like that of the usual ambulance. The varieties are numerous, and that one is best which least attracts attention. That ambulance services are imposed upon there can be no doubt; unfortunately there seems to be no remedy for the evil. The imposition is sometimes effected through ignorance, sometimes through design. The convenient and efficient practice of calling ambu- lances by telephone increases the opportunity for mischief. To the hysterical layman every attack of syncope means apoplexy, and every abrasion of the scalp a fractured skull. When these or kindred things come to his attention, he immediately sends in a "hurry call" by the nearest telephone, often Fig. So. — Interior of an Automobile Ambulance, with bed drawn out to receive a patient. without the knowledge or desire of the patient; when it is answered with all possible speed, the surgeon finds that the patient has gone home or refuses treatment. By ambulances, also, ready means is afforded to the policeman to dispose of his obstreperous and slightly battered alcoholic charges, and when no evidence of injury is apparent the sur- geon is solemnly told that the patient was comatose when the call was sent. A hospital that does not leave anything to the discretion of the surgeon, but insists on all cases being brought in, unless the pa- tient refuses, of course suffers most in this way. No remedy that will throw out all improper calls and answer all the worthy ones can be devised, and, as in the fire service, much time and money are sacrificed in order that no single case requiring attention shall be neglected. The position of ambulance surgeon is usually filled by internes or by physicians specially appointed for the purpose, or by students nearing the completion of their medical school course. There can be no doubt of the inadvisability of allowing medical stu- dents to occupy so important a position. Most cases require simple treatment, but exceptional circum- stances arise, and one untrained to meet them is little better than a layman. Such training as a service requires can be readily and thoroughly acquired in an emergency ward, under competent supervision, and as either of the first two methods brings every benefit to the patient, the choice must fall upon the one which better meets the requirements of the service without affecting the administration of the hospital as a whole. A very active ambulance service is too much of a drain upon the strength of a man busy with additional work; on the other hand such a service is but a slight inducement to a capable man, unless, as is seldom the case, it offers chance of future advancement. The question is open, and is decided in each case by existing conditions. John Howland. Ameba. — See Amoeba. Amelie=les=Bains. — These baths, situated in the extreme southwestern part of France, in the district of the Pyrenees, are said to be " the best baths in Europe where rheumatism can be safely treated in winter." _ The village of Am^lie-les-Bains, situated in the midst of pine trees, has a population of a!- 1.200, and is twenty-three hours by rail from Paris. The winter climate is dry, clear, and mild, and possesses some of the characteristics of a mount atmosphere. The average number of sunny d during the three winter months is sixty-two; cloudy, seventeen; and rainy, eleven. (C. B. Black. "South of France," 1905.) The mean temperature of Jan- uary is 45° F. ; of February, 47° F.; and of March, 53° F. " During the day, in the sun, the temperature rises considerably above these figures, but during the night and morning, especially in January, it falls con- siderably below them. Amelie is sheltered for the most part from the ci northwest wind which sweeps over the plain of Roussillon. The summer is hot, but the autumn i cool, and the air possesses the tonic quality of thai of the mountains and is not so relaxing as that atPau. The scenery is very attractive and there are many pleasant walks with fine views. The river Tech runs through the town, on the left side of which is the sunny and sheltered promenade called the "Petite Provence," a favorite winter walk. The springs are of the class of the hot sulphuron- waters similar to those of Aix-les-Bains; they contain the carbonate, sulphate, chloride, and silicate of sodium with a trace of carbonate of iron and calcium and free nitrogen. The temperature is from 90° to 148° F. As with other warm sulphur springs, these wat> -• are of value in chronic rheumatism in its various forms; chronic catarrhal affections of the respiratory organs; glandular tuberculosis; neuralgia; chronic skin diseases, such as eczema, prurigo; syphilis; uterine diseases, and certain bladder and kidney affections. As has been before noted, AmeUie is said to be the best station in Europe with hot sulphur springs, which, on account of its mild climate, can be utilized in winter. In the higher part of the village near the springs are the two hotels with baths: the hotel Them Romains, which is warmed by the hot water of the springs; and the hotel Thermes-Pujade, a part of which is warmed by the vapor of the springs over which it is located. In each case one does not have to go out of the hotel for the baths. Both hotels are in grounds of their own, and have sheltered walks. Various kinds of baths are given similar to those at other spas. The water is also used for drinking. Not far from Am6lie-les- Bains are various othi r thermal sulphur water spas: Preste-les- Bains; \ ernet- les-Balns; Ax-les-Thermes, which is said to K largest supply of thermal sulphurous waters in Europe; and others. Edward 0. Otis. 242 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amenorrhea \menorrhea. By amenorrhea ia meant a sus- osion or cessation of the menstrual function in a , I, ,an who is not pregnant and who has not reached e "change of life, or the period at which menstrua- ■ n naturally erases. The term should not be em- ,ved to include eases in which menstrual blood slides from the uterine mucous membrane r from that of the oviducts, since we accept the ictrine that the Fallopian tubes take part in the i.-t ion), but is prevented from making its appearance illy by some malformation, such as an im- rforate hymen. It should be borne in mind that i hea is not in itself a disease, but simply a re- It of some morbid condition affecting either the at large or some part of the genital apparatus. igical amenorrhea is that which exists prior to iberty, during a normal period of gestation, and equent to the establishment of the menopause. Causes. — There is scarcely any derangement of the neral health, especially if of a serious nature and in its course, that is not prone to prove at ist the predisposing cause of amenorrhea. Usually, T, these deviations from health affect either e function of hematosis, the general nutrition of the ■ iy, or the normal action of the nervous system, and o, or all three, of these disturbances may be unbined. Moreover, it may be said that defective ■ -mitosis is itself a nutritive disorder, and that all regularities of nutrition may take their origin in I nervous action. All this is true, but the actical utility of these distinctions remains doubtful, rertheless. Of the particular diseases that give se to amenorrhea, the most noticeable are pulmonary iberculosis and chlorosis. In both instances, the ispension of menstruation seems to be a conserva- ve effort on the part of nature to spare the system cry unnecessary tax, and this consideration alone ight to be enough to teach us that it is not the istablishment of the menstrual flow that we should m at, but rather the restoration of the general lalth. It has been doubted by good observers whether it is '^ible for a woman in perfect health to suffer from aenorrhea, and there is much to sustain this position; H it is certain, nevertheless, that in many cases the ipairment of the general health goes on for a long ^riod without producing amenorrhea, until, finally, une additional factor comes into play, and may uly be looked upon as the exciting cause of the isorder. Among these exciting causes we may •ckon almost all pelvic diseases, the functional ■rturbation consequent on exposure to cold during a icnstrual period, emotional shocks, and traumatic ijuries. Amenorrhea may be an indication of imperfect evelopment of the internal generative organs. This not infrequently the cause of late appearance of liberty, at eighteen to twenty years of age, the terus being a small infantile organ. Of course, ingenital absence of the organs of generation will be ccompanied by complete amenorrhea and even by n absence of the menstrual molimina. A curious irm of temporary amenorrhea, undoubtedly hemat- genous in nature, is that noted in young immigrants ito a country. For from six months to a year or more 'iere may frequently be noted in these young girls a >>tal suppression of menstruation, without any of lie symptoms of anemia or chlorosis. Certain mental iseases, especially those of the melancholic type, ■ ill be attended by varying periods of menstrual impression; and certain of the neuroses (chorea aajor, epilepsy) show the same peculiarity. A arge uterine tumor (fibroma or myoma), while ;enerally causing menstrual anomalies in the form of lysmenorrhea, monorrhagia, and metrorrhagia, may iccasionally cause complete amenorrhea, and in uch cases the diagnosis from pregnancy becomes xceedingly difficult or even impossible until after the normal duration of gestation has passed. Ovar- ian cystomata, on the contrary, an- not infrequently accompanied by absence of menstruation probably because of the anemia which is present in these eases in their advanced stage. Doubt has been east upon the doctrine that the menstrual function is dominated by the ovaries, but it cannot be said that the doctrine lias been over- thrown, and we have, therefore, to distinguish, for purposes both of diagnosis and of prognosis, between amenorrhea which is and thai which is not due to failure on the part of the ovaries. In other word . concerning ourselves only with the mechanism, and leaving ultimate causes out of account for the t inn- being, we have to distinguish between uterine and ovarian amenorrhea. Practically, the only guide we have to a failure of that ovarian action which should serve to stimulate the menstrual flow, is the absence of the menstrual molimen — the ensemble of symp- toms usually attendant upon the flow, including a sense of weight and pain in the pelvis, and in some eases pain, tenderness, and swelling of the breasts, with or without the various reflex disturbances that sometimes attend the menstrual effort. The uterine variety is to be recognized by the state of the uterus, which will commonly be found to be one of atrophy (including the so-called " superinvolu- tion") or of impeded circulation due to the contraction of old inflammatory exudates. Diagnosis. — Amenorrhea, as it is here defined, requires to be diagnosed only from retention of the menses and from the physiological suspension due to pregnancy. The diagnosis will necessarily rest upon a physical examination, and for the details the reader is referred to the articles on Pregnancy and on Menses, Retention of. Prognosis. — The question of our ability to restore the menstrual function is to be answered wholly in the light of the causes on which its suspension is found to depend. Grave constitutional diseases, such as pul- monary tuberculosis, render the treatment in that direction not very promising, while the cure of any less serious fundamental disorder may^ on the other hand, be reasonably expected to be followed by the re- establishment of menstruation. As regards the local conditions, atrophy of the uterus and functional inactivity of the ovaries must give rise to an un- favorable prognosis, although temporary benefit may be produced by treatment in some instances. The prospect is better in the case of old inflammatory disease within the pelvis, for such affections are often amenable to treatment. In general, the causes will be found to be remediable, and, therefore, the prognosis favorable. Treatment. — The patient should be made to understand, at the outset, that her courses will come on when her health has been reestablished, provided no obvious anatomical defect exists, which can be determined only by a careful physical exploration. Another caution needs to be given. Women who know or suspect themselves to be pregnant, fre- quently consult a physician in the hope that, in the attempt to bring on menstruation, he will really succeed in causing abortion. Whoever, under such circumstances, prescribes any measure, no matter how innocent, with the understood purpose of in- ducing the menstrual flow, is liable to have un- pleasant charges brought against him in case abortion actually does take place, even as the result of some interference with which he had no connection. When called upon to undertake the treatment of a case of suppressed menstruation, it is prudent, therefore, for the physician to satisfy himself that pregnancy does not exist, and, in case of doubt, to decline the management of the case unless he can protect himself in some way, as by insisting that some trustworthy person be made acquainted with the facts at the start. 243 Amenorrhea REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Having undertaken the management of a case in which treatment is sought for on account of amenor- rhea, the physician should make a systematic in- quiry into the patient's state of health, and whatever deviation from the normal standard is found should be made the subject of treatment. For the details of such treatment, the reader is referred to the articles devoted to the various diseases that may be found. But, while insisting upon the general futility of measures addressed to the organs concerned in the menstrual function, without first attending to the general health, it must be admitted, nevertheless, that in a very limited number of cases stimulation of those organs may be resorted to with some chance of success when no other indication can be made out; and. moreover, that, in cases in which there are other indications at first, there often comes a time when the result aimed at may be hastened by measures that operate directly upon the pelvic organs. There are but few therapeutic procedures that have a direct and unequivocal influence upon the function of menstruation, and, in so far as they tend to relieve amenorrhea, those few act as local stimu- lants. The so-called emmenagogues are not much to be depended upon, although we may admit that aloetics and chalybeates tend to produce a pelvic congestion favorable to heightened functional ac- tivity of the sexual organs. Tins is also true of sink remedies as apiolin and oxalic acid, which in suitable cases and in suitable doses will cause sufficient pelvic congestion to establish the menstrual flow. Their use, however, in the absence of other indications than the mere failure of the menstrual flow, is not to be recommended, although, if employed in conformity with such indications, they undoubtedly exert a certain influence. The preparations of manganese have been recom- mended by Ringer and Murrell. One-grain pills of potassium permanganate may be administered, be- ginning with one pill three times a clay, and increasing to two four times a clay. The use of the drug should be begun three or four days before, the time at which a menstruation should take place, and be continued, if the flow does not come on, until the time for the next period. It should be kept up also during the flow. Both sodium manganate and manganese binoxide are said to be equally effective, and it is stated that manganese acts as well with the plethoric as with the anemic. The manganese treatment has not, on the whole, justified the expectations with which its em- ployment was begun. Oxalic acid in doses of one- eighth to one-quarter of a grain three times daily, com- bined with lemon juice or citric acid, may be tried advantageously in certain cases. There are several other drugs that have more or less repute in the treatment of amenorrhea. Among them is apiol or apiolin, which is said to act best in cases in which whatever flow there may be is ill- smelling. From eight to ten minims should be given daily during the week preceding the day for menstruation to begin, and fifteen minims on the morning of that day. Cimicifuga has been thought serviceable in cases of delayed or arrested menstrua- tion. Senecio vulgaris has been recommended in cases unaccompanied by pelvic lesions. In the ovar- ian variety of amenorrhea, a preparation made from the expressed juice of the fresh ovaries of healthy young animals, has been used with success. Aloes undoubtedly aids the action of the other so-called emmenagogues, and should be employed if there is constipation. Electricity was formerly used more frequently as a provocative of menstruation than any other agent. Good effects were thought to have been produced by either the galvanic or the induced current. The use of electricity for this purpose has, however, largely fallen into disfavor. If used at all, galvanism is more to be relied on for increasing the blood-supply of the 244 uterus, while faradization may be useful to intensify and precipitate the hemorrhagic effort. To ac- complish the latter purpose, the application ou^ht to be made at a time when the degenerative changes in the endometrium have advanced to such a degree that heightened blood-pressure, aided by muscular action, may operate at the greatest advantage producing rupture of tin' capillaries. This condition can be judged to be present only when there are symptoms of ovulation, or when the amenorrhea is ,,f such recent date that the time for a menstrual Bom to fall due is accurately known. In the galvanism, it will generally be prudent to place both electrodes on the external surface, unless the current is quite weak and the sitting a short one; aiming however, to pass the current directly through the uterus. When the faradic current is' employed, or the other hand, one electrode should be applied within the vagina, or even within the canal of the cervix. Milder measures than the use of electricity will often succeed, especially when there is not" com- plete absence of the flow, but scantiness and lack of color of the discharge. Among these measures, refrigeration of that portion of the spinal region cor- responding to the motor center of the uterus is of greal value. The skin over the junction of the dorsal with the lumbar vertebras may be sprayed with ether but not frozen, three or four times a day, for five minutes at a time, or ice-water compresses may be applied. These means are supposed to exert their effect by depressing the activity of the vasomotor nerves. They are to be used only at the time when a menstrual flow is due. In the interim, an auxiliary measure of some value consists in the use of a very brief cold hip-bath every night. W. A. Newman Dokla.nd. American Medical Association. — The American Medical Association owes its existence largely to a widespread demand which had prevailed in the British Colonies of North America long before the Revolution- ary War for a uniform and withal a more thorough education, for those intending to practise medii The first clinical lecturer on medicine in this country seems to have been Dr. Thomas Bond, who gave instruction to medical students in the first permanent hospital in North America, which opened in Philadelphia in 1752. This led to the establishment of the Medical Department of the Uni- versity of Pennsylvania which opened its doors to students in 1765. Seventeen years later thi medical school in the United States was establisl in connection with Harvard University. These v. the only permanent medical schools in this country that were in operation prior to 1800. This was nearly 200 years after the settlement of the country. When, however, the great distances, the limited re- sources of the people, the sparse settlements, and the difficulties of transportation in America before the Revolution are considered, there is little wonder perhaps at, the slow development of American medical schools. In 1760, the General Assembly of New York, and in 1772, the governing body of the Colony of .V. Jersey, had "passed measures for restricting medical practice by requiring an examination in 'physick surgery."' In 1S27, the Medical Society of 'the State of Vermont issued an invitation to the medical socie- ties and ''Institutions," of the States of Maine, \< Hampshire, Vermont, Massachusetts, Rhode Island, Connecticut, and New York, to a conference which was held at Northampton, Mass., June 21, 1827. The object of the convention was solely the improve- ment and standardization of medical education in the United States. A set of regulations was adopted, requiring a four years' course of study for the degree REFERENCE HANDBOOK OF THE MEDICAL SCIENCES American Medical Association doctor of medicine, as well as a good preliminary nation, evidence of good moral character and the tainmenl of the age of twenty-one years by the iplicanl for the degree. [,, the following year (1828) the Medical Society of e stai<' of New York, recommended " the calling of National Convention to consist of a delegate from tlir regular medical colleges ami the State societies to meet in Philadelphia for tin' of suggesting a more uniform system of ■ilical education than now prevails." movements seem to have accomplished little, cept to direct attention to the unsatisfactory itus of medical education in America in the early rt of the nineteenth century. The United States ■re growing fast in wealth and population and 1830 and 1S45, the number of medical colleges lan doubled. These institutions wore without y supervision and had full power to confer the de- doctor of medicine, and inasmuch as many , had been started with insufficient equipment d with little or no endowment, the eagerness to indents was extreme, and the tendency to lie courses of study leading to the doctor's <- short and easy as possible, seemed to be lie. The annual courses of lectures had been ly shortened to sixteen weeks and in some ,s, to thirteen. Two of these courses, without any or laboratory advantages, and a year or two more or less nominal study with a preceptor, were teemed sufficient to qualify a student to receive the • degree and to practise medicine anywhere in United States. In 1835, the .Medical College of Georgia proposed call a convention of delegates from all the medical lieges of the Union to take these matters under ration. In 1S39, the Medical Society of the ate of New York took the matter up again at its mual meeting. After a full discussion of the question medical education in the United States, a resolu- - passed by a large majority of those present, daring that "the business of teaching should be parated as far as possible, from the privilege of anting diplomas." An invitation was sent to all e medical societies and medical colleges in the untry to send delegates to a convention to be held Philadelphia in 1S40. This movement, however, d not elicit enough enthusiasm to bring about the ■sired result, and the matter was dropped temporar- -. But the subject would not down, and was again ought up in the medical society of the State of r\v York in 1S44, and was vigorously pushed by athan Smith Davis, a young practitioner and a new to the State Society from Broome County, - made chairman of a committee to investigate e entire question and report upon it at the next an- uil meeting. This committee having communicated ith practically every county medical society in the ate of New York, had aroused much interest in the i of medical education by the time of the next inual meeting of the Society, when, after an arduous bate, it was determined to call a national conven- iq in New York City in May, 1846. The medical 'ess quite generally lent its aid in pushing this oject and Dr. Ticknor, the President of the Medical iciety of the State of Connecticut, proposed that te convention should organize itself into a National 1 dical Society. The idea of a permanent national ■ ii-ty was enthusiastically embraced by Dr. Davis, ho exploited it freely in the medical press. The delegates met in the hall of the Medical De- I of the University of New York on May 5, ^16. Of 119 delegates appointed by the various icieties and medical schools throughout the nion, about 100 were present, and took part in the liberations. They represented sixteen of the tales of the Union, an especially large delegation -'ing present from the societies and medical schools "i Philadelphia. The following propositions wen- laid before the convention: " 1. That it is expedient for the medical profession of the United States to institute a National Medical Association. "2. That it is desirable that a uniform and elevated standard of requirements for the degree of Doctor of Medicine should be adopted by all the medical schools in the United States. "3. That it is desirable that young men, before being received as students of medicine, should have acquired a suitable preliminary education. " 1. That it is expedient that the medical profession in the United States should be governed by the same code "f ethics." Each of these propositions was referred to a com- mittee of seven, with instructions to report at a con- vention to be held in the City of Philadelphia in May, 1847. A committee was appointed to invite every regularly organized medical society and chartered medical school in the United States "to send delegates to the Philadelphia meeting. A resolution was adopted setting forth that " the union of the business of teaching and licensing in the same hands is wrong in principle, and liable to great abuse in practice"; and recommending that "all licenses to practise medicine should be conferred by a single board of medical examiners in each State." This also was referred to a committee to be reported upon at the meeting in Philadelphia. Committees were also appointed to report at the same time and place, upon the best method of securing registration of births, marriages, and deaths throughout the United States, and upon the adoption of a proper and uniform nomenclature of diseases and causes of death. In Ma}', 1S47, the convention met in Philadelphia. There were present about 250 delegates, representing not less than forty medical societies and twenty- eight medical colleges, which were the organized medi- cal institutions of twenty-two of the twenty-six States of the American Union. The reports of the various committees appointed at the previous meet- ing were read and after careful consideration, were, in the main, adopted. The convention resolved itself into the American Medical Association, adopted a constitution and by-laws and a code of ethics, and adjourned to meet in Baltimore the following year. The large share which the Medical Society of the State of New York took in initiating and carrying out the work that had resulted in the formation of this Association shows that the Empire State was the cradle of the movement. Membership. — The plan of organization provided that "members of the American Medical Association, should be either delegates from local institutions i State, or county, or town medical societies, medical colleges and hospitals, lunatic asylums, and other permanently organized medical institutions, in good standing"), or members by invitation, or permanent members. Thus there were created three classes of members, of which the delegates constituted the bulk, and the most important part. Each delegate was appointed for one year. The basis of representation was one delegate for every ten regular resident members of every regularly organized medical society. Two delegates for even- regularly constituted and chartered school of medicine, two for every hospital containing 100 beds or more, and one for all permanently organized medical institutions of good standing, not included in the above summary. In order to admit of representations from portions of the United States not otherwise represented, provision was made for members by invitation. If a physician from a section of the country in which no medical institution of any sort existed, attended an annual session, the association could elect him a member by invitation for that session only. He thus became an unofficial delegate for a section of the country that 245 American Medical Association REFERENCE HANDBOOK OF THE MEDICAL SCIENCES would otherwise have been without representation. Any member belonging to one of these two classes, after his appointed service, and such other persons as the association might select by unanimous vote, might be made permanent members. These were entitled to attend the meetings and to participate in the busi- ness of the association, but had no right to vote. In 1850, at the third annual session of the associa- tion, a resolution was offered that members by invi- tation should become such only after a committee had passed upon their eligibility. In the following year (1S51) a minority report from the committee on amendments to the constitution, allowing the per- manent members to vote, was defeated by a large majority. Thus it can be seen that from its earliest history, the association established the principle which has been adhered to up to the present time, that it is essentially a representative body exercising powers delegated to it by State and county medical socii i ies and medical institutions distributed over the entire country. No further change of any importance was made in the matter of membership in the American Medical Association, until the session of 1S69 at New Orleans, at which an amendment was adopted that a continu- ous membership in a county or State society, where one existed, was essential for membership in the National Association; and that without a continuous membership in such local or State society, no one could retain his membership in the American Medical Association. This applied to all classes of members. In 1874, at the twenty-fifth annual session at Detroit, a provision was adopted limiting the dele- gates to those selected from the members of per- manently organized State societies, and such county and district medical societies as were duly represented in their State societies, and from the medical de- partments of the Army and Navy of the United States. The United States Marine-Hospital Service was subsequently admitted to the same representation as that of the Army and Navy. In 1881, a fourth class of members was provided for, viz., "members by application." It was voted that members of State or county societies, certified to be in good standing by the president and secretary of such a society, might become members of the Ameri- can Medical Association "by application." They were entitled to attend the annual sessions, and to receive the journal of the association, but had no right to vote. These provisions regarding member- ship remained in force until the reorganization in 1901, when the only societies recognized as having the right to send delegates (i.e. to be represented in the newly formed House of Delegates) were the State societies. Primarily only delegates could become members, and up to the time of the proposed establishment of the Journal (1881) the only means of becoming a member was to attend an annual session of the Ameri- can Medical Association, either as a delegate, or a member by invitation. Membership by application was devised to allow members of county and State societies to become members of the American Medical Association (and to receive the Journal) without attendance upon an annual session of the Association, and without having been elected delegates to such a session. The basis of representation was changed from one delegate to ten members of a constituent society, to one delegate to every 500 members of a State society. At the former rate there would have been 6,000 delegates at the annual meeting in 1901; since the constituent State societies contained an aggregate of 60,000 members, or about half of the entire num- ber of physicians in the country at that time. The House of Delegates is now limited by the titution to 150 members, of which seventeen represent the sections of the Association and the public services. When the membership in the State societies shall have increased so that the aggregate of delegates shall exceed 150, on the present basis of rep- resentation, this will be raised, so that the total num- ber of delegates shall not at any time exceed the present total. At the second meeting of the Association in Balti- more in 1848, the registration was 266, representing societies and medical institutions in twenty-one States and the District of Columbia. The Presidi Dr. Nathaniel Chapman of Pennsylvania, decline election and advocated the plan of rotation in office, a rule which so far as the office of president and th.i-i- of the vice-presidents are concerned, has been rigidly adhered to ever since. The scientific and literary work of the Association was presented in the form of reports of the com- mittees which had been appointed for this purpose at the original meeting. To the report of the conim on surgery were appended three papers on anest agents in surgical practice. These papers led to an interesting discussion in which Dr. J. C. Warren of Boston, Professor of Surgery in the Harvard Univer- sity Medical School, who had but recently performed the first major surgical operation in the world upon a patient who had been rendered insensible by the in- halation of ether, took an active part. Dr. Olivet Wendell Holmes, Professor of Anatomy in the Harvard Medical School, presented the report on Medical Literature, and Dr. Alexander H. Stevens of Ne York, the newly elected President, and also at that time President of the College of Physicians and Surgeons of New York, presented the report on Medical Education. Dr. Holmes criticized with severity the rather un- satisfactory character of the current medical litera- ture and exhorted the members of the Association to produce original medical brochures and text-books, instead of contenting themselves with editing thos foreign authorship. A communication was received from the medical department of the National Institute in referent the sanitary condition of the United States, stating that they had appointed a committee to take matter up and urging the cooperation of the Associa- tion. This request was acceded to and a cooperating committee appointed. Dr. T. O. Edwards, then a member of Congress from Ohio, presented a memorial to the Association relating to the adulteration of imported drugs, and urging Congress to take action to prevent this, and to require an inspection of all im- ported drugs and medicines. Another report was presented demanding a careful study and report upon the medicinal properties of all the indigenous plants in the United State*. Committees were appointed to visit the British and Provincial Medical and Surgical Associations. Considering all that had been accomplished in the first year of its existence, the remarks of its president on taking the chair, do not seem extravagant. II expressed the hope that the Association might "ex- hibit in a new form to our brethren in Europe, the easy adaptation of our institutions to the great eni promoting the happiness of mankind." The State Societies and the Medical Colleges. — During the period intervening between the sitting of the con- vention in Philadelphia and the next annual meeting in Baltimore (1846-47), new State societies ' organized in South Carolina, Alabama, and Pennsyl- vania and the already existing State societie Georgia, Mississippi, Tennessee, Ohio, and Wisconsin were aroused to renewed vigor and efficiency. In all of these societies and in others in the New and Middle States, resolutions were adopted appro' the proceedings of the National Convention, es cially those relating to medical education, ommendation that the course of study in the medical 246 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES American Medical A SSOI hi t litu ioo |s I"' increased to six months in each year, met I, general approval, except that the delegates from the medical schools objected, fearing that the i ,uls in which they were interested would lose However, the University of Pennsylvania end its course-; of lectures to six months, and ■ College of Physicians and Surgeons in New York, ■ oldest and most influential of the medical schools i the metropolis, extended its lecture period to five While most of the other medical schools ■d themselves with adding to their curricula o to four weeks of optional preliminary ion, \i the annual meeting in 1N53, thirty States and (ritories were represented by delegates, as well as Hi of Columbia, the Army and Navy of the lited States, the American Medical Society of id one member was present by invitation "from and one from Canada West. The whole ■nber of members in attendance was 573, and the umber of institutions and societies represented Previous to the organization of the National Associa- ' ii' medical societies had been formed in about jlf of the States of the Union. But a large proportion had practically ceased an active existence. en State societies and eleven local ones were tited in the National Convention held in 1846. Philadephia, in the following year sixteen State were represented, all that were known to be active existence in the United States at that time. ght years after the organization of the Association, enty-six State societies were represented in its ;nual meeting, together with delegates from the ietv of Minnesota Territory and that of the 1 erokee Nation, and from more than 100 county, ,-trict, and town societies. The Code of Ethics. — It is a noteworthy fact that ■ 're has been only one schism or split of any con- llerable consequence in the ranks of the American lical Association since its foundation, and that 1 'urred in the State of New York; which, as already iitcd out, is the State in which the Association illy had its origin. The quarrel was over the so-called code of ethics, lich like the theological tenets of former ages, led many prolonged and bitter controversies. It is ble in a limited space properly to consider the de of ethics in all its bearings. Suffice it to say at one section of this document, which all members the Association were obliged to subscribe to, for- ile consultation with any practitioner whose prac- e was based upon "an exclusive dogma." The dical society of the State of New York had long afed under a too strict interpretation of this pro- lition. and many of its members maintained that it is unjust and improper to refuse to consult with le- lly qualified practitioners, no matter whether they •re bound by an exclusive dogma, or not. Steps were ken to induce the National Association to modify code of ethics which had been preserved intact ice its original adoption in 1S47, but without avail, nally, at the annual meeting in February, 1882, the Ural Society of the State of New York adopted a le of ethics, or rather statement of principles, the effect that "the only ethical offenses for which '■y [the medical profession of the State of New York] um and promise to exercise the right of discipline " those comprehended under the commission of acts ■ worthy a, physician and a gentleman." At the meet- g of the National Association following this action, e Judicial Council ruled that the New York Society, iving adopted a revised code several provisions of iich were in conflict with the code of ethics of the ssociation.was not entitled to representation by dele- tes in the American Medical Association. There- ter for over twenty years the Medical Society of State of New York was not represented in the councils or scientific work of the .National Associa tion. The State, however, was not long without represen- tation, for in 1884 a number of physicians in New York, .who were willing to subscribe to the code of ethics of the American Medical Association and who wished to retain the right of membership in the Asso- ciation, established a new society entitled the New York State Medical Association. There were then three classes of pracl itioners in Now York State : those who believed in the old code, those win, had adopted the new code, and those who regarded all codes as unnecessary. When the American Medical Association was re- organized in 1901, it was hoped that some modifica- tion would be adopted in 1 lie cod,- of et hies, or in its enforcement, so that a union might lie brought about between the two medical societies in the State of New- York, and all their members might be eligible to membership in the National Association. The last named body, however, declined at that time to modify its code of ethics, and the union was postponed. However, the leading men in all three of these socie- ties were by this time striving for harmony, and finally in 1903, the National Association abrogated the compulsory clause in its code of ethics which had made all the trouble, and adopted in place of the old code certain"principles of medical ethics' which it pro- mulgated as "a suggestive and advisory document." There was then no longer any cause for dissension, and on January 1, 190(3, one hundred years after the establishment of the Medical Society of the State of New York, this society and the Medical Association of the State of New York, having overcome certain legal difficulties in their way, were amalgamated, and with much satisfaction and general good feeling, laid to rest forever the objectionable feature of the code of ethics. The Journal. — The history of the progress of the Association for the first thirty years of its existence, is not especially noteworthy. Gradual progress was made along the lines laid down by its founders. Two or three sessions were missed during the troub- lous times of the civil war. With these exceptions, however, not a year has passed in the sixty-seven years of the existence of the Association in which a meeting has not been held and more or less good scientific work done, as well as some effort made to bring about improvements in medical education for the enactment of better health and quarantine laws and the furtherance of many good objects which the founders of the Association had in mind. Still the Association lacked coherence, and it lacked funds. Its loose organization precluded almost any sustained and effective scientific or legis- lative work. Its means of communicating with its members were inadequate, and it was without power to discipline either its own members, or the profession at large. It was obvious that one potent means of accomplishing a stronger organization would be the establishment of a journal. Hence, as early as 1S52, it was proposed to start a journal. Again in 1870, Dr. Samuel D. Gross of Philadelphia offered a resolu- tion that the transactions be periodically published in a journal. This resolution was passed and then rescinded. In 18S0, Dr. Louis A. Say re of New York made a similar proposition to the society which was referred to a committee who after a careful investiga- tion, recommended that another committee be appointed to report in detail a plan for journalizing the transactions of the Association. Again the inde- fatigable N. S. Davis came to the fore and by his industry and perseverance secured pledges from 2,100 physicians to sustain the Journal. Dr. Davis became its editor and the first issue appeared in 1SS3. At that time the membership of the Association was about 2.000. The annual dues were .S3. 00 which were in many cases uncollectable. The financial 247 American Medical Association REFERENCE HANDBOOK OF THE MEDICAL SCIENCES outgo was between five and seven thousand dollars, the greater portion of which was spent in printing, binding, and distributing the annual volume of transactions. With the publication of the Journal, a new era in the life of the Association was begun. In fifteen years the edition of the Journal of the American Medical Association had risen, under the editorship first of Dr. Davis, then of Dr. John B. Hamilton, from 3,800 to 11,270. In 1S9S the present editor, Dr. George H. Simmons, took charge. The member- ship of the Association has now reached over 34,000 (about a quarter of all the physicians in the United States), forming a body about one-half as large again as that of the British Medical Association, which was started in 1S32, but which did not complete its present organization as the National Association of Great Britain until 1S56, about ten years subsequent to the establishment of the American Association. The cir- culation of the Journal has increased to nearly 54,000, including the membership list, and the assets of the Association have increased since 18S3, from a deficit on the Treasurer's books to over one-half a million dollars, of which, $100,000 represents interest-bearing invest- ments and over $350,000 represents real property, ma- chinery, furniture, and supplies. The gross revenue amounted last year in round numbers to over $459,000 and after all expenses covering insurance, deprecial inn of plant and machinery, etc., had been deducted, over $53,000 was added to the assets of the Association. Organization. — By the reorganization in 1901, as already stated, the American Medical Association was divided into a scientific and legislative body. The latter has already been described as the House of Delegates which does all the business of the Associa- tion including the election of the officers. The scientific work is done in fourteen sections covering every branch of medicine and surgery. From 3,000 to 6,000 members attend the annual meetings of the Association. The finances of the Association and the business management of the Journal and of the investments and the care of all the property, are in the power of the Board of Trustees. This consists of nine members, three going out of office yearly and being succeeded by new men, elected by the House of Delegates. The judicial council consists of five members (one elected each year) and the secretary of the Associa- tion. They look after and regulate all matters need- ing adjudication between members and between the American Medical Association and other medical societies, and harmonize the action of the diverse interests over which the Association lias supervision. There are besides, three permanent councils: 1. That on Health and Public Instruction, consisting of five members and the secretary of the Association. 2. That on Medical Education, consisting of five members and a secretary. 3. That on Pharmacy and Chemistry, consisting of fifteen members and a secretary. A brief review of the work of these councils will serve to outline some of the major activities of the Association since its reorganization in 1901. The council on Health and Public Instruction has conducted a Publicity Bureau and has sent informa- tion on matters affecting public and personal health to 5,000 newspapers and periodicals in the past year only six of which have declined to receive and make some use of the information. This is sent out in weekly bulletins, and covers practically the entire range of hygiene and preventive medicine. A sub- committee of this council has waged war against preventable blindness, with great success. The council also maintains a corps of healfh lecturers, at present consisting of 100 speakers, who will go any- where in the United States upon request, and address lay and professional audiences on matters of State and personal sanitation. 248 The council on Medical Education has finished its third complete report upon every medical teaching institution in the country. In the past five years fifty-six medical schools in the United States have closed their doors or merged themselves into other schools, evidently as a result of the publicity to which they have been exposed. All the medical schools in the United States are carefully classified in the Council's report, as good, fair, and poor. Of the 14:: schools now active in this country, nearly one-half are reported to be inadequately equipped, or defective in some important particulars. Fortunately, a college diploma no longer confers the right to practise medicine, inasmuch as the appointment of a 81 medical examining board has been secured in every State in the Union. Efforts are now being mad'' to equalize the requirements for license to prai throughout the country, and to elevate and improve the personnel of the State examining boards. Further- more, an effort is also being made to require at lea I one year's internship in a recognized hospital before a physician shall be licensed to practise. The work of the Council on Pharmacy and Chem- istry is almost too well known to require comment. They will examine and report upon any remedy, new or old, that is advertised to be useful in the treatment of disease. The amount of work that they have done in bringing to light frauds : deceptions in the drug and medicine business almost incredible. It is to be hoped that their efforts to establish standards of purity and reliability in the entire drug business, and even in that of handling and preparing food of all sorts, will be abundantly successful. Besides the Journal of the American Medical Association, the Board of Trustees have authorized the publication of two other periodicals, "The Archives of Internal Medicine" and the "American Journal of the Diseases of Children." The Associa- tion has also compiled and published a register of every physician in the United States and Canada, which is claimed to be complete and authoritative. It should not be forgotten that for over fifty years, the American Medical Association has struggled for a National Department of Public Health and is still bending its energies toward the establishment of that great boon to our common country. Of the great objects with which the founders of the Association charged themselves, all have bet accomplished, or are in fair way to be accomplish Like the statesmen who founded our government, and gave us our national constitution, the wise men who founded the American Medical Association "builded better than they knew." Richard Cole Newton. Ammoniacum. — Ammoniac. Gum Ammoniac. \ gum resin obtained from Dorema ammoniacum Don i lam. Umbellifera:). The ammoniac plant abounds in the deserts of Persia and Beloochistan. It is a stunt perennial herb two meters or more in height with a few coarse leaves at the base and a large terminal panicle of flowers. It grows from a large turnip-like root, which has a domestic use under the name " l J ">in- bay Sumbul." The milky juice exudes from punc- tures made by beetles, and concretes upon the often falling to the ground in irregularly rounded 01 ellipsoidal nodules or "tears" often nearly an inch in diameter, which constitute the drug of commerci In the best grades, these tears are dry and separate, but are sometimes soft and agglutinated. Tiny a brownish cream-colored externally, darkening namon brown with age, creamy white, or pure white within. They break with a conchoidal fracture, dis- closing a waxy, but shining surface. The odor is peculiar, rather disagreeable, but faint, excepting u masses or upon warming. The taste is bitter and REFERENCE IIWIMtiioK OF THE MEDICAL SCIENCES Ammonia and Ammonium Sails i her acrid. It is a difficult drug to powder, unle , v cold or very dry. When heated it softens, but , , s I,,, i melt. Alcohol dissolves about three-fourths , i. Water disintegrates it, and forma with it a milky , ulsion. Ammoniac consists of about seventy per cent, of ■ in, fifteen to eighteen per cent, of .soluble gum, anil Ki rest of insoluble gum, water, and from one-half i four per cent, of volatile oil. The latter does no! nil sulphur, and, therefore, is not similar to the of asafetida, which drug is much adulterated with moniac. Vminoniac is stimulant, expectorant, and antispas- IjidiC, but is scarcely used now internally. The dose ,., id to be 0.5 to 2 grams (gr. viij.-xxx.) thre ■ mes a day. An emulsion would be an eligible i although a tincture would probably contain all i is active in it. The principal preparation is uiac Plaster (Emplastrum Ammoniaci), made softening the ammoniac in diluted acetic acid, and iporating to a suitable extent. It is a stimulating : 1 rubefacient, sometimes blistering application, i ful as a mild counterirritant. One other species of Dorema, according to the i icographia," yields ammoniac. Bentham I Hooker include only two species in the genus. e ammoniac of Dioscorides and Pliny, and other i, nt writers, was obtained in Africa, and is a dif- lent article, namely, a gum resin obtained from ingitana Linn. It is rarely found in European i irkets. II. II. RUSBY. \mmonia and Ammonium Salts. — General Med- sai. Properties op Ammonium Compounds. — umonium compounds, as a class, are irritant, ally, to a degree greater than that shown by the .'■responding compounds of sodium, but less than : the case of compounds of potassium. They tend be of high diffusion power, and are therefore, len swallowed, quickly absorbed, and hence are c from the purgative tendency of the low diffusion Its of potassium, sodium, and magnesium. C'on- tutionally they tend to increase the force and [uency of the heart's action and to determine a e of arterial tension; to excite the respiratory nter in the medulla oblongata, causing fuller and ire frequent respirations, and to enhance reflex itability of the motor tract of the spinal cord — an limn i incut leading in poisonous dosage in animals tetanoid convulsions. General nutrition is not riously affected by therapeutic doses. In long- atinued excessive dosage the heart becomes feebled and the quality of the blood deteriorates, th marked impairment of the power of the hemo- ibin to fix oxygen. An important difference be- een the alkaline ammonium compounds and the [•responding potassium, sodium, and lithium eparations is that, whereas the latter carry their kalinity through the system generally and into the ■ine, no such effect follows the ingestion of the mnonium compounds. On the contrary, the idity of the urine tends rather to be enhanced under umonium medication. The explanation of this •culiarity among ammonium compounds is an sinned oxidation of the elements of the ammonium dicle, leading to the formation of nitric acid as one of ie products. By virtue of the properties described, umonium compounds furnish important medicines i restoring or sustaining flagging heart or lung tiou; for relieving dyspnea, and for opposing the tion of motor-paralyzing poisons. The Ammonium Compounds Used in Medicine. -These are ammonia, and the following ammonium ilts: salicylate, carbonate, acetate, chloride, bromide, dide, benzoate, and valerate. In the present "tide will be discussed the first three only; for the others see respectively Chlnriilcs, Bromides, Iodides, Benzoic Arid, Salicylic Aral. I aleric Acid. Ammonia. — Ammonia, NIL,, is used in medicine only in aqueous or alcoholic solution, as afforded by the following official preparations of the U. S. P.: Aqua Ammonia Fortior, Stronger Ammonia Water. This is an aqueous solution of ammonia, containing twenty-eight per cent., by weight, of the gas. It presents itself as a "colorless, transparent liquid, having an excessively pungent odor, a very acrid ami alkaline taste, and a strongly alkaline reaction. Specific gravity, 0.897 a! 25° C. (77°F.)." (U. S. P.) It is completely volatilized by the heat of a water bath. On bringing a glass rod, dipped into hydro- chloric acid, near the liquid, dense white fumes are evolved. From the volatility of its contained am- monia this preparation is directed to be kept in "partially filled strong glass-stoppered bottles, in a cool place." Aqua Ammonias, Ammonia Water. "An aqueous solution of ammonia, containing ten per cent., by weight, of gaseous ammonia." This weaker solution has the properties of the stronger, only not to so intense a degree. Its specific gravity is 0.958 at 25° C. (77° F.). It also should be kept cool, in glass- stoppered bottles, but the precaution to avoid filling the bottles completely is not here necessary. Dose, about itstxv. (1.0). Spirit us Ammonia;, Spirit of Ammonia. " An alco- holic solution of ammonia, containing ten percent., by weight, of the gas." This solution is prepared by subjecting stronger water of ammonia, in a still, to a gentle heat, and conducting the ammonia gas thereby volatilized to a receiver containing freshly distilled alcohol. The product is assayed and brought to standard strength by the addition of alcohol. Spirit of ammonia is a "colorless liquid, having a strong odor of ammonia, and a specific gravity of about 0.S0S at 25° C. (77° F.)." (U. S. P.) It should be kept in glass-stoppered bottles, in a cool place. Dose, about njixv. (1.0). Spiritus Ammonia: Aromaticus, Aromatic Spirit of Ammonia. This is a composite preparation, contain- ing, in 1,000 c.c., ammonium carbonate, 34 grams; ammonia water, 90 c.c; oil lemon, 10 c.c; oil of lavender flowers and oil of nutmeg, each, 1 c.c; alcohol, 700 c.c; and the rest distilled water. It is a "nearly colorless liquid when freshly prepared, but gradually acquiring a somewhat darker tint. It has a pungent ammoniacal odor and taste. Specific gravity, about 0.900 at 25° C. (77° F.)." (U. S. P.) Dose, about mrxxx (2.0). This spirit, like the other ammonia solutions, should be kept glass-stoppered, in a cool place. But in spite of this precaution, the fact obtains generally with ammoniacal solutions that they lose strength upon keeping, so that a sample a year or more old may be almost wholly without ammoniacal odor. Ammoniacal solutions are incom- patible with acids, acidulous salts, and many salts of the metals and earths; ammonia, however, does not decompose calcium salts, nor, except partially, those of magnesium. Ammonia is a powerful alkali, and in gaseous form is intolerably pungent, its fumes, if strong, exciting vigorous spasm of the larynx. In strong solution, it is intensely irritant. Either of the official ammonia waters or the simple spirit will, if of standard strength, excite severe irritation upon incautious inhalation of the fumes, and if applied to the skin upon cloths so covered as to prevent evaporation, will very speedily cause burning pain and redness, and, after a few minutes, blistering. Prolonged application may lead to ulcerative inflammation or gangrene. Internally, in proper dilution, ammoniacal solutions are locally alkaline so far as the contents of the stomach and bowels are concerned. Also, because of the pun- gency and volatility of ammonia, they tend to allay nausea and to expel flatus. Ammonia, being of 249 Ammonia and Ammonium Salts REFERENCE HANDBOOK OF THE MEDICAL SCIENCES high diffusion power, is readily absorbed, whether taken by swallowing or by inhalation, and then quickly but evanescently exerts the peculiar effects of the ammonium compounds upon the heart, respira- tion, and motor tract of the cord, as already set forth. Undiluted, the three first-named pharmaco- pu'ial ~ . 1 1 1 1 1 i < . 1 1 ^ i.f ammonia arc so irritant as prac- tically to be corrosive to the mucous membrane of the stomach and bowels. Large doses are, therefore, violently poisonous, capable of causing speedy death, with all the usual symptoms of corrosive irritation. In some cases death results in so short a time as a very few minutes, probably from suffocation through rapidly developed edema of the glottis. So small a quantity as about a teaspoonful and a half of a strong solution of ammonia, swallowed undiluted, has killed. Dangerous, and even fatal, poisoning has also resulted from inhalation of strong ammoniacal fumes. The therapeutic uses of ammoniacal solutions are local and general. Locally, according to strength of application, ammonia may be made to serve as a vesicant or rubefacient. To blister, a pledget of lint, steeped in a strong solution, is covered with a watch- glass or wooden pill box to prevent evaporation, and then directly applied. In such way the stronger water of the Pharmacopoeia has been used, but this solution is unnecessarily and, unless very carefully manipulated, dangerously strong. If employed, the application should be held in contact with the skin for only three or four minutes, or until the part is well reddened, and should then be removed and a hot poultice applied until the blister rises. It is safer to dilute the stronger water with one-half its volume of additional water. Ammonia is rarely selected as a blistering agent, unless the need for the blister is urgent, when the quickness with which ammonia acts makes it preferable to cantharides. For rubefacient purposes a clash of the stronger water is a very com- mon addition to composite liniments, and there is official in the U. S. P. Linimentum Ammonia, Ammo- nia Liniment, or, as it is sometimes called, volatile liniment. This preparation is made by mixing 350 c.c. of ammonia water (not the stronger water) with 50 c.c. of alcohol, 570 c.c. of cotton-seed oil, and 30 c.c. of oleic acid. An ammonia soap results, which partly dissolves and partly remains emulsified in the fluid, forming a white viscid mixture. The prepara- tion is saponaceous, yet possesses mildly the irritant qualities of ammonia, and makes a capital liniment for rubef action. Still a third local purpose of ammonia is to relieve the pain or itching of bites of insects. For this purpose a drop or two of the weaker water, clear or diluted, may be applied to the part. Internally, ammonia may be used, first, to correct the gastric malaise that attends a fit of acid indigestion, or to allay nausea from any cause. For such purpose the aromatic spirit is specially devised, to be given in doses of from one-half to one teaspoonful, diluted with three or four volumes of water. Secondly, ammonia may be given for the constitutional effects of reviving the heart in faintness, of supporting it in chronic con- ditions threatening heart failure, of stimulating flagging respiration, as in dyspnea from lung disease, or in respiratory failure in poisoning by paralyzing agents, of allaying mild spasmodic seizures, and of opposing generally the action of narcotics and para- lyzers. For all internal medication the stronger water is entirely too strong, and the weaker water or. the spirit is to be preferred. Of the water or of the simple spirit from ten to thirty drops may be admin- istered at a dose, largely diluted. If swallowing be impossible, as in case of unconsciousness from a faint, the effects of ammonia may be obtained by inhalation, but great caution is necessary lest dangerous or even fatal irritation of the air passages be set up by too strong inhalation during complete or partial uncon- sciousness. None of the pharmacopoeial ammoniacal solutions should be applied close to the nostrils. 250 Ammonium Carbonate. — Upon subliming a mixtun of chalk and ammonium chloride or sulphate, doubli decomposition ensues, and a sublimate is obtained which consists of acid ammonium carbonate and ammonium carbamate, represented bv the svmhol NILHCO3, NH 4 NH,C0 2 . This composite salt is oil,. cial under the title Ammonii Carbonas, Ammonium Carbonate. It occurs as "white, hard, translucent striated masses, having a strongly ammoniacal odor without empyreuma, and a sharp, saline taste. On exposure to the air, the salt loses both ammi and carbon dioxide, becoming opaque, and is finally converted into friable, porous lumps, or a white powder. Slowly but completely soluble in about four parts of water at 25° C. (77° F.); decomposed by hoi water with the elimination of carbon dioxide and ammonia. By prolonged boiling with water the is completely volatilized. Alcohol dissolves the car- bamate [NH 4 NH 2 C0 2 ], and leaves the acid carbonate (ammonium bicarbonate). When heated, ammonium carbonate is completely volatilized, without charring The aqueous solution possesses an alkaline reaction and effervesces with acids." (U. S. P.) This salt must be kept in well-stoppered bottles in a cool place. Ammonium carbonate behaves, physiologically . like ammonia itself, but is a little less rapid and evanescent in operation. In concentrated solution it is locally irritant, and taken internally, dangero poisonous. The salt is used for the constitutional stimulant and sustaining effects of ammonia, and often for such purpose preferred to solutions ,,t ammonia because of the slightly longer duration of the action. It is given internally in frequently repeated doses of gr. iv. (0.25) in aqueous solution, with the acrimony disguised by gum arabic or sugar, or si agreeably flavored aromatic addition. Large s : doses should be avoided, since they easily overirritate the stomach and may excite vomiting. Ammonium carbonate is also much used to get an ammonia effect by inhalation. For this purpose it is coarsely bruised, treated with half its bulk of strong water of ammonia, and flavored with a little oil of lavender or bergamot, such mixture constituting what is knov smelling salts. Ammonium Acetate.— -This salt, CH 3 .COONH„ is used only in the aqueous solution in which it results from the procedure of neutralizing wit h ammonium car- bonate the diluted acetic acid of the Pharmacopoeia. Such solution, commonly called spirit of Minderi is official as Liquor Ammonii Acetatis, Solution of Ammonium Acetate. It is "a clear, colorless liq free from empyreuma, of a mildly saline, acidulous taste, and an acid reaction." (U. S. P.) The solution contains five per cent, of the salt. It should be made freshly for use, since like other solutions of alkaline salts of the common organic acids it tends to sponta- neous decomposition on keeping. Ammonium acetate is a bland, mawkish salt, which upon absorption may prove feebly diaphoretic or diuretic, according to circumstances, and may to a slight degree exert the characteristic effects of the ammonium compounds generally. It is used to allay headache, especially the headache of pyrexia, to quiet an uneasy stomach, or to promote gentle diaphoresis or diuresis in fevr; but it is at best a feeble medicine. One or two tablespoonfuls may be given at a dose, clear or diluted, sweetened and aromatized. The pharmacopceial dt is oss. (16. C). If diluted, carbonic acid water mal an excellent addition. Toxicology of Ammonia. — Ammonia is met with in commerce in a number of forms. First, as anhydrous ammonia condensed in large steel cylinders for use in ice machines. In these the ammonia is under a pressure of several hundred pounds and is in a liquid condition. When the pressun removed, the liquid assumes a gaseous form and issues from the opening as a colorless, irrespirable gas intensely corrosive to organic tissues. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ammonia and Ammonium Salts V number of fatal accidents have happened from action of this gas, either through the bursting of . cylinder when it has been highly heated, ur h imperfect connection with the refrigerating n'hine. Vxt, as the Aqua Ammonia Fortior and the Aqua of the pharmacist. Both of these are ied above. a solution of varying strength containing number of impurities, sold under the name of hold Vmmonia. Poisoning from gaseous ammonia is always the ,| accident, and such cases occur only in plants ie gas is stored or where it is used in quantity refrigerating purposes. Poisoning by inhalation the gas arising from its water solution has also own as the result of accident. When the gas is inhaled there is generally a sense of ion and giddiness, followed at times by vomit- i. The face is pale, and the pulse is faint and accel- In some instances the mucous membrane of e mouth becomes detached in the form of white ds, leaving the surface beneath intensely reddened v sure. The sense of taste is seriously im- ired for some time and the contact of solids with ch eroded surfaces is intensely painful. The effects of the inhalation of the gas are said to inflammation of the eyes and a diseased condition -kin. There is also a general lowering of the f the system with pronounced anemia. \\ hen applied to the surface of the skin, a strong lution of ammonia causes an intense smarting -at ion and the skin may become rough and ex- I through the corrosive action of the solution. When a solution of ammonia is swallowed, the tnptoms depend largely on the degree of concen- ution of the solution. When it is concentrated. there itly a strong smarting pain in the mouth and mat, which extends very soon to the stomach and ".vels. The abdomen becomes distended, and the ightest touch increases the pain. There is vomiting stringy matter having the odor of ammonia and metimes containing blood. The face is pale, the ion anxious, the inspiration hurried and linful. The pulse is feeble and rapid. The body covered with a cold perspiration. The interior the mouth is white or bright red, more or less >vered with shreds of mucous membrane, and the irte are greatly swollen. There is loss of voice and icre is also difficulty in swallowing. The thirst is tense and the mouth feels dry and parched. The >\v of saliva is greatly increased, in one case reaching ie amount of three liters in twenty-four hours. The rine is scanty, slightly acid or even alkaline in rear- on, and it may contain albumin and casts. The owels are sometimes constipated and sometimes the ■verse, the liquid dejecta at times containing much lood. If the patient dies from the immediate action f the poison, it is usually from suffocation on account f the swelling of the glottis. Some have died in a ondition of coma and some in convulsions. In a few :i". I dermal « ing; ma, me amnion; p.o.. region free from n derm; p. s., primitive streak. (Aftet Sehauinsland.) 252 REFERENCE IIAXDHOOK of THE MEDICAL SCIENCES ,ui. This band, known as the ectamnion, bends iliquely backward on each side of the head, extending ■i point aboul opposite the middle of tin- heart. the stage with twelve it thirteen somites, the head to the ectamnion, anil, bending downward, iks into the proamnion beneath it. At the same \d fold of the amnion, with tin' ectamnion rest, begins to grow backward over the head. 1 tir-t this is a fold of the proamnion, but by tin' ae it lias reached the midbrain, it is invaded by pc h ph pc I. — Transverse Section of the Albatross Embryo shown in ss, interior to the Liue ma. a, amnion; ao, aorta; ap t audi- v pit; />, brain; h, heart; m, mesoderm; nc, notochord; ,. -dium; ph. pharynx; 5, serosa; va, anterior vitelline vein. (After aauinsland.) Ida of somatic mesoderm from the amniocardiac . and the endodermal layer is withdrawn, bile the embryo is sinking gradually into the sub- rminal space and the amnion is growing over the ad, the ectamnion is extending backward along the - ;,- the crests of two lateral folds of the amnion igs. 91 and 92) which are continually being drawn in tween the embryo and the vitelline membrane and oieh fuse along the median line from in front ickward, beginning at the edge of the head fold of the anion. ac'. pc ph Fig. 00. — Seetion through the Line ma of Fig. 88. a. amnion; . amniotic cavity; c, ccelom; ea, ectamnion; ec, ectoderm: in, loderm; >■>, somatic, and sp, splanchnic mesoderm; other let- ring as in Fig. 89. When the anterior half of the embryo lias been ivered by the amnion, the outlines of the body are mpleted by tin' appearance of the tail fold of the pleure. Where the posterior limb of this fold ins the general surface of the blastoderm, the tail Id of the amnion arises. This grows forward over ic embrvo and, at the sides, becomes continuous ith the lateral folds. The amnion of the chick is thus formed by folds of ie somatopleure which meet and fuse over the median lineol the embryo (ae, Fig. 90). At the line of fu urn t lie ectoderm of each fold separates ami unites with its fellow of the opposite side. Tin' sami inn' of tin- mesoderm. In this way tin- exoccelom on each side of the embryo beCO S confluent, separating the two membrane I iei one i "■■ ei ing the embryo is the ami ion; the outer one lining thevitel- line membrane is the chorion, or membrana serosa ig. 90). This process of amnion formation in the chick continues to aboul the stage with thirty-one somites, when the embryo is completely covered ex- cepl for a very small opening called the arm Fig. 91. — Section of Fig. 88 behind the Head-fold of the Ainiu.m. a, amnion; ca, ectamnion; If, lateral fold; other letter- ing as in Fig. 89. umbilicus. This soon closes, but at this point the amnion and the chorion remain united, funning the \tic connection, which later becomes per- forated allowing communication between the amni- otic cavity and the albumen-sac. Among the other Sauropsida the development differs (1) in the relative time of beginning; (2) in regard to the importance of the proamnion; and (3) in the comparative size and form of the several folds. The amnion, in time of appearance, is earlier in reptiles and later in birds. It is earliest in the chameleon and latest in the hen. The chameleon is peculiar in that the amnion arises as a continuous elliptical fold surrounding the area embryonalis when the latter consists of but two germ layer-. h ac pc nc Fig. 92. — Longitudinal Section of an Embryo a little older than Fig. 87. a, proamnion; hf, head fold of amnion; mc, medul- lary canal; other lettering as in Figs. S8 to 91. After Schaninsland.) In general, according to Schauinsland (1902) the earlier the amnion appears, the greater the impor- tance and the longer the duration of the proamnion. In Sphenodon, a remarkable, primitive reptile of New Zealand, in which the amnion appears earlier than in any other reptile except the chameleon, the entire anterior part of the embryo is enclosed in the proamnion for a great part of the fetal life. The embryo is bent nearly' at right angles into the yolk and all of the amnion from the fore-limbs forward is free from mesoderm. 253 Amnion REFERENCE HANDBOOK OF THE MEDICAL SCIENCES In Sphenodon, the turtles, and some birds where the tail fold is wanting or poorly developed, the amniotic umbilicus is prolonged as a tube, the amni- otic duct, which extends backward over the blasto- derm and finally opens on the surface of the chorion. For the nourishment of the amnion, blood-vessels grow into it from the ventral wall of the embryo, about the eleventh day of the chick embryo. Some of the mesodermal cells of the amnion become differ- IV:. 93. — Section of the Blastocyst of a Hedgehog at the Stage when the Amniotic Cavity is a Cleft Between the Trophoblast and Formative Ectoderm, a, amniotic cavity; ec, ectoderm; en.endo- derin; tr t trophoblast. (After Hubrecht.) entiated into muscle fibers (beginning about the sixth day in the chick) and these, by their rhythmic contractions, are capable of rocking the infant bird at about the rate of sixteen oscillations per minute. Amnion Formation in Mammalia. — The Mam- malia are divided into three main groups: Mono- tremes, or Prototheria; Marsupials, or Metatheria; and placental mammals, or Eutheria. These groups differ in the character of their eggs and in their ontog- eny as much as they do in their adult structure. Fig, 94. — Section of the Blastocyst of a Hedgehog in which the Amnion is Complete, a, amniotic cavity; Co, ccelom; en, endo- derm; tr, trophoblast. (After Hubrecht..) In the Monotremes, which are oviparous with rel- atively large eggs (3.5-4 mm.) enclosed in a shell, the formation of the amnion probably is similar to what has been observed in the Sauropsida, but the steps in this process are at present unknown. Semon (ls'.M), however, has described the fully formed amnion of Echidna. An extensive proamnion is present, and a persistent seroamniotic connection extends the whole length of the fetus. The early stages in the development of the amnior of Marsupials is also unknown, but the fully formed fetal membranes of a number of species have beet described. Semon (1894) divides them into twi groups. In the one of which the opossum is a typi there is a remarkable development of the proamnion which envelopes all but the posterior extrerjQ of tin' embryo. Later, this is converted into amnion by the ingrowth of mesoderm from tin Fig. 95. — Human Embryo. Diagram of a Longitudinal Section a, Amnion; all, allantois; c, chorion; cs, connective stalk; c, area embryonalis; ec, ectoderm of chorion; m, mesoderm; //, yolk Bac. (After Spee, from Hertwig's Handbuch.) sides and behind between the two primary germ layers of the proamnion. In the other group the amnion shows no remarkable characteristics. The development of the amnion of the Eutheria i complicated by the entypy of the embryonic area, which in the new formed blastocyst is surrounded by an extra embryonic membrane, tin' trophobla I of Hubrecht. (See articles Area embryonalis and Blaaimlt nn.j Fig. 96. — Human Embryo "Gle." Dimension of blastocyat, exclusion of villi, S. 5X10X6. 5 mm.; length of area embi 1.54 i. Reconstructed sagittal section. All, allantois; Am, amnion; b.8, connective stalk; cho, chorion; Ec, ectoderm endoderm; mes, mesoderm; Vi, villi; Yk, yolk-sac. (Aftei from Minot.) According to Hubrecht (1912) the most primitive method of amnion-formation is that found in the hedgehog. This begins with a cleft that separates the trophoblast from the formative ectoderm of the area embryonalis. Later, this is roofed over by :> sheet of the extraembryonic ectoderm which, carry- ing a fold of mesoderm with it, grows up on all sides finally enclosing the cavity, which thus becomes the 254 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amnion amniotic cavity. The double layer of ectoderm and mesoderm which now forms its roof, is, of course, the amnion. The outer limb of the mesodermal [old unites with the trophoblastic ectoderm to form the diplotrophoblast, or chorion. (Figs. 93 and 94.) In a number of mammals is found a very simple type of amnion formation that Hubrecht regards as an example of accelerated development. In the ectodermal central cell-mass simply be- hollow. The floor of this cavity is the em- bryonal area, its roof is the amniotic ectoderm, which subsequently receives a mesodermal covering. ! in- amnion is found in this way in the guinea-pig, i in- hats, some insectivores, edentates, and probably in most primates. In the earliest, known human embryos, the Teacher- Bryce and the Peters embryos, the amnion and the yolk-sac are already formed. In both, the amnion is a simple globular cavity lined by a layer of ecto- dermal cells and surrounded by a solid mass of mesoderm. Spee's von Herff embryo (Fig. 95), which is somewhat ad- vanced in its other structures, has the amnion still in the ear- liest known condition. Then- is no evidence of any amniotic folds. The amnion is probably formed by the expansion of a split in the ectoderm of the inner cell-mass, as in the guinea-pig and frugivorous bats. In mice, the central cell mass is elongated, and he- comes tubular with the lumen closed at both ends; at the outer end by the trophoblast, at the inner end by the em- bryonic area. The amnion is formed by folds (a, Fig. 97) which constrict this cavity near the middle. In the majority of mammals the embryonic shield becomes spread out upon the surface of the blastocyst. This may fol- low a rupture of the tropho- blast over this area, as in Tar- sius, in some insectivores, and in the ungulates; or may be accompanied by a stretching of the trophoblast, as in the rabbit, where the tropho- blast over the embryonal area becomes very thin and finally disappears. In all of these mammals the amnion is formed by a folding of the somatopleure, very much as it is in the Sauropsida. The main differ- ence is that in the mammals the tail fold is generally more prominent, with the result that the point where the amnion finally closes is farther forward. In the cat, however, the head fold of the amnion is the first to appear, while in the dog amnion forma- tion begins with the tail fold (R. Bonnet, 1901). In both the dog and the cat, the mesoderm at first is continuous in front of the head region. But as the head develops, the mesoderm disappears from beneath it. In these animals, the proamnion is not a primary structure as in the chick, but is formed econdarily, and finally covers a considerable part of the embryo as it does in the rabbit (Fig. 99). Later, the mesoderm returns to the proamnion which thus becomes uniform in structure with the rest of the amnion. Tin Phylogeny of the Amnion. — The origin of the amnion and the history of its development in t lie course of phylogeny of the vertebrates is unknown. Paleontology furnishes no evidence, and we can only Speculate as to the probable history of the amnion Flo. 97. — Early Embryo of Mus Sylvaticus. En, lerm; c, cavity of umbilical vesicle; ol, tro- ist ; TV, proliferating trophoblast; Ec, embry- onal ectoderm; a, ecto- dermal cavity, the lower portion of which is after- rard cut off to form the amniotic cavity. (From Minot, after Selenka.) from such facts as may he gathered from embryology and comparative anal omy. First of all, I he writers on the history of the amnion may In' divided into t«o classes: i 1 ) those who regard the amnion as formed independently of the chorion, and (2) those who regard the amnion and the chorion as being due to the same process. (If the first group Hubrecht is almost the sole representative. lie regards the trophoblast which form- the outer layer of the chorion as a larval envelope similar to what is found in the echinoderms and -nine marine worms, where the body of i he first larval stage forms an envel- ope within which a small part of the body gives rise to the definitive embryo that developsinto the adult worm. Just as in certain groups of worm-, some species undergo such a metamorphosis, while in others the development is direct; so Hubrecht thinks that I he ancestral group that gave rise to the vertebrates early separated into two divisions. One of these lost its larval envelope and gave rise to Amphioxus, the cyclostomes and elasmobranchs, in which no trace of trophoblast has been found; the other divi- sion retained its larval envelope and its descendants include the ganoids, dipnoi, teleosts, Sauropsida, and Mammals, in all of which groups Hubrecht finds the trophoblast to be more or less developed. He regards the type of amnion as found in the hedgehog as the most primative and as having arisen in the holoblastic eggs (see Segmentation of the ovum) of the viviparous quadruped (Prototetrapoda) which first forsook aquatic life for the land and gave rise to the terrestial vertebrates. The oviparous habit, large yolk, and folded amnion of the Sauropsida, are, according to Hubrecht, secondary acquisitions. Although brilliantly expounded and supported by a wealth of facts, Hubrecht's argument is not con- vincing to the majority of zoologists, for several reasons. In t he first place, Hubrecht's hypothesis involves the theory of the amphibian origin of mammals, which is by no means universally accepted, although supported by certain morphological comparisons; as in the development of the heart, and ear bones, and the anatomy of the epiglottis and the intestinal arteries. In the second place, if we accept Hubrecht's views, we must believe that the Sauropsida have abandoned the viviparous habit for the oviparous one and that the yolk of these forms is not a gradual development from the conditions found in the present representa- tives of the amphibia, but has been acquired anew. This seems highly improbable, because it would seem to involve a loss of productive efficiency, and, moreover, the other groups of the animal kingdom present no analogy for such a course of evolution. Those who believe that the Sauropsida and Mam- malia have evolved independently from amphibian ancestors, must believe in the independent origin of the amnion in the two groups. This seems very improbable on general biological principles, and needs very strong support on morphological grounds, especially in view of the important results recently announced by Hill (1910). Without going into details, (for which see articles Ovum and Blastoderm) it may be said that Hill finds in the eggs of the Mono- tremes and Marsupials progressive stages connecting the Sauropsidian type of egg with that found in the higher mammals (Eutheria). Whatever views may be held regarding the morpho- logical history of the amnion, from the physiological point of view it must be regarded as an adaptation to a terrestrial mode of life. In the Ichthiopsida (fishes and amphibia), life is either wholly aquatic or else generally so in the larval stage, and either the whole egg is developed into the embryo, or else the embryo is folded off from the general blastoderm, which grows over the yolk forming a double layered yolk sac, that is eventually absorbed. In this case 255 Amnion REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the embryo projects from the upper surface of the volk-sac, as is well seen in the catfish. (Jlinot, 1903, Fig. 97.) The embryos of the Amniota, on the other hand, never project above the general surface of the blasto- derm, but sink into it, or else are developed from the first in a depressed area. In either case, the embryo is soon enclosed in the amnion, which is filled with a fluid. Thus, although on land, the young replilc, bird, or mammal really leads an aquatic life from conception until birth. Several authors have sought mechan- ical explanations of the origin of the amnion. Balfour tried to explain the amnion and chorion as formed by a folding of the somatopleure which results from the development of the allantois. It has been objected that, the amnion may be fully formed before there is any trace of the allantois. This disproves any direct mechanical effect; but, never- theless, the two organs may be geneti- cally related in tin' history of the race. We have many examples of the develop- ment of organs in ontogeny in anticipa- tion of their use. A woman develops breasts long before she has a child to suckle, yet we must believe the evolu- tion of mammas to have been genetically related to the production of offspring. Van Beneden and Julin sought for an explanation of the amnion in the effect of gravity, causing the embryo to sink into the fluid yolk. But Semon (1894) has shown that the embryo at first has less specific gravity than the yolk. Selenka regards the amnion as the direct mechan- ical effect of the development of the allantois and its distention with embryonic urine, combined with a bending of the embryo into the yolk that results from the cephalic and cervical flexures. Semon, on the other hand, has pointed out that the amnion is a protective organ that has been d<\ el- oped by natural selection in the course of evolution, and that it is not to be regarded as purely the result of the developmental processes of neighboring organs. In order that an animal may bring forth young on land, either the young must develop in the oviduct until viable in air, or the egg must be provided with a shell. The former is the primary condition according to Hubrecht, the latter, acording to Hill (1910), who makes the important suggestion that, "The acqui- sition of a shell by the Proamniota conditioned I In' appearance of the amnion. The loss of the shell in the Eutheria conditioned the occurrence in their ontogeny of entypy." Little reflection is needed to make il appear that Hill is probably correct. Deane has described the relation of the shell te the embryo in the chimeras, but it would be interesting in view of Hill's hypothesis to know what influence the shell has upon ontogeny in other fishes that have egg shells, as the skates, ami in what way the embryo is modified in the terrestrial amphibia that do not lay eggs in water but deposit in moist places eggs covered with a leathery shell. Anatomy and Histology of the Human Amnion. — The amnion in the fully developed afterbirth is a thin, smooth, translucent membrane lining the inner or fetal surface of the placenta and membranes. It rests upon the chorion, to which it is loosely at- tached — so loosely that it has some play on the chorion and can be easily stripped off. At the placental insertion of the umbilical cord the amnion merges into the integumentary covering of the cord, which, while corresponding to the amnion, differs from the latter in some important particulars. The amnion is made up of two layers: (1) a super- ficial ectodermal epithelial layer, and (2) a deeper mesodermal connective-tissue layer. 1. The inner free surface of the amnion, that di rected toward the fetus, is lined by a single layer o epithelial cells of ectodermal origin. These cells a an early period are thin, but later become thicker low columnar or cuboidal in form. At times, however in the mature state they appear thin and squamous The measurements of the dimensions of these cell; (diameters or diagonals) given by various obsen en vary from 0.008 to 0.012 mm. (Dohrn), 0.011 to 0.01! Fig. 9S. — Epithelial Cells Lining Inner Surface of the Amnion. Surface view. Silver nitrate and hematoxylin. X 1,000. mm. (Kolliker), 0.011 to 0.014 mm. (Lang.), 0.011 to 0.033 mm. (Nichols). The varying sizes of these cells, as stated by different observers, probably depend, partly at least, upon the degree to which the membrane is stretched in the process of prep- aration for microscopical examination. When hard- ened by the usual reagents without taking any pre- cautions, the membrane is apt to contract or shrink in superficial extent and at the same time to become * MM, Fig. 99. — Surface View of Eoithelium of Amnion from 1 It- Day Embryo, Showing Intercellular Bridges or 1' esses (pr) pi, Protoplasm (cytoplasm): nu, nuclei. XI, 225. (Miuot.) thicker, thus giving these cells an appearance of greater thickness and less superficial area: while when stretched on a cork and so hardened, the cells may be unduly stretched and thinned. Viewed from the surface, as after treatment by the silver-nitrate method to bring out the cell boundaries, these cells present the appearance of pavement epithelium, uniting in a single layer edge to edge, with often slightly wavy margins, and being in shape polygonal (often pentagonal and hexagonal), elon- 256 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amnion gated, or irregular (Fin- 98). Some observers have seen intercellular bridges uniting these cells (Fig. 99). Viewed in vertical sections, the amniotic epithe- lial colls appear as low columnar, cuboidal, or thinner ; the nuclei arc often situated near the free ends f the cells, leaving a clearer protoplasmic none in the per portions (Figs. 100, L03, 104). Che nuclei of these cells are rounded or spherical, about 0.004 mm. diameter. Most of the cells contain g single nucleus each, hut cells containing two, three, or four nuclei are common; these multinucleated cells of larger size than the uninucleated. In the latter part of pregnancy the epithelial cells sometimes un- dergo a certain degree of degeneration. Among these ■*;■-, v Mes - Msth Fir,. 100. — Section of Placental Portion of Amnion of Two- months' Embryo. Ec, epithelial layer; Afcs, mesenchymal con- ive-tissue layer; Msth, mesothelial or endothelial layer. 250. (Minot.) cells are occasionally observed round clear spaces or objects, which have been variously interpreted as stomata, vesicles, or cells that have undergone mucinous degeneration and burst. 2 Beneath the superficial epithelial layer is a con- nective-tissue stratum of mesodermal origin. This stratum can be divided into two layers: (a) a thick connective-tissue layer (mesenchymatous), and (b) in endothelioid (mesothelial) layer lining, par- tially at least, the outer surface of the amnion, that directed toward the chorion (n) The connective-tissue layer of the amnion, underlying the epithelial layer, makes up the larger part of the thickness of the membrane, and corresponds Fig. 101. — .Surface View of Nuclei of Cells of Amnion from Five- Months' Fetus. X 1,225. (Minot.) to that portion of the mesoderm which has been termed the mesenchyma. This layer is somewhat em- bryonic in character, and consists of connective- li-Mie cells embedded in an abundant matrix. The cells for the most part occupy the deepest plane of the amnion, often leaving in the upper portion of this connective-tissue layer, immediately beneath the epithelial layer, a zone that is free from cells (Fig. 103). The nuclei of these cells are at first rounded and oval, but later become irregular in form and size. The cells are flat and thin, arranged parallel with the surface. The shapes of these cells, especially in the ire amnion, have not been well made out; one specimen from a mature afterbirth in which the amnion had remained permanently separate from the chorion, presenting unusually favorable condi- tions for observal ion, (Fig. 102) has been examined by the writer (Nichols). In this instance the connect i ve- t issue cells were mostly huge flat cells, very irregular in form, giving off irregular processes and branches, some broad, some fine and filamentary. The proc- esses of neighboring cells were often directly con- tinuous with one another. The general outlines of the smaller of these cells were often roughly rounded; of the larger, polygonal or altogether irregular. These cells ranged in size from 0.025 to 0.100 nun. in extreme dimensions, measuring between the e.x- Fig. 102. — Connective-Tissue Colls from Mesenchymatous Layer of the Amnion. Silver nitrate and hematoxylin. X500. tremities of the processes (perhaps the specimen in which these measurements were made was somewhat, overstretched). Mingled with these larger cells were smaller rounded or oval cells, not so well provided with processes and ranging in size from about 0.008 to 0.016 mm. The intercellular matrix in which the connective- tissue cells of this layer are embedded is a homo- geneous ground substance said to be of gelatinous or mucinous character. At times, however, toward the close of pregnancy, the deeper portion of the layer (where the cells are mostly situated) becomes Fig. 103. — Section of Placental Amnion from Eight-Months* Embryo, ect, epithelial layer; mes, connective-tissue layer, show- ing non-cellular subepithelial stratum and deeper fibrous stratum. X340. (Minot.) markedly fibrous in character (Fig. 103), the outer subepithelial non-cellular stratum still retaining its homogeneous mucinous nature. The amnion of man is a non-vascular structure and contains no blood- vessels; the presence of an extensive system of lymph channels has not been definitely demonstrated, though such vessels may be present. The amnion of the chick is contractile, and is said to contain muscle cells. (b) The outermost surface of the amnion, that di- rected toward the chorion, is lined, partially at least, by a single layer of thin, flat endothelioid cells (Figs. Vol. I.— 17 257 Amnion REFERENCE HANDBOOK OF THE MEDICAL SCIENCES 100, 101). These are descendants and representatives of the mesotheliai cells which line the coelom and from which the endothelial cells of the pleura and peritoneum are also derived. These cells are nat- urally well marked in the early period of pregnancy, while the amnion is still unattached to the chorion and presents a free (.niter surface. A similar layer of cells probably lines the innermost surface of the chorion. After the amnion becomes united with the chorion, these cells would probably be suppressed at the points of union of the two membranes, though even at full term such cells have been seen at a plane corresponding to the deepest part of the amnion or innermost part of the chorion, perhaps lining spaces left between the membranes similar to lympn spaces in the bodv lined with endothelium. mes Fig. 104. — Section of Placental Amnion, at Term, cct , Epithelial layer; mes, mesenchyznatous connective-tissue layer; a, meso- theliai endothelioid layer. X 340. (Minot.) In the specimen of afterbirth above referred to, in which the amnion remained permanently separate from the chorion and presented a free outer surface, this layer of cells was nicely demonstrated by the silver-nitrate method (Fig. 105). On surface view these cells were mostly of hexagonal shape (some pentagonal and heptagonal), quite uniform and regular in shape and size, with slightly rounded angles. They were united to one another by their edges, which were straight, not sinuous. Their size was small, measuring 0.0055 to 0.007 mm. in diameter. They did not form a complete lining over the entire outer surface of the amnion, or at least they appeared only in patches; perhaps many of them were lost from degeneration. No nuclei were visible in them ■ — possibly another degenerative sign; if present, they did not take the nuclear stains employed. Patches of precisely similar cells were also obsen ed on the inner surface of the chorion in this case. The covering of the umbilical cord, which is continuous at the pla- cental end with the amnion and at the fetal end with the skin, differs in some marked characters from the amnion elsewhere. This covering consists of a superficial layer of epithe- lium, which rests directly upon the mucoflbrous tissue composing the chief part of the cord. The integu- ment of the cord is therefore intimately adherent to, or an integral part of, the cord, and cannot be stripped off as can the amnion elsewhere. The epi- thelial covering is composed at first of a single layer of cells, but later becomes stratified squamous in character, consisting of two to four layers of len- ticular cells. Union of Amnion and Chorion. — In its origin and early period the amnion is distinct from the chorion and separated from it by a space, which is the extra- embryonic part of the ccelom, and is homologous and at first continuous with the pleural and peritoneal cavities. After about the third month of pregnancy, in man, the amnion comes into contact with the Fig. 105. — Endothelioid Cells of Outer Surface of Amnion (and Inner Surface of Chorion). Silver nitrate. X 1,000. chorion, and the two membranes grow loosely together. The precise character of the histological connection between the amnion and chorion has not been well made out. Abxormalities of the Amnion. — Very rarely is the amnion the seat of abnormal or pathological conditions. Such abnormalities may arise in two ways: from anomalies of development, or from pathological processes. Among conceivable anomalies of developmeni the amnion might be: complete absence of the amnion; incomplete development of the amnion from failure of one of the amnion folds to grow; failure of tin edges of the amnion folds to unite, leaving a hi in the amnion and chorion; persistence of a coYd or connection of tissue between the amnion and chorion (the "amniotic cord"), such as normally occurs in ruminants: incomplete expansion of ami after closure, compressing the fetus. Some such anomalies of development have been occasion; observed in some animals, but in man they are exceedingly rare. A couple of human cases are recorded (Hamard) in which there was a separate small amniotic pouch around the abdominal insertion of the umbilical co The reporter of one of these cases attributed the con- dition to a rupture of the amnion (the chorion re- maining intact) with retraction of the amniotic mem- brane. Hamard, who reported tin- other case, con- sidered the condition to be due in both cases to an early anomaly in the development of the amnion. It happens, rarely, that the primitive separation of the amnion and chorion persists, in man, throughout pregnancy, so that the fetus to the time of birth is enveloped in two separate sacs, the amnion internally and the chorion (united to the decidua) externally. This constitutes a rare anomaly of the human after- birth, of which the writer has reported one case and cited seven other cases found recorded. Small nodules or caruncles have been observed in the human amnion, scattered about in considers numbers, some flat and sessile, some more or less pedunculated, and ranging in size from (hat of a pin- head to that of a pea. Structurally, these are of two kinds, one composed of epithelium, the other of con- nective tissue. The epithelial nodules are commoner and have little or no pathological significance; thy are small aggregations of epithelial cells. The con- nective-tissue nodules are composed of tissue like that of the mesodermal portion of the amnion; they are very rare, and have been observed in connection with early fetal death. Adhesions of the amnion to various parts of the fetus, with resulting deformities of the latter, I been observed. These adhesions have apparently been due to inflammatory action. Deficiency and excess in the quantity of the amniotic fluid, with the resulting pathological consequences, are considered in other articles. Amniotic Fluid. — The amniotic sac is filled with a serous fluid, the amniotic fluid or liquor amnii, in which the fetus is immersed. In quantity the amniotic fluid at full term in the hu- man female may vary greatly, but ordinarily ranges from about 500 to 1,000 c.c, averaging from 600 to 800 c.c. Abnormally there may be a deficiency (oligo- hydramnios) or an excess (polyhydramnios) of amniotic fluid, both conditions giving rise to certain pathological conditions and dangers. The differences in quantity at different periods of pregnancy are not well determined; it is quite possible that the fluid increases in amount during the earlier portion of pregnancy, and diminishes in the later portion. The liquor amnii is a serous or watery fluid, con- taining in solution a small proportion of protein, organic, and mineral substances. It is normally clear, limpid, and transparent, colorless, alkaline in reaction, and has a specific gravity of about 1.007 or 25S REFER KM IE HANDBOOK OK THE MEDICAL SCIENCES Amnion, Pathology 1.008. It contains from one to two per cent, of dry solids, besides a small amount of adventitious epithe- ligj cells, haii's, vernix caseosa, and occasionally leucocytes. Proteins (albumin, globulin, mucin, eto.) are present in the early part of pregnancy in large amount (10.77 per cent, at four months, 7.67 per cent, at fix e months, (i.ti7 per cent, at six mont h ! , l, hi undergo a great decrease toward the end of preg- cy, when there is only a small proportion present (0.82 per cent.). The inorganic sails present are those usually found in serous fluids, chiefly salts of i, potassium, ammonium, and calcium. Urea is present in slight proportion; t he aim unit is less early in pregnancy and gradually increases, 0.03 or 0.045 per cent, being present at the ninth and tenth months. (larked abnormalities in the physical and chemical racteristics of the amniotic fluid have been rarely encountered. \- io the source from which the amniotic fluid originates, there have been two opposing views: one that it is derived (in mammals at least) from the maternal tissues by transudation from the decidua through the chorion and amnion; the other that it is derived from the fetus, being the excretory products of the urinary or sweat glands of the latter. The view that the liquor amnii is of fetal origin has long been held; but in opposition thereto and in support of its maternal origin it has been urged by Minot that the fluid in its composition does not resemble urine, but is more of the nature of a serous fluid transuded from the blood-vessels: that the fluid appears before the urinary or other excretory glands of the embryo are developed and while the urethral outlet of the male is still imperforate; and that substances experi- mentally administered to the mother have afterward i found in the liquor amnii but not in the fetal tissues. On the contrary, the fluid occurs in saurop- sidan embryos which have lost their connection with the maternal tissues; and as to the finding of dines administered to the mother in the liquor amnii but not in the fetus, it is possible that the substances may have been entirely excreted and eliminated from the fetus and discharged into the amniotic fluid. Possibly in mammals the fluid is derived from both the fetus and the mother — from the mother at first and later from the urine of the fetus, but in man, according to Grosser, the latter source is not important. The function of the amniotic fluid is largely to ai end protection to the fetus in utero, by equalizing the pressure on all parts of the fetal body and pre- venting undue direct pressure of the uterine walls on particular parts of the fetus. By maintaining a symmetrical shape of the uterus, and protecting the umbilical cord and uterine walls from excessive and unequal local pressure, it obviates interference with the umbilical, placental, and uterine circulation. The amniotic fluid also permits the movement of the fetus in the uterus, and prevents adhesions of the fetus to the amnion or of parts of the fetus with one another from taking place. The symmetrical dis- tention of the womb by it facilitates and assists in the dilatation of the os uteri during labor. It has been also asserted that the amniotic fluid serves as a source of water for the fetus; as the fluid contains only a small proportion of solids, it could have little nutri- tive value except as supplying water. It is well settled that both mammalian and bird embryos swallow amniotic fluid; but whether this is done as a reflex act or for nutritive purposes, or whether the placental circulation is incapable of furnishing suffi- cient water to the fetus, is not known. J. B. Nichols. Revised by R. P. Bigelow. Referexces. Bonnet, R. (1901). Beitriige zur Embryologie des Hundes. 1. Fortsetzung. Anat. Hefte, 51 (Bd. 16, Heft 2), p. 232-413. Hill, J. P. (1910). The early development of the Marsupialia, with pecial ace bo the native cal I ' i iru rivin Q .1 Mir Sci., vol. hi., i>. I I ; i Hubrechti A. V. W. (18 ESarly ontogenetic phei lena in mammals and their bearing on ou pretal i ' I" phyli "i the vertebrates. Quart. Jour. Mic Sci . '■"! liii . pp. I 181. Hubrecht, V \. w 191 ! I ruhe I ntwicklungsstadien des [gels und ihre Bedeutung fur die Vorgeschichte Phylogi Amnions. Zool. Jahi b. Suppl 15 I estrchr ; , 19 771. Keibel, I . 1 1910 a), "i oung human ova .'en I embryos up to the formation ol the first primitive segment. Keibel and Mall's Manual of human embryology, vi i . p 2] !_' Keibel, F. (1910 6). The formation ol the germ layei md the i. >n pri >l ilera. f.c, p 13 Lillie, !•'. It. il'.ins). The developmei thechick. Nen York: Hell. Minot, C. S. (1903). Laboratory texl "logy. Phila Blakiston. Schauinsland, If. (1902). Die I atwickelung der Eihaute der Reptilien und der VogeL Hertwig's Handbuch, Bd. 1. Teil. 2, p. 177-234. Semen, Richard (1894). Die EmbryonalhtUlen der Monotre- rnen mid Marsupialier. Zool. Forsch. im Australien, Bd. 2, J.fg. 1. (l)enk. .Med nat. Gessel. Jena), p. 17—74. Si relit, II, (1902). Die EmbryonalhUllen der Siiuger und die Placenta. Hertwig's Handbuch. Bd. 1, Teil 2, p. 235-270. Amnion, Pathology. — The amnion is the inner- most of the membranes inclosing the fetus. It is continuous with the fetal epidermis at the umbilicus and forms a sheath about the umbilical cord. The exact manner of the development of the human am- nion is as yet unknown, for in the earliest embryos examined it forms a complete sac about the embryo. It probably arises through the vacuolization of a por- tion of the inner cell-mass, and is, therefore, a closed cavity from the beginning. Morphologically, it is a part of the body wall. It consists of two layers: an epithelial one continuous with the ectoderm, and a layer of embryonic connective tissue continuous with the somatic mesoderm. The epithelial layer is on the inside of the membrane, toward the fetus; the con- nective-tissue layer on the outside, next to the chorion and uterus wall. The membrane is thin and translucent, containing no blood-vessels, but is rich in large lymph spaces, forming lacunae in which the mesodermic cells lie. These spaces are connected by a system of very fine lymphatics. In the earliest stage the tissue of the .-minion consists of but two layers of cells (ectodermal and mesodermal), between which lies a distinct space. By the second month these layers have become united, and the mesodermal portion has increased greatly in thickness so that it is capable of being divided into two parts, a thin mesothelial layer covering the cho- rionic surface of the membrane, and the mesenchyma, which makes up the greater part of the fully devel- oped amnion. The tissues of the amnion do not normally develop beyond an early embryonic stage; the ectoderm preserves its one-layered structure, and the mesodermal tissue remains embryonic in char- acter. No blood-vessels or nerves have been found in the human amnion. In the later months of pregnancy, physiological degenerative changes occur in both mesodermal and ectodermal nuclei. The amniotic fluid (liquor amnii) is most probably, for the greater part, a secretion of the amnion, but the manner of this secretion or the source of supply to the amnion is still unknown. In the later months of pregnancy some portion of the fluid is undoubtedly derived from the fetus. It is probable that the fluid is secreted by the capillaries of the chorionic villi next to the amnion, and is passed on through the amnion by means of the activity of its cells. The fluid serves as a source of water supply to the fetus; and, as a mechanical protection against blows, shocks, pressure, etc., it assists in maintaining a uniform temperature, allows room for fetal movements, and aids in delivery. The amniotic fluid has a specific gravity of about 1.003, and contains about one per cent, of solids, chiefly 259 Amnion, Pathology REFERENCE HANDBOOK OF THE MEDICAL SCIENCES albumin, urea, and grape sugar. It occurs in greatest amount (J to % liter) at the beginning of the last month of "pregnancy, but diminishes to about half that amount at birth. During the first two months there is a definite space between the amnion and chorion, but in the third month the amnion is gradually pressed against the chorion, until an agglutination takes place be- tween the two membranes through the formation of a homogeneous fluid or gelatinous matrix containing few cells. This union is always very slight, as the amnion in all normal cases can be readily stripped from the chorion. In the first three weeks the mem- brane is somewhat removed from the embryo; in the fourth week the rapid growth of the latter almost entirely fills the amniotic cavity. During the second month the membrane enlarges more rapidly, forming a larger space for the amniotic fluid, but after the fourth month it fits more closely about the fetus, from which it is kept separated by the fluid. The structure of the amnion is analogous to that of the serous membranes, and there is consequently a close analogy between the general pathology of the fetal membrane and that of the latter. The tendency toward plastic exudations with the formation of more or less extensive adhesions, changes in the amount and character of the secretion, etc., occur here as upon other serous surfaces. The peculiar function of the amnion and its close relations to the embryo lead, however, to pathological processes peculiar to itself. Hematoma. — An effusion of blood between the chorion and the amnion may occur as the result of accidental or voluntary trauma, or of diseased con- ditions of the chorionic villi. Rupture of the umbili- cal vessels may lead to the formation of a very large blood clot between the two membranes. The small extravasations from the capillaries of the chorionic villi are relatively frequent and have little significance, but large ones may strip the amnion from the chorion over a large area, producing abnormal pressure upon the embryo and alterations in the amniotic secretion. Death of the embryo and abortion may result from these causes, or the pressure upon the amnion may produce adhesions between it and the fetus, leading to disturbances of development. The small clots are absorbed and replaced by new chorionic villi or fibrous connective tissue, or they may become calcified. Retrograde Changes. — The placenta and fetal membranes at term must be regarded as senile struc- tures, and certain retrograde changes must be recognized as a part of their physiological decay. These signs of age in the amnion begin as early as the fourth month, and manifest themselves chiefly by degenerative changes in the mesodermal nuclei, as shown by diffusion of chromatin, hydropic and fatty degeneration. Marked alterations in the shape of these cells occur in the later months, but these changes are probably dependent upon the tension of the membrane. Fatty Degeneration. — Minute fat droplets are very frequently found in the mesodermal cells of the mature amnion, and are to be regarded as physiological. In retention of the membranes after abortion this change may reach a pathological degree. Hydropic Degeneration. — This may occur to a limited extent in the mature amnion. In the rare cases of edema of the chorion the cells of the amnion become hydropic; and frequently, after death of the fetus, both the cells and intercellular substance of the mesenehyma undergo liquefaction. Myxomatous Degeneration. — A myxomatous degen- eration of tin' amnion may be associated with a similar change in the chorion. The mesodermal cells be- en branched, the intercellular substance more gelatinous in character, and small mucin-containing cysts may be formed in tin' mesenehyma. A hyper- plasia of the mesodermal cells may precede this change, and the amnion may be greatly thickened throughout, or villous-like projections into the am- niotic cavity may be formed. In very rare cases these may acquire such size that they may be classed as myxomata. These changes are of most frequent occurrence in the earlier months of pregnancy and usually follow the death of the fetus. Colloid-like Change. — The mesoderm of the am- nion not infrequently becomes homogenous and hyaline, loses its cells and slight fibrillation, and stains as colloid. The exact nature of this change is not known. It occurs rather frequently after the death of the fetus. Hyaline Change. — Portions of the amnion may undergo a proliferation of the connective-tissue cells, leading to the formation of a more mature connective tissue in which fibers are formed. The intercellular substance acquires a true hyaline character and stains rose red with Van Gieson's stain. This sclerosis in a limited degree may be considered as a senile change, but in the normal amnion it is never extensive, and the membrane for the greater part preserves its embryonic character. Any extensive hyaline change must be regarded as pathological. The causes and conditions of occurrence of this change are not known, but it may occur after the death of the fetus or in connection with syphilitic changes in the chorionic villi. Calcification. — Small plaques of calcification are not infrequently found at full term upon the inner side of the amnion, most frequently in the placental amnion. These most probably are calcified masses of fibrinous exudate or blood-clots. After the death of the fetus lime salts may be deposited in the amniotic meso- derm. This deposit may be preceded or accompanied by fatty, myxomatous, or hyaline change. The pathological significance of calcification, either of the chorion or of the amnion, is probably very slight, and the deposits of lime salts found in these structures at delivery, unless very extensive, are to be regarded as senile phenomena. H ypcrplasia.— After the death of the fetus the amnion may become much thickened from a hyperplasia of the mesodermal cells. The new tissue formed usually un- dergoes hyaline or myxomatous change or calcification. Localized hyperplasias may appear as new growths. The processes underlying these changes are practically unknown, but hyperplasia of the amnion is associated, at least in some cases, with syphilitic hyperplasia of the chorionic villi. Amniotitis. — Since the amnion contains no blood- vessels, a primary inflammation in the ordinary acceptance of the term cannot occur in the membrane. But the tissues of theamnion may become involved in changes which are so analogous in character and sequelae to inflammatory processes that the use of the term amniotitis may be accepted for practical reasons. Edema and liquefaction of the intercellular substance of the mesenehyma may occur; fibrinous exudates may take place, leading to the formation of extensive deposits of fibrin on the epithelial surface of the membrane, and to the presence of strings and bands of fibrin in the lymph spaces of the mesenehyma. The gelatinous tissue connecting the amnion and chorion may wholly or partially liquefy, its number of wandering cells may be increased, and in very rare cases pus may be formed between the two structures. In these cases there is also present a small-celled in- filtration of the chorionic villi. The umbilical cord may show a similar infiltration. Purulent placentitis is apparently very rare, and no well-studied ca es have been reported. I have seen two cases of pla- cental abscess resulting from infection of the placi through attempted abortion. In these the space b tween the chorion and amnion contained masses of fibrin and collections of leucocytes; the amnion "as swollen and colloid-like, containing fibrin strings and large numbers of leucocytes. In both of these cases the amnion was involved oy 260 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amnion, Pathology extension from the chorion ; and il is probable thai the fibrinous exudates, which are rather frequently found i,, ; , n , i upon the amnion, are the result of primarj pathological changes in the chorion or decidua. The existence of a primary amniotitis is yet to be proved. Ii has been stated that in cases in which the am- ,n itic fluid is absent or greatly reduced in quantity, the friction of the fetus upon the membrane Leads to the formation of plastic exudates and adhesions. It yel remains to be proved that such exudates are the direct result of changes in the amniotic cells. Iliai fibrinous exudates do occur has been con- firmed by numerous observers, but we are as yet at a to explain either their etiology or the manner of occurrence. Through the organization of fibrinous adhesions between the fetus and the amnion, • us bands may be formed which may lead to the production of marked abnormalities in the fetus. These adhesions may also be formed between the of the umbilical cord or between it and the body of the let us. Amniotitis is also regarded as one of the causes of hydramnion, the overproduction of the amniotic fluid being explained as of the nature ni acute serous inflammation. The proof of this remains to be established, but the fact that hy- dramnion and the formation of adhesions between fetus and amnion have followed traumatic injuries to mother may be taken as support of this theory. The amnion is not a perfect protection in so far as the entrance of bacteria is concerned. A number of ■ il amniotic infection have been reported. The pyogenic cocci, the tubercle bacillus, and other organ- isms are reported as having gained entrance through this membrane. The amnion must be regarded, therefore, as a possible portal of entrance for patho- genic microorganisms. In the later months of pregnancy the epithelium of the fetal surface of the amnion may be torn away in snips. According to Ahlfeld, this is the result of fetal movements, the epithelium being scratched by the finger and toe nails of the fetus. The amnion may burst in the last months of pregnancy, the ovum being preserved by the chorion. Through the movements of the fetus, the torn membrane may be mlled up into bands, which may become entangled with the umbilical cord and constrict it even to the extent of shutting off the fetal blood supply. Inflamma- tory changes have not been shown to follow these conditions. Amniotic Bands and Adhesions. — During the early stages of development of the membrane there may occur total or partial union of the amnion with the developing skin of the embryo. This union may be the result of an imperfect development of the mem- brane, in that it does not become differentiated from the ectoderm, or fits too closely about the embryo, BO that the amount of secretion is not sufficient to separate the amnion from the surface of the embryo. At the points of contact, union through direct fusion or intergrowth may take place; or a plastic exudate may be thrown out which unites the surfaces and later becomes organized after the manner of plastic exudates on any serous surface. It is still an unsettled Question as to how far these adhesions between the amnion and the fetus are to be referred to a pri- mary failure of separation and fusion, or to inflamma- t iry processes; but it is probable that in the majority of cases they are primary defects of development. Amniotic bands may also be produced by the rupture of the membrane, and the rolling up of the torn portions into bands or strings. In a case reported by Tetzer a rupture of the amnion had evidently occurred at an early month, with the rolling up of one portion into a fold, while from the other portion complete regeneration of the membrane occurred. rhese adhesions play a great part in the formation of monsters and malformations, and their teratologi- cs! inportance can hardly be overestimated. Bam Is and strings of union uol infrequently per i t at full term, and their connection with the mi shapen por- tion of the child leaves no doubt thai they bear a direct causal relation to the malformation. The structure of these hands ii uallj resembles that of the amnion, containing no blood-vessels; and they may be covered with epithelium. In other eases they in be regarded as prolongations and outgrowths of the fetal dermis, and con lain blood- vessels which arise from those in the fetal skin. Very frequently the only remnants of these bands al birth are short tags in the skin of the child. These have a tructure similar to thai of normal skin. Stretching of the adhesions through increase of the amniotic fluid may lead to their atrophy or to the formation of fibrous bands, which contain few cells and no blood-vessels and po i - no epithelial covering. A total adhesion of the membrane to the embryo causes marked disturbances of development of the head and extremities. Partial adhesions occur most frequently al the extremities of the embryo. An abnormal tightness of the cephalic cap may lead to marked malformations of the cranium, brain, Or face (acrania, anencephalia, exencephalia, cephalocele, cyclopia, arrhinencephalia, etc.) ; while abnormal tight- ness of the caudal cap produces a deficient develop- ment of the lower ext remities (amelia, phocomelia, etc). Clefts of the thoracic and abdominal walls, failures of closure of the dorsal and genital furrows, etc., are aNo associated with deficient growth of the amnion. Jt is impossible to say to what extent this association is one of cause and effect or merely a coincidence. If the amniotic fluid increases greatly in amount at an early period, portions of the adhesions may be separated and torn loose, floating in the fluid: or remaining attached at the ends, they may become stretched into fine threads and bands. These may entangle the extremities of the fetus and affect, their development through pressure and disturbance of blood-supply, or even cause intrauterine amputations. The variety of malformations produced in this way is very great. Larger bands of adhesions may divide the amniotic cavity into several chambers, and an over-accumulation of fluid in one or several of these cavities may result in the production of pressure malformations (club-foot, flat-foot, etc.). Hydramnion. — The pathology of an abnormal increase of the amniotic fluid remains unsettled. No constant pathological changes have been found in the membrane in hydramnion. It is evident that a number of factors may underlie this condition. It may be acute or chronic. The latter may be due to pathological changes in the mother (edema and dropsy from nephritis, cardiac disease, etc.), hyper- trophy of placenta and decidua, placental tumors, per- sistence of chorionic vessels which normally undergo obliteration, abnormalities of the umbilical vessels; or to pathological changes in the fetus (increased blood pressure, cardiac hypertrophy, obstruction of the ductus Botalli, syphilitic cirrhosis, fetal tumors, oversecretion of urine, as in the case of unioval twins, especially when one is an acardius and the other a maerocardius, ichthyosis and lymphangiomatous con- ditions of the fetal skin, etc.). Deficient absorption of the fluid may also lead to an overproduction of the fluid. In some instances, as in syphilis, disease of both the mother and child may contribute to an exces- sive formation of the fluid. Chronic amniotitis is a hypothetical cause. Acute cases following trauma to the mother have been ascribed to the occurrence of an acute serous amniotitis. Other cases of acute hy- dramnion arise without apparent cause. These cases are most common during the fourth and sixth months of pregnancy. OKgohydramnion. — A deficient formation of the amniotic fluid may occur, but the pathology of the condition is as obscure as that of hydramnion. It is commonly found in cases in which extensive adhesions 261 Amnion. Pathology REFERENCE HANDBOOK OF THE MEDICAL SCIENCES exist between the fetus and the amnion, and in the case of twins in which one sac may present a deficiency of the fluid, the other an excess. Imperfect develop] unit of the urinary apparatus (cystic kidney, imperforate urethra, etc) has been regarded as a probable cause. Abnormalities. — A large number of varieties of abnormal development of the amnion have been described. The most important of these, the bands and adhesions, have been mentioned above. Defects of the membrane, total or partial reduplication, for- mation of multiple cavities, etc., may occur. The etiology and the manner of production of these are unknown. A very rare anomaly is monoamniotic twin pregnancy. It is usually associated with acute hydramnion. Tuberculosis. — Primary tuberculosis of the amnion has not yit been reported. In one case of placenta] tuberculosis which I have seen, miliary tubercles found in the chorion just beneath the amnion, which was thickened and adherent, showing small- celled infiltration and signs of connective-tis ne proliferation. Tubercle bacilli have been demon- strated in the armniotic fluid and on the surface of the amnion. The rupture of chorionic tubercles through tin- amnion has been reported by Schmorl. Syphilis. — In syphilis of the fetus and fetal placenta a hyperplasia of the amnion similar to that of the chorion may take place. This may lead to a general or localized thickening of the membrane, and i- asso- ciated with various degenerative processes (fatty, colloid-like, hyaline). New Growths. — Cysts of the amnion have been described. These were small and without clinical significance. They were most probably due to a myxomatous degeneration of the mesenchyma. Der- moid cysts of the amnion have also been described. They may be single or multiple and may contain daughter cysts. They are most probablj- the result of errors of development and not to be regarded as true neoplasms. Small myxomatous projections into the amniotic cavity occur rarely. They are either localized hyperplasias or remains of adhesions which have undergone a myxomatous change. The exist- ence of true amniotic neoplasms is as yet doubtful. Extrauterine Pregnancy. — In extrauterine pregnan- cies, either before or after the death of the embi yo, the tissue of the amnion may undergo extensive hyper- plasia, ami become greatly thickened. It may con- tain new blood-vessels, which penetrate it from the external cyst wall. After the death of the fetus the entire amnion may become calcified, forming a cal- careous cyst wall, from which the mummified fetus may be easily shelled out (lithokelyphos) ; or if adhesions exisi between the fetus and the membrane, these may also become calcified, while the remaining portion of the fetus undergoes mummification (lithokelyphopedion). Aldred Scott YVarthix. Amoeba. — Ameba. A genus of simple protozoans of the class Rhizopoda, order Gymnamaebida, which have blunt or lobose pseudopodia and are without a shell or test. Tlii- genus i< non-pathogenic, but some nearly related forms like Entamoeba, Paramoeba, etc., are more or less important in connection witli cer- tain intestinal and other diseases. See Protozoa. A. S. P. Amok. — A Malay word meaning "an impulse to murder.*' .More commonly spelled annul.. Thi i pression "running amuck" is used to describe the action of a .Malay who suddenly and apparently with- out reason rushes into the street armed with a kris, bolo, or other cutting weapon and slashes or kills the f i i — t person he meets and as many more as possible until he is killed himself or put under restraint. The motive for this performance and the mental stati of the performer are QOl always clear to the white man in the East. The cases seem to fall into several categories. 1. In many cases it appears to be a genuine psycho- sis, a form of epileptoid seizure, or of manic-depres- insanity, the murderous outbreak being preceded and followed by marked emotional depression. 2. In other cases the action appears to be a form of religious frenzy carried out in pursuance of a vow. 3. In some instances it appears to be merely ar, of desperation resolved upon by the native in i sequence of domestic jealousy, gambling losses, or other misfortune or disgrace. In this form it is said to be an intentional mode of committing suicide, indirect mode taking the place among the Malays thai hara kiri has among the Japanese. Each case must be dealt with on its merits. W. \Y. Skeat says, "The act of running amuck is probably due to causes over which the culprit 3ome amount of control, as the custom has now died out in the British possessions in the Peninsula, the offenders probably objecting to being caught and tried in cold blood." J. F. Leys. Amphistomum. — A synonym for Gastrodiscua, a genus of flukes belonging to the order Malacoi family Amphistomidos. G. hominis has been four the colon and cecum of cholera victims. It i- an occasional parasite in man. See Trematoda. A. S. P. Amputation. — Amputation (Latin, nmputare. to cut away) is a term generally used to designate tin- removal by surgical operation of a portion or the whole of an extremity. In a wider application tin- word is still used with reference to separations of other prominent or projecting portions of the body, -u«h as the mamma, penis, and cervix uteri. In this article amputations of the extremities alone will be considered. Older writers, and many of the pn time in Germany and France, still further res tin- term amputation to the operative removal of a limb in its continuity, as in amputation through forearm or thigh, while they designate a- "disarticu- lations," "enucleations," the removal of a member in its contiguity {i. e. through the joint), tinction is properly ignored by English and Amei writer-, since many operations present combinations of the two procedures (Syme, Pirogoff). Historical Sketch. — The helplessness of sui of ancient times to cope with profuse hemo ally accepted as the sole admissible explanation of the fact that, for nearly two thousand years, from the time of Hippocrates to that of Pan'-, amputal were practically limited to the removal by cutting through the dead tissues of gangrenous extremities. The only reference to amputations in the Hippocratic writings is as follows: "In case of fractun bones, when strangulation and blackening of the parts lake place, at first the separation of the d living parts quickly occurs, and the parts speedily drop off, as the bones have already given way ; when the blackening (mortification) takes place . the bones are entire, the fleshy parts in this can quickly die, but the bones are slow in separating ai the boundary of the blackening and where the b< are laid bare. Those parts of the body which arc below the boundaries of the blackening ate to be removed at the joint as soon as they are fairly d and have lost their sensibility, care being taken not to wound any living part: for if the part which i- cut off give pain, and if it should prove to lie quite dead, there is gnat danger lest the pal swoon away from the pain, and such swoonings are often immediatelv fatal/' 1 The anatomical labors of the Alexandrian school could not have been without influence on the status of surgery. This we see illustrated in the surgical 262 REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Amputation writings of Celsus, who unquestionably was the first to suggest amputations in the living tissues above the line thai separates them from the sphacelus. While lie admits that patients frequently succumb during the operation from hemorrhage, there can be no ition I .ut that Celsus was acquainted with the ■ usefulness of the ligature. In Ids chapter on wound-, he advises that "if these [plugging the wound, compression, and mild caustics] do not pre- vail against the hemorrhage, the vessels which dis- charge the blood arc to he taken hold <>f and tied in places, aboul the wounded part, and cut through, they may both unite together and neverthele have their orifices closed." 1 1 seems scarcely possible that the theory, if not the practice, of surgery could have developed to the ion designated, unless a less difficult procedure for the ligation of a bleeding vessel in an open wound had been likewise perfected, particularly in view of the facts that Archigenes had introduced the tourni- quet, that every writer of the Greek and Arabian schools makes repeated reference to the use of the ligature for the relief of hemorrhage, and that torsion of bleeding vessels was advised under certain circum- jtances by Galen, Rhazes, and Paulus ^Egineta. It is quite certain, therefore, that the proper mam incnt of hemorrhage was not entirely lost sight of in the darkest period of the. history of medicine. Indeed, the indications for amputation seem to have a more elucidated fcr a time after the labors of is. Thus Archigenes enumerates, among the circumstances which require amputation, "the presence of intractable disease, such as gangrene, necrosis, putrefaction, cancer, certain callous tumor-, and sometimes wounds inflicted by 'weapon-." Nevertheless, the advanced position occupied by this writer was soon receded from. For a thousand years from the time of the latter authority retro- sion was the fate of amputations as of surgery in general. Where recourse to amputations was unavoidable, the most barbarous methods wi i i ted to. The Arabians operated with red-hot knives. Throughout the dark ages the actual cautery applied to the bleeding stump, or this was covered with boiling oil, or molten pitch, or sulphur. More cruel than any other was the practice of Guy de Chauliac, who in the fourteenth century bound a cord with sufficient force around a limb to insure its ival by gangrene. While amputations were dreaded, until within the last three centuries, alike by surgeons and patients, it is certain that this operation was not called for so frequently as it is now. Lacerations as terrible as those produced by machinery and firearms, which for the most part e the amputating knife into the surgeon's hands. could hardly have been often encountered prior to the discovery of gunpowder and steam. While Gersdorff of Strasburg probably had used the ligature in amputation wounds for some year-, it remained for the genius of Pare to give to amputations a comparatively firm position among surgical opera- tions. After nearly thirty years of experimentation and practical test of the ligature, he published results which should at onfee have revolutionized the surgical practice of the time. With the retraction of the skin and soft parts above the site of operation, to insure sufficient tissue to cover the divided bone, and the of a constricting band, Pare had adopted all the preliminary means which are deemed necessary to-day by many for making a circular amputation. Grasping the open mouths of the arteries with curved forceps, he closed them with a double thread, and the wound with three or four sutures. Likewise was Pare the first who clearly taught the value of the ligature en masse in refractory hemorrhages. "In- 1 by God with this good work," it would seem that Pare should have speedily moulded the prac of his contemporaries. That this was not the case is evident from the great opposition encountered by him, and that it required nearly two centuries for the ligature to supplant the actual cautery as a hemo- static measure. Although Fabricius Hildanu Germany, Dionys in France, and Richard Wiseman in England (last half of seventeenth century) make mention of the ligature, they in nowise recommend it. It is not remarkable, therefore, thai in the seven- teenth century, Botal did not hesitate to perf amputation by means of two hatchet-, one placed immediately below the member and the othi r loaded with leads let fall upon it ( \ elpeau), and that even as late as 1 70 1 W. Sharp saw cause for complaint at the restricted practice of ligaturing blei -el-. Indeed, it is questionable whether the ligature of Is in amputation wounds could even then have obtained a firm foothold without the assistance given to it by the tourniquet. The origin of the latter is enshrouded in mystery. There can be no doubt that II. \iiii < lersdorff made use of constricting bands. It appears that the idea of provisional compression of the artery, as now practised, was introduced inde- pendently by two surgeons of diffi i o mtries at about the same time. Morel, in France, and Young, in England, each devised a tourniquet for the arrest of the circulation. It remained, however, for the great J. L. Petit (1718) to elaborate the principles of arterial compression and to construct an instrument from which those now in use differ but little. Finally, with the introduction of digital compression and the use of the Esmarch bandage, the appliances for the control of hemorrhage appear as perfect as human ingenuity can make them. The most dangerous feature of an amputation being controlled, attention could be directed toward the securing of a more rapid cure and a useful stump. When, in ancient and medieval times, an amputation terminated well, a year elapsed before the wound had healed, and a conical stump usually resulted. In 1678 a friend of Thomas Young expressed his great surprise that larger extremities could be removed in such a manner that the wound was firmly cica- trized by first intention in three weeks. The circular incision for amputations being the one most quickly implished and intuitively resorted to by the earlier operators, was the one generally adopted. Although Celsus clearly indicates the necessity of completely covering the ends of the bone with the soft parts by dividing it upon a higher level, yet it was but rarely accomplished. This will not appear remarkable when we consider how the operation was described a- late a- the -ixteenth century by Hans von Gersdorff, the meat barber-surgeon of Strasburg: "And when you will cut him, order some one to draw the -kin hard up, and then bind the skin with your bleeding tape tight. Next tie a simple tape in front of the other tape in such a way that a space is left between the two tapes of one finger's breadth, so that you may cut with the razor between them. In this way the cut is quite reliable, goes easily, and makes a perfect stump. Now- when you have done the cut, take a saw and separate the bone, and after that undo again the bleeding tape and order your assistant to draw the skin over the bone and the flesh, and to hold it hard in front. You should have a bandage ready of two fingers' breadth; it should be moistened beforehand, so as to be wet through, then bind the thigh from above downward to the cut. that the flesh may protrude in front of the bone, and then bandage this too." Amputation by a single circular incision down to the bone has since been revived by Louis and Brunninghausen in the beginning of our century, and has been advised by Esmarch recently in emaciated and exhausted subjects. Early in the last century J. L. Petit originated the first decided improvement upon the ancient method of practising the circular incision. With the I circular incision he divided the skin and subcutane- 263 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ous cellular tissue alone, and after reflecting them divided the muscles upon a higher level by a second circular sweep of his concave knife. Cheselden and Sharp in England, and Heister in German}-, independ- ently devised and became adherents of this improved operation, by which the end of the bone could be completely covered. To still further improve the stump Edward Alanson, after the customary circu- lar incision through the skin, sought to give the wound a funnel shape by applying the knife obliquely and dividing the muscles in the form of a hollow cone. Subsequent operators finding, however, that the wound thus made was not conical, but spiral, and that it entailed conditions unfavorable to primary union, this modification failed to get a permanent foothold among recognized operations. A better and simpler means to produce a conical wound was pro- duced by Desault, who, after division of the skin, divided the superficial and deep muscles on different levels by two separate sweeps of the knife. Meanwhile flap operations had been devised. Al- though, according to Yelpeau anil Lacauchie, Helio- dorus had described amputation of superfluous fingers by the double flap operation, the knowledge of this method was entirely forgotten. R. Lowdham of Exeter in 1(579, introduced the flap operation for amputation of the leg by making a lateral flap on one side, a semicircular incision on the opposite side com- pleting the operation. The incision was made from without, and included the skin and muscles of the calf of the leg. Although, as already indicated, Young (currus triumphalis) most highly lauded the results achieved by the new method, it was ignored until Peter A. Verduyn of Amsterdam (1696), practised a similar amputation, transfixing the soft parts with a double-edged knife. Sabourin and Gar- engeot adopted the method by transfixion. Other modifications rapidly followed the first steps of the new method. H. Ravaton (1750) and Vermale (1767), surgeons of the Palatinate, recommended the for- mation of double flaps, while Charles Bell (1807) and the elder Langenbeck (Gottingen) again practically returned to the older operation of Lowdham. ( )n the other hand, Sedillot, in 1841, and Teale, in 1858, greatly improved the double-flap operation. Sedillot formed two musculocutaneous flaps, in which only a small part of the flesh was included, and divided the remaining soft parts by a circular incision. A number of operators advised that the flaps be of unequal size, lest the cicatrix become adherent to the divided end of the bone. Finally, Thomas Teale of Leeds (185S), devised the anteroposterior rectangular musculocutaneous flaps. Scoutetten of Metz in 1827, combined into what is termed the oval method a number of operations which had been previously employed by the elder Langenbeck, Larrey, Guthrie, and others. According to Scoutet- ten, this method, which is best adapted to disarticu- lations, is supposed to possess the advantages of both flap and circular operations. While, on the Conti- nent, this operation has found a small band of fol- lowers, it has never met with general favor. Indications. — Amputation has been termed the "last resource" and the "opprobrium" of the sur- geon. Recourse to this radical measure signifies the surgeon's unbelief in his efforts to restore to useful- ness an injured limb; it is his confession that, in the combat with disease, he has been conquered, or that his ability to rectify a congenital deformity is limited. To recognize the limits of his powers to save a part requires the keenest judgment of the surgeon, and it is remarkable how, in the history of amputations, this has swayed between the extremes of radicalism and conservatism. It is, of course, not remarkable that, prior to the introduction of the ligature, ampu- tations were, for the most part, confined to the re- moval of pails which were all but removed by an accident itself, or were already the seat of gangrene. On the other hand, the multiplication of methods of amputation, during the eighteenth and the early part of the nineteenth century, went hand-in-hand with the most reckless condemnation of limbs. The voices of Gervaise and Boucher, which were raised in defence of conservatism, were unheard, and even the remarkable reports of Bilguer were unable to stay the useless sacrifice of limbs. Bilguer, the fal of conservative surgery, and surgeon to Frederick the Great, could report, in 1763, 169 compound fractures successfully treated by conservative meth- ods. Among these were nine of the femur, forty- two of the leg, nineteen of the ankle, nine of the head of the humerus, sixteen of its shaft, twenty-two of the elbow, nine of the forearm, three of the wrist, and three of the hand. The distinction which these statistics brought to Bilguer was materially dimmed by the fact that he published his successes alone, and that for a while he denied amputations a place among justifiable operations. The incredulity of surgeons in these results and extreme views was one of the causes which prevented them for many decades from resl ricting the indications for an amputation. Faulty methods of treating wounds and an insufficient appreciation of the dangers attending major amputa- tions were likewise potent factors in so frequently forcing the amputating knife into the hand of the surgeon. The introduction of immovable dress- ings, the startling statistics of Malgaigne, published in 1842 and 1848, the favor with which excisions were received, and, above all, the advantage of anti- septic and later of aseptic wound treatment in the widest sense, were the chief causes in finally deter- mining the indications for amputations as they are now generally accepted. In general terms, it is proper to resort to amputa- tion when the sacrifice of a part, which is hope! diseased, is necessary to the preservation of life or the enjoyment of its various functions and duties. It is well to remember that " the vast majority of people would prefer living with three extremities to being buried with four." While in each individual case the danger and advantages of an operation are to be carefully balanced, conditions may arise which may make an operation imperative which but a few clay- before seemed uncalled for. Contraindications to amputation, either tempo- rary or permanent, should also be clearly recognized. Among the former, particularly as to amputations for injury, should be considered extreme shock and exhaustion from excessive hemorrhage. As perma- nent contraindications, such conditions should be recognized as will preclude the possibility of attain- ing the object of all operative procedure, viz., the restoration of the patient to health. Such indica- tions are, first, so extensive an involvement, by disease, of a limb and contiguous parts that ampu tation will not suffice for its complete removal and, second, complications on the part of important internal organs from injury or disease, under which circumstances an amputation would not on!. be useless, but would probably curtail life. While it is an axiom that amputation should be re- sorted to only under circumstance's in which no other means will avail, there is no little difficulty in deter- mining the conditions that call for this extreme measure. They may be most readily investigated by considering them under the three general headings of injuries, non-traumatic lesions, and deformities. Injuries. — (a) When, from accident of any kind, B limb is entirely severed from its connection, or the soft parts are so mutilated that it is attached by skin alone, or by it and pulpified flesh, an amputation is absolutely indicated. Wounds from circular sai railroad accidents, extensive gunshot lacerati afford numerous instances in which the amputal consists in nothing more than trimming off the ged edges of the wound, leveling the inequalities of 264 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation the protruding fleshy masses, and placing the stump in tin' best condition for speedy repair. To thi^ class of injuries belong those cases, caused by rail- iad trains, heavily loaded wagons, entanglement in machinery, etc., in which the soft parts are exten- sively torn from the bone, the muscles being pulpi- fied, the blood-vessels and nerves lacerated. It is remarkable that in instances of this character the skin itself may remain unbroken, while all that it ers has been practically crushed. The shock i ading the tearing off of a leg or an arm is usually : scessive thai a formal operation with attendant of blood must be dispensed with, i In the other hand, it is a well-established fact that fingers, portions of the nose and ear which had been almost completely and even totally separated by an incised wound uncomplicated by contusion, have been permanently replaced by the careful use of sutures. In amputating crushed parts of the hand ervatism is particularly desirable. Every part, e\ en of a finger, that can be sewed may be sen iceable. When a doubt exists as to the viability of a crushed part of a hand, an effort to save it should be made. In the event of death or uselessness of the part if saved a secondary amputation can be made. For this reason amputations for crushed wounds of the fingers and hand should in most cases be atypical. (b) Extensive hums and circumferential lacerations of only the skin and subcutaneous cellular layers may, in rare cases, require the sacrifice of a limb. When, from the depth of a burn, it becomes evident that the reparative process must be suppurative in character, and continue for many months, and when finally ended leave a disfigured and practically use- less member, it is usually better at once to amputate than to expose the life of the sufferer to the dangers of septic infection or exhaustion. Extensive strip- ping of the integument from a member may likewise impel the surgeon to operative interference. A most interesting case of this character is recorded by M. Schede, 3 in which an entire arm was caught in a cog- wheel and stripped of its integument, the muscles of the arm and forearm being laid bare as in a care- ful dissection. Although amputation at the shoulder was successfully resorted to and the acromion re- moved, the integument was insufficient for the closure of the wound. (c) The simultaneous injury of the main artery and vi in of an extremity has usually been considered an indi- cation for amputation, since it almost invariably results in its mortification if conservatism is practised. This has applied particularly to wounds of the femoral artery and vein. The advisability of an operation in all such cases must, however, be seriously questioned, since instances are multiplying in which with neo- plasms, several inches of the main vessels of the limb nave been removed without resulting in its death. When the vein alone is slightly injured, it is far pref- erable to trust to a properly applied lateral ligature, or if it is completely divided, an attempt to save the limb should be made by ligation of the accompanying artery. Quite recently a case has been recorded by Pilcher in which an incised wound of both femoral artery and vein was successfully treated by double liga- tion of both vessels. On the other hand, amputation may be required for the relief of traumatic aneurysms or those of spontaneous origin which have become diffused. Particularly may ablation of the thigh be preferable to other plans of treatment of aneurysm of the popliteal and of the deep arteries of the leg in persons of advanced years. In cases of subclavian aneurysm exartieulation at the shoulder has likewise been successfully performed as a modified distal liga- tion. Finally, secondary hemorrhage after injuries from whatever cause, when other measures have failed, can be relieved alone by the sacrifice of the limb. Since, after ligation in continuity of an artery, the secondary hemorrhage most frequently comes from the distal end of the vessel, it is apparent why amputation is often successfully practised. Rei advances in the surgery of the blood-vessels has made mi ervatism in these injuries practicable. Arterior- rhaphy and aneurysmonhaphy have in many ca done away with the necessity for primary amputation for injury Of eil her artery, vein, or both. () Inflammatory conditions of the bones and joints which cannot be relieved by less radical meas- ures may rarely make an amputation imperative. Acute osteomyelitis, when unrelieved by trephining, when affecting only a single bone, must be con- sidered a condition requiring this radical interference. Necrosis which involves the entire thickness of the shaft of the bone, as for example a part of the humerus, or the femur, and especially when repeated necrotomies have proved to be unavailing, occasionally requires the sacrifice of a limb. In extensive tuber- culosis of the articular ends of the long bones, or of the carpus and tarsus, when from the depraved condition of the patient excision is unfeasible, amputation is compulsory. The improved methods of dealing with suppurative and destructive affections of joints by immobilization, by the injection of formalin or, if need be, by resection, have happily reduced the number of cases calling for amputation from these causes to a minimum. (c) Extensive circumferential ulcerations of the leg, which sap the strength of the patient through hemorrhage or profuse suppuration, or which unfit him for the vocations of life, not unfrequently render amputation advisable. This also applies to cases of true and spurious elephantiasis, in which milder measures have proven of no avail. (d) Tumors of benign and malignant character, when from their size they destroy the usefulness of a limb or endanger life, are well-recognized indications for amputation. The neoplasms most frequently demanding the latter are carcinomatous degenerations of chronic ulcers or epitheliomata developing around a sequestrum, or an osteosarcoma of the articular ends of the long bones. Under all these conditions amputation offers a better chance for permanent recovery than does excision. For the central giant- celled sarcomata, curett ng or excision should be tried repeatedly before amputation is resorted to. The rule which applies to the management of neo- plasms generally, that an operation must lie refrained from unless all of the diseased tissue can be removed, is particularly to be remembered before an amputa- tion is determined upon for the relief of a tumor of an extremity. The bearing of amputation upon certain traumatic affections of the blood-vessels and upon special spontaneous aneurysms has already been referred to. Congenital telangiectases likewi e exacl amputation when rapidity of growth endangers life or when other plans of treatment have been unsuc- cessful. Deformities. — (a) Supernumerary fingers and toes are proper cases for removal, and the operation may be safely practised six months after birth. This early removal assures a better form of hand or foot and a diminutive scar. Cases of club-foot which have been altogether neglected or badly managed, and which, from extensive ulceration or infli id bursa-, entail great suffering upon the patient, not infrequently can be relieved by amputation only. But in early life no case of talipes is of sufficient severity to warrant the removal of the foot. (6) Cicatricial contractions of tin- joints, associated with great wasting of the muscles, from extensive burns; great deformity and uselessness of a limb from neglected dislocation (foot or ankle), may call for an amputation. For these and similar ca < . amputations of expediency may occasionally be required, but the surgeon should carefully weigh all factors in the case before subjecting his patient to the risks of an operation for the relief of a condition which in itself is only a burden and not a source of danger. To this category belong limbs useless In low the knee from infantile paralysis. Such legs are often burdensome from one cause or another (sensation of cold, proneness to superficial ulceration, etc.) and, since they are useless, it is probably better to amputate them and substitute an artificial Hint). The paralysis alone is not an indication for amputa- tion, since marvelous results may lie obtained from tendon grafting and its various modifications. Time fob Amputation. — When, in consequence of an injury, an amputation is indicated, the proper time for performing it must be considered. While the patient is still suffering from collapse, or even exhaustion from excessive hemorrhage, it would be sealing his fate to resort to an operation. At least moderate reaction may ordinarily be awaited, and hastened by the use of morphine, transfusion of salt solution with adrenalin, and possibly the strapping of the abdomen to raise the blood pressure. A moderate degree of shock is no contraindication to immediate amputation. Indeed, this may put an end to the shock by removing the afferent painful impulses from the dragging of the mangled limb, the added pain of the tourniquet, and the oozing. Wil h ether, or preferably gas-oxygen anesthesia com- bined witli cocainization of the larger nerve trunks, the amputation does not increase the shock but tends to end it. For from twelve to seventy-two hours, rarely more, an injured part may appear to remain unchanged, after which the evidences of infection or of tissue necrosis (gangrene) may become manifest. Primary. — All amputations practised prior to the advent of these changes are designated primary. Since the time when these changes supervene varies from one to three or four days, according to a multi- tude of circumstances, foremost of wTiich is the character of the wound and the extent to which it can be maintained aseptic, no absolute limit can be fixed to the time when an amputation should no longer be classed among the primary amputations. With very few exceptions, surgeons of the present day recognize the necessity for immediate amputation in every instance in which conservatism cannot be practised. The diversity of opinion which has pre- vailed on this subject has been great. Among the advocates of primary amputation may be enumer- ated Du Chesne, Wiseman, Pott, Percy, J. Bell, Larrey, and Guthrie; among its opponents, Faure, Hunter, and, in the last quarter of the last century, .1. NeudOrffer. Paul, and Cross. The extensive ex- periences of Guthrie and Larrey have finally con- vinced surgeons of the advantages of early, as com- pared with late, amputations. Of 291 primary 267 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES amputations, 107 recovered, twenty-four died, and 160 remained under observation. Of 551 secondary operations, 170 recovered, 265 died, while 116 re- mained under treatment (Guthrie). The accumu- lated experiences of the Crimean and Franco-Prussian wars, and the vast statistics of our Civil War, indorse the prevailing practice of resorting to early ampu- tations. In the statistics of Otis, there were in 3,259 primary amputations of the arm, 602 deaths, IS. 4 per cent, mortality; in 902 intermediary ampu- tations of the arm, 302 deaths, 33.4 per cent, mor- tality; in 411 secondary amputations of the arm, 114 deaths, 27.7 per cent", mortality; in 1,914 primary amputations of the lower third of the thigh, 927 deaths, 48.7 percent, mortality; in 676 intermediary amputations of the lower third of the thigh, 459 deaths, 67.9 per cent, mortality; in 207 secondary amputations of the lower third of the thigh, 100 deaths, 48.3 per cent, mortality. The obvious rea- sons for tin' better results which follow early opera- tions are that they are made at a time when the con- stitution has not yet been exhausted by protracted suppuration and high temperatures, and that they leave wounds which can be kept free from septic infection. Intermediary. — The second date at which an amputa- tion might be forced upon the surgeon is that during which the severest local and general signs of inflam- mation are present. The damaged limb has become red, edematous, and painful. From the wound there issues a sanious, malodorous fluid, and a more or less extensive sloughing of the tissues adjacent to the wound ensues. Associated with these local conditions are an acceleration of the pulse, elevation of the temperature, often to a dangerous degree, headache, dry tongue, scanty urine, and muttering delirium. Unless the patient succumbs to the paralyzing influ- ences of excessive temperatures, his condition be- comes gradually ameliorated in from five to fifteen days. As the discharge of scanty serum is followed by a free secretion of pus, the gangrenous parts are exfoliated, and the swelling largely subsides; the fever and acceleration of pulse are reduced; the tongue regains its normal moisture and color, and a comparative degree of comfort is enjoyed. Ampu- tations practised during this stormy period of the clinical history of an accident have, after the desig- nations of Boucher and Alcock, been called inter- mediary. Since they are made at a time when the damaged part and the system at large are in the very worst condition for operations, it is not remarkable that such amputations offer the worst prospects for recovery. Although the mortality following such amputations must, therefore, be very much greater than that following primary or late amputations, cases will arise in which the very gravity of the local and general phenomena, such as recurrent hemor- rhage, impending gangrene, or septicemia, will neces- sitate the speedy removal of the limb, as the last hope of deliverance. With improved methods of avoiding wound infection, in patients who are already septic, the terrors of so-called intermediary operations have been largely laid, although no statistics are available in proof. As an illustration may be cited the frequency with which success attends high ampu- tations for rapidly spreading diabetic gangrene and that in the presence of a high degree of acidosis. Secondary. — With the subsidence of the grave con- stitutional symptoms and the advent of profuse sup- puration begins that period when, if amputations are performed, they are termed secondary. It has already been seen that the prospects for recovery after amputa- tions in this period are less promising than after those of an earlier period. An equally strong objection to waiting for this period is that more of a limb must generally be sacrificed than by an early operation. Thus Guthrie observes that " When an amputation is delayed from any cause to the secondary period, a joint is most frequently lost: for instance, if a leg be shattered four inches below the knee, it can fre- quently be taken off on the field of battle and the joint saved. Three or four weeks after, the joint will in all probability be so much concerned in the disease that the operation must be performed in the thigh; the same in regard to the forearm and hand, and the upper part of the arm with the shoulder." Notwith- standing the drawbacks attending secondary ampu- tations, certain circumstances frequently make them imperative. Continued fever, impending exhaustion from excessive and protracted suppuration, and evident uselessness of the limb, even if saved, may force the knife into the hand of the surgeon, after much valuable time has been lost through an error of judgmenl on his part, or a procrastination on the part of friends. Anesthesia. — Many minor amputations of the fingers, of the toes, and parts of the hand and foot can very easily be performed under local anesthesia with cocaine, tropococaine, or novocain. In the same way by nerve blocking with cocaine, a badly lacerated limb can be removed by trimming the parts without resorting to an immediate formal amputa- tion. In almost all major amputations, however, a general anesthesia must be induced, and the choice is an important one. Chloroform should practically never be given, ether being preferable because it is a cardiac stimulant. In cases of severe shock, which so often attends the mutilations of the extremities caused by machinery, the anesthetic should be of gas-oxygen. Unfortunately it is a method that cannot be used outside of well A equipped hospitals and is a dan- gerous one, except in the hands of an expert anesthetist. Preparations. — Before begin- ning an amputation it is essential to make such preparations for it as are required for every major operation. If possible, the ampu- tation should be made in the early part of the day, in order that if there be much hemorrhage subse- quent to the operation its source may be looked for without artifi- cial illumination. It can be most satisfactorily performed on any operating table, or, in the absence of this, on two kitchen tables placed end to end. The instru- ments necessary for major ampu- tations are: 1. An Esmarch elastic bandage and strap for the produc- tion of anemia of the part to be removed. 2. A suitable tourni- quet. 3. Amputating knives of various lengths and widths, with at least one double-edged blade (catlin) (Fig. 106). 4. One large and one metacarpal amputating saw. 5. From six to twelve hemo- static forceps. 6. A bone-cutting forceps, and a lion-jawed forceps. 7. Ligature and sewing materials, drainage tubes, needles, and an abundance of hot water. Fig. 106. — Catlins. The preparations which are to be made for the after-treatment, although they are necessarily a preliminary to the operation itself, will vary according to the plan to be adopted, and will be considered at some length hereafter. While a finger or toe can be removed by a surgeon with only such aid as a layman can give, at least three assistants are required for every larger amputa- tion. The duties of these should be first clearly defined by the operator, lest valuable time be lost •jes REFERENCE HANDBOOK OF Till-: MEDICAL SCIENCES Amputation during the operation. The undivided attention of one must be given to inducing and maintaining anes- thesia. The second is to support the part to In- removed, after which he can be entrusted with the ligation of the vessels. The duly of the third should be confined to controlling the circulation of the limb above the seat of operation, and eventually to retract the flaps. These details arranged, the patient is anesthetized and brought into such a position that the limb to be removed is everywhere accessible. Tin- part to be removed must now be carefully wrapped in towels, the entire limb thoroughly cleansed with soap and brush, and the hair removed from the part wln-re the incision is to be made. The skin is then sterilized with tincture of iodine or a ten per cent, solution of iodine in benzine. The surgeon is then ready to take the final and most important prelimi- nary measure for the amputation, that by which he intends to control the circulation of the limb and reduce the loss of blood to a minimum. Prevention of Hemorrhage. — There are various methods by which the circulation may be more or less controlled during an amputation, and they are of sufficient importance to justify a detailed considera- tion. To prevent hemorrhage the surgeon can choose be- tween tourniquets, digital compression, and the Es- march elastic bandage, or combine the latter with one of the other two. T ourniquet.— From the time of Morel the ingenuity of sur- geons has been taxed to devise an instrument which will safely compress the main artery of a limb above the point where an amputation is to be practised. Of the many instruments introduced, only a few have been able to gain general recognition. The oldest of these is the Spanish windlass or garrote of Morele, which consists of nothing Fig.107.— Morel's Tourniquet. more than a wide band (Fig _ 107, g) of an unyielding ma- terial (muslin or linen), firmly drawn around the limb and tied. Over the main artery and at a point diametrically opposite, there are inserted under- neath it compresses of linen, a piece either of thick leather or of pasteboard (p). At a point opposite the artery a firm rod (s, s) is introduced underneath the encircling band and is then turned in such a manner as to shorten the latter, and thus the compression of the main artery is effected. Owing to the simplicity of its construction, the garrote of Morel stands without a peer in cases of emergency in civil as well as military practice. It has, however, one very objectionable feature which renders its use a matter of necessity rather than of choice. Not- withstanding the use of the pads of linen or leather already referred to, veins, arteries, and soft parts are compressed to an almost uniform degree; hence exten- sive venous hemorrhage and insufficient retraction of the muscles follow. A great improvement on the windlass is the tourniquet of Petit which was in gen- eral use until the Esmarch strap was introduced. It consists of two metal plates, the distance between which can be regulated by a screw, and which are con- nected by a strong linen band supplied with a buckle, by which the limb is encircled (Fig. 108). To apply it properly, the limb should be surrounded by a few- turns of a roller, while the body of the bandage (p) is placed over the artery (a). Over this bandage the lower metallic plate is then placed, and the band and buckle are fastened, when, by turning the screw 7 , compression of the main vessel can be regulated at pleasure. The objection has been raised to the tourniquet of Petit that it compresses not only the artery, but also its accompanying vein, and thus induces venous stasis, and enhances the dangers of thrombosis. While this is doubtless true, it is an insurmountable defect com- mon to all tourniquets, and based more on theoretical t nan on clinical data. \\ hen properly applied the tourni- quet of Petit is not apt to slip or yield, and its safety i< such that in case of emer- gency the management of the screw might be en- trusted even to a layman. In order to limit the com- pression to the main vessel alone, complete or incom- plete metallic rings have been devised which, while they surround the limb more or less completely, make compression at only two points, i.e. over the Fig. 108.— Petit 's Tourniquet, artery and at a point dia- metrically opposite. The best known tourniquets con- structed on this principle are the horseshoe tourniquet of Signorini and Dupuytren, the arterial compressor of the late Professor Gross, and the abdominal tourniquet of Pancoast and Lister (Fig. 109). While with these the compression can be limited to the main vessels of the limb, and the circumferential constriction of the latter is thus avoided, they are more liable to slip than the tourniquet of Petit, and are far less reliable than digital compression. For certain amputations, however (of the hip and shoulder), the instrument of Petit is inapplicable; it is then that one or other of the horse-shoe tourniquets or digital compression will be found indispensable. The tourniquets above described have for the most part only an historical value, they having been almost altogether supple- mented by the Esmarch apparatus. Digital compression, when made by trustworthy hands, is admirably suited to control temporarily the circulation. If compression of the artery alone is anatomically possible, it can be best accomplished by the finger. To be practicable, the vessel must be contiguous to a bone against which it can be pressed, as the femoral upon the os innominatum, the brachial upon the humerus, the subclavian against the first rib, or the abdominal aorta against the vertebra. Since only a few minutes are re- quired for the amputation of a limb and the ligation of the larger arteries, the endurance of the assistant entrusted with the duty is not severely taxed. In digital compression asso- ciated w-ith the use of the elastic bandage we have a combination by which the circulation of a limb can be completely controlled, and by which certain parts, the compression of which would be useless or even harmful, are protected. Notwith- standing the advantages of this method, the surgeon should never resort to it unless he can absolutely rely upon the ability and skill of Iris assistant. For ampu- tations' at the hip or shoulder direct compression of the common iliac through a laparotomy wound, or of the subclavian through an incision above the clavicle is justifiable. With unreliable assistance temporary ligation of these vessels would be an absolute safe- 269 Fig. 109. -Horseshoe Tourni- quet. Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 110. — Esmarch's Apparatus. (Bandage not shown in cut.) guard against excessive bleeding. Digital compres- n >n is especially indicated in amputations for senile gangrene when the diseased condition of the main artery is likely to be made worse by the prolonged pressure of a tourniquet. Elastic Compression. — Notwithstanding the pre- cautions against hemorrhage after amputations, these were invariably associated with very great loss of blood until twenty years ago. The blood thus lost was venous in character and came from the veins of the amputated member. Through the practices of Grandesso Silvestri, an Italian surgeon, and particularly of 1 }smarch of Kiel, the blood contained in the part to be re- moved is saved, and that this is not an in- considerable quantity has been demon- strated by experi- ment. The apparatus of Esmarch consists of an elastic bandage and an elastic tube or flat band with chain or clasp attachment. Commencing at the fingers or toes, the bandage is applied by spiral turns until the limb is covered to a line at least four inches above the point u here the bone is to be divided. Above the last turn of the bandage, the elastic band or tube is rather firmly and repeatedly wound around the limb, and secured by clasp or hook and chain (Fig. 110). When the bandage is then removed, a condition of ischemia is observed in the limb, which will permit its ampu- tation without a more than appreciable loss of blood during the operation proper. In recent years the elastic bandage is used less and less, because of the danger of disseminating the infective or malig- nant process for which the amputation is to be done. By elevating the limb for five minutes be- fore applying the strap, complete ischemia can always be induced. When the elastic strap is re- moved, the integument of the stump rapidly assumes a bright-red color, and in the wound there appears free, persistent, and often embarrassing, capillary oozing. It is generally accepted now that the source of this hemorrhage is from the dilated capillaries, the walls of which have been paralyzed in conse- quence of the pressure exerted by the strap on the vasomotor nerves. When in from twenty to thirty minutes the vessel walls regain their tonicity, the hemorrhage ceases. To check this capillary oozing, a number of remedies have been suggested. That of Riedinger, to apply the faradic current, while very serviceable, is not always practicable. Es- march relies upon closure of the wound and elevation of the stump before the strap is entirely removed. Hot water (150° to 180° F.), applied with sponges, often acts admirably in these cases. Since compres- sion of the vasomotor nerves caused by the bandage is the cause of this parenchymatous hemorrhage, this can best be obviated by completely substitut- ing digital compression for the elastic strap, or, if the latter be used, by preventing the ingress of blood by the use of a tourniquet until the vessels have re- gained their natural tone. The latter plan, as practised bj Ashhurst, is "to place a tourniquet in position, but not screwed down over the main artery of the limb, and then to apply the Esmarch tube a few inches above the point at which it is intended to am- putate. As soon as the principal vessels have been secured, the tourniquet plate is screwed down and the tube removed. No bleeding follows, and by the time that the remaining arteries requiring ligatures have been tied, the vessels will have regained their tone, and the tourniquet can be removed without any risk of bleeding following." In amputations near the trunk the elastic strap or tube should not be used in the ordinary manner (see Special Amputa- tions). In an amputation of the shoulder, and in another of the hip, I have seen it loosen or slip over the stump immediately after the disarticulation effected, and in both instances (lie hemorrhage was most alarming. In amputation at the shoulder, when, by the use of the bandage, the blood in the extremity has been returned to the economv, it is better to rely upon compression of the main artery against the first rib with the finger or a padded key. In amputations of the hip, the main artery cat compressed against the pubic bone, or even the cir- culation in the aorta can be controlled by one of the many compressors already referred to. In consider- ing amputations of the shoulder, of the hip, or of I he ilium special methods of controlling hemorrha applicable to them will be discussed. Methods of Amputation. — Every amputation consists of three steps: (1) Division of the soft pa (2) division of the bone, or disarticulation; (3) 1 tion of t lie vessels and closure of the wound. According to the method adopted for the division of the soft parts, amputations are classified as cir- cular or flap operations, and in the choice of tin- method the surgeon must be guided by the condition of the soft parts about the bone, the ease with which the joint can be opened in a disarticulation, the prob- able position of the cicatrix and form of the slump, and, above all, the desire to save as much of the limb as possible. Of the circular and flap operations, all methods of amputation may be said to be but modifi- cations. By the circular method it is attempted to give to the stump the form of an inverted cone or funnel, the apex of which is occupied by the divided end of the bone, the base or margin of which is rep- resented by the cutaneous margin of the wound. In the flap operation the soft parts are so divided as to make one or more flaps, the bases of which are on a level with the divided bone, and the free margins of FlQ. Ill which are so adapted to each other as completely to cover the bone and admit of the ready closure of the wound. Whatever plan of operation is adopted, the surgeon should stand in such a position that he grasps the stump with his left hand, so that the amputated part falls toward his right side. Circular Method. — All modifications of the circu- lar method call for a similar incision through the skin and subcutaneous cellular layer, this incision being made around the entire circumference of the limb ami at a right angle to its axis. According to the depth to which the incision is carried, the method is sub- 270 REFERENCE HANDBOOK OF THE MEDICAL SI 1ENCES Amputation divided into that by single incision and that by double incision. . Single Incision.— This, as already remarked (see History), is the oldest method of amputation, and is generally known as the Celsian operation. Alter tction of the soft pari-, a long amputating knife is -wept around the limb, and all of the soft parts are divided down to the In. no. This is then divided on a slightly higher level by the retraction of the soft parts. Wnile'this operation yields the smallest wound, and i< the most rapid in it's execution, its manifest disad- vantage is in the insufficient covering which it affords for the bone. It is admissible only in greatly emaciated subjects. Brunning- hausen, in the begin- ning of the century, reintroduced this method, but, after Fia. 112. the amputation of the limb was completed, made a second section of the bone several inches above the point at which it was first divided. Double Incision. — This operation of which those of Petit, Cheselden, B. Bell, Desault, and Alanson are but unimportant modifications, has received its name from the fact that the skin, underlying fascia, and muscles are divided upon different levels, and there- fore by at least two circular incisions. It i< made as follows: The surgeon, securely holding the limb with the left hand, carries his right hand, in which he firmly holds a large amputating knife, underneath and around the limb until the heel of the cutting Fig. 113. edge is over the uppermost part of the line of the proposed incision. Giving the knife this position forces the operator into a more or less stooping pos- ture, from which he raises himself as the incision is completed. This is commenced with the heel of the knife, winch, by a single sweep is carried around the entire circumference of the limb, severing the skin and adipose layer down to the deep fascia (Fig. 111). Two incisions, the ends of which meet, will answer as well as the division by a single sweep of the knife. As soon as the integument is divided the wound gapes. The upper margin is raised by the thumb and finger of the left hand, and gradually detached from the fascia by repeated long incisions carried perpen- dicularly to the axis of the limb. This operation of detachment is continued until the skin and adipose Fig. 11 1. layer can be reflected like a cuff, the length of which should be equal to half the diameter of the limb (Fig. 112). When the latter rapidly increa e in circum- ference, or there is a thick subcutaneous layer, oi this has been infiltrated, the reflection of a cuff is often impract icable. 'I ben two longitudinal inci- sions, diametrically op- posite each other will materially facilitate this part of the opera- tion, although by this means the amputation is in a manner con- verted into a Hap oper- al ion. The integument having been reflected to the required extent, the muscles are next divided close to the line of reflection by one steady circular sweep of the knife, which should cut through everything down to the bone (Fig. 113) or rather to the periosteum. Before using the saw, the bone should be stripped of its muscle and a periosteal cuff made, which after the division of the bone falls natur- ally over its raw surface, and applies itself to the open medullary canal. Where there is no oozing it may even be sewed in place advantageously with catgut sutures. In dividing the muscles it is often desirable to do so on different levels whereby the wound naturally assumes a cone-shape and is more easily closed. Where there is but one bone to be divided, the surgeon is now prepared to use the saw. Where there are two bones, the interos- seous tissues re- main to be divided. Whereas this can be accomplished with an ordinary amputating knife, it is safer to use a double-edged in- strument (catlin) for this purpose. By using it in the fig. us. manner indicated in Fig. 114, there is no danger of cutting the blood- vessels twice, and thus one danger of troublesome hemorrhage is avoided. To protect the soft parts from injury by the saw they must be well retracted by the hands of an assistant, or by the use of a band of muslin (retractor) divided into two or three slips according to the absence or presence of an interosse- ous space (Fig. 115). The movements of the saw can be greatly facilitated by guiding them with the nail of the left thumb (Fig. 116). The to-and-fro movements of the saw Fig. 116. should be slow, lest the heat developed by its too rapid use endanger the vitality of the bone. Where there are two bones of the same diameter (forearm), they should be divided simultaneously. In the leg, 271 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 117. the tibia is to be almost entirely divided before the section of the fibula is commenced. Unless this precaution is adopted, splintering of the bone is not easily avoided. For the same reason, the assistant in charge of the part to be amputated should hold it horizontally, allowing it xaW neither to , J-Jft drag by its L*J MWmi weight nor to be raised in a manner to in- terfere with the move- ments of the saw. Should splintering of t h e bone neve rtheless occur, the splinters and sharp margin of the latter must be re- moved with the cutting bone forceps. Oval Method. — Holding an i n t ermediate position be- tween the cir- cular and flap operations is the oval method, which, although practised by the older Langenbeck and others, was first generalized by Scoutetten (1827). The essential feature of this amputation in the continuity of the limb is that the incision, instead of being made perpendicnlar to its long axis, is carried at an angle of forty-five degrees, and in such a way that the soft parts in front of the bone are divided upon a higher level than those on its posterior aspect. At the same time the upper portion of the wound is converted into an acute angle, whereas its lower portion is given an oval outline. The upper extremity of the wound is placed at the point where the bone is to be divided. The operation is com- menced by two incisions in the form of an inverted V, the lower ends of which are united by a transverse cut on the posterior sur- face of the limb(Blasius). Here, as in the circular am- putation, by a single inci- sion all the soft parts are divided at once on each side of the bone, and then those on its posterior aspect. This operation has been generally discarded for amputations in the continuity, although for disarticu- lations at certain joints it presents advantages which an 1 worthy of consideration (see Fig. 117). Flap Method. — As already indicated, this consists in the formation of one or more flaps, comprising integument and muscular tissue, or integument alone, and designed in a manner completely to cover the divided extremity of the bone or its exposed articular surface. According to the anatomical components of the flaps, they can therefore be called tegumentary and musculotegumentary. Tegumentary Flaps. — This operation is generally practised by making two semilunar incisions, the ends of which meet on opposite sides of the part, down to the deep fascia, and dissecting up the skin and subcutaneous cellular layer to an extent sufficient Fig. 119. to cover the stump (Fig. 118). When it is practicable, the flap should be taken from the anterior and pos- terior aspects of the limb in the forearm, thigh, and leg, and they should not be of equal lengths, the anterior flap usually being made longer, to fall like a curtain over the divided end of the bone, where it comes in contact with the posterior (shorter) flap. In recent years the tegumentary method, with only one cutaneous flap, made from the anterior surface of the limb, has been most highly advocated (Garden, Bruns). When, from choice or necessity, a single tegumentary flap is to be made, the incision should be commenced on a level with the point where the division of the bone is contemplated, and carried for a varying distance down one aspect of the limb, parallel to its axis, and then by a wide curve on the opposite side to a point on a level with its commence- ment (see Fig. 118). In this manner the base of the Fig. 120. cutaneous flap extends over half the circumference of the limb, while its length should be greater than its anteroposterior diameter at the level of the amputation. After separation of this flap from the deep fascia (it may be made to include this) it is reflected and the ends of the incision are united by a posterior incision carried perpendicularly to the axis of the limb as in the circular operation (Fig. 119). Whether one or more cutaneous flaps be made, the division of the remaining soft parts is practised by a single sweep of the knife, carried perpendicularly around the limb at the base of the flap, as in the circular operation. Owing to this division of the 272 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation muscles, amputations by the tegumentary flap method are not infrequently called "modified circular operal ions." Musculotegumentary Flaps. — Here, as in the tegu- mentary method, one or more Haps may be made to rever the stump. They may be formed by transfixion of the limb and cutting from within outward, or by cutting from without inward, or by making one flap by the former and the other by the latter mentioned method. Where there is but a single bone (thigh, arm), it was the custom of the older surgeons to make at least one flap by transfixion. The integument being well retracted, and the soft parts raised from the bone with the left hand, a sharp-pointed and large amputating knife is passed through the limb from side to side, the knife being made to graze the surface of the bone (Fig. 120). By a sawing move- ment the instrument is gradually carried downward and forward, and then obliquely outward, thus form- ing a wide flap with convex margin. The danger of making a flap too narrow is best avoided by not cutting outward too soon. The knife is then entered at the angle of the wound on one side, passed around the bone on the side where the soft parts are still adherent, and out at the opposite end of the wound. The second flap is then made by cutting outward as before. The flaps being now retracted, the knife is rapidly carried around the bone, as high as possible, to divide the muscular tissue still adhering to it. The application of the saw then follows. In order to make sufficient allowance for shrinkage, the flaps should have a length at least equal to three-fourths the diameter of the limb. Redundance of the flap is always preferable to insufficiency, since the excess of muscular tissue can easily be removed with a few strokes of the knife. In flap operations, owing to unequal retraction of the soft parts, tendons and nerves are particularly apt to protrude above the surface of the wound, thus giving it an irregular appearance, and interfering with its ready union. After ligation of the blood-vessels, these protruding masses are to be carefully removed with the scissors. The protrusion of the muscular tissue of the flap and the irregularity of the latter can be totally avoided by cut- ting from without inward. This plan, generally known as that of Langenbeck (Fig. 121), insures perfect symmetry of the flaps, Fig. 121. and permits the ligation of the vessels as they are exposed or divided. It is also practicable to cut through the skin and subcutaneous tissue from with- out inward, and complete the operation by transfixion. Although already practised by Dupuytren, this plan was advocated later by Agnew.* Most surgeons who prefer accuracy to speed will fashion their flaps by cm ting them from without. Rectangular Flap. — In 1S55 Mr. Teale of Leeds practised the formation of one long and one short rectangular flap, each of which comprised one-half the circumference of the limb and all the tissues down to the bone. The operation is made as follows: A rectangular anterior flap (posterior in the forearm), equal in length and breadth to half the circumference of the limb at the base of the flap, is marked out by one transverse and two parallel longitudinal incisions, the latter involving only the skin and superficial fascia, and the former being carried down to the bone. Vol. I.— IS Fig. 122. The longitudinal incisions should be so placed that the posterior obtains one-fourth the length of the anterior Hap. The two flaps are then turned up from the bone from below upward, and the saw is applied. To insure equal width of the Haps at their bases and their extremities it is besl to map out the Haps by actual measurement before tin- incisions are made. In closing the wound, the long Hap is doubled upon itself so that the square ends of the two flaps are brought into apposition, where they are retained by a number of sutures (Fig. 122). Comparison of Methods. — The surgeon who would obtain the 1 best results after amputul ions should be familiar with all the different methods without becoming too partial to any, since the condition of the part to be ampu- tated, the thick- ness and vitality of the subcutane- ous cellular tissue, the position of the wound, and many other circum- stances should guide him in the selection of a m e t h od ra t her than individual preference. To save as much of a limb as possible must be the first aim of the opera- tor, and this can be accomplished only by resorting to various methods according to the exigencies of individual cases. If one method of operating deserves a preference, it is that by tegumentary flaps with circular division of the remaining soft parts. By this method the posi- tion of the angles of the wound for favorable drainage and that of the cicatrix can be readily determined, and when two oval cutaneous flaps are made no anxiety for their vitality need ordinarily be enter- tained. When the subcutaneous cellular layer is very thin, there is a manifest advantage in dissecting up with the integument some of the superficial muscular fibers. The marked advantage of the tegumentary flap over the circular method lies in the fact that by it, when the disease extends higher on one side of the limb than on the other, it often enables us to ampu- tate several inches lower than we could by the circular method. While during the early part of this century the musculocutaneous method by transfixion was very extensively practised, on account of the rapidity with which it could be executed and the muscularity of the stump which it left, it is gradually being dis- carded for two reasons chiefly. In the first place, the general use of anesthetics has removed the necessity for unusual haste, and in the second place, the muscu- lar tissue left in the stump generally undergoes atrophic changes from disuse during the first year. A most decided disadvantage of the musculotegumen- tary flaps exists in the oblique division of the blood- vessels, on account of which they are often difficult to find and to ligate. It is for this reason that sec- ondary hemorrhages are more prone to follow ampu- tations made by this method, although by proper care in the act of ligation and with sufficient compression of the stump with the dressing this can usually be avoided. The circular operation commends itself, owing to the facility with which it can be executed, even by a novice in the operative art, and by its special applicability for amputations in certain parts, as in the forearm and lower part of the leg. Where the operator can choose his method, amputations may be made with good results as follows: In the 273 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES arm and forearm, by circular method or rectangular flaps; in the upper part of the leg, by tegumentary and rectangular flaps (lateral or anteroposterior) ; in the lower part of the thigh, by anteroposterior muscular flaps; in the middle of the thigh, by one tegumentary flap raised from the anterior surface of the limb. The oval method will be found particularly applicable to amputations at certain articulations, while the method of Teale, which has not been exten- sively practised in this country, will give good results in amputations of the leg and forearm where the injury or disease has invaded a limb more extensively on one side than on the other. Ligation of Vessels. — When the amputation proper is completed, the entire attention of the operator must at once be directed toward permanently controlling the hemorrhage. For this purpose it is best to grasp the divided blood-vessels, one after another, as they are seen, with hemostatic forceps, which are allowed to remain in the wound until all the vessels are thus held. This accomplished, the vessels are separately tied with catgut. The ligatures are then cut short. Veins should be tied to avert the development of a general infection out of a possible local infection. As a rule, not more than from four to six arteries will require ligation in all amputations, except those of the hip and shoulder, although long- standing disease (large neoplasms or preexisting occlusion of the main artery) may have multiplied the number of vessels requiring ligation. Here, as in ordinary wounds, at least the larger arteries should be carefully exposed before the ligature is applied. In the smaller vessels, where their exposure would entail an unnecessary loss of time, portions of the tissues in which they are embedded may safely be included in the ligature by passing this with a needle behind the bleeding vessel. The question has for a long time been discussed as to whether the veins should be tied. There can be no question but that the ligature of the divided veins removes a common source of secondary hemorrhage, and materially reduces that immediately following the removal of the Esmarch bandage. The opposition to the ligation of veins in amputations has been mainly based upon the fear of exciting an as- cending phlebitis and of giving rise to embolic proc- esses. That these fears are utterly groundless has been conclusively demonstrated. " Of forty cases of ligation of the internal jugular vein, death was fairly ascribable to the ligature in only four, all due to secondary hemorrhage coming on about the time of the separation of the thread. In not a single instance was diffused phlebitis excited. In twenty cases of ligation of the external jugular vein, and fifteen of the axillary, additional evidence of the safety of ligation of veins is recorded." The most troublesome hemor- rhage is the parenchymatous oozing which supervenes when the Esmarch bandage is removed. How- to contend against this has already been discussed (see above). It is proper to add, however, that in every case the application of an abundance of hot water is of unquestionable value. When the oozing from the divided end of the bone is not checked by this, the medullary canal may be temporarily plugged with clean white wax, or with sterile gauze. The accurate closure of the wound and pressure upon it by a well-applied bandage are among the best means of checking the capillary hemorrhage. When it is necessary to resort to this means, a large gauze pad is firmly pressed against the wound and retained until the sutures are passed. As the sutures are tightened the pad is gradually withdrawn while an assistant tightly presses the wound surfaces against each other. In large amputation wounds, the size can be greatly reduced by buried continuous catgut sutures which bring the divided muscles close together. Sutures thus applied in purse-string fashion or in tiers help to cover the bone and to prevent the formation of dead intermuscular spares. After-Treatment. — It is beyond the scope of this article to enter into an extended discussion of the various methods of treatment of wounds, although in hardly any other class of wounds are the good or evil results so clearly attributable to the manner of treat- ment adopted. The question at once presents itself whether the surgeon will pursue a course which will reasonably assure a total, or at least partial primary agglutination of the wound, or whether he will avoid the dangers of retention and decomposition of the secretion of the wound by treating this openly, thus expecting its closure by the slower process of granula- tion. The latter plan, which is now known as the "open method," was first enunciated by Vezin. Bartscher, and Burow 5 in Germany and disseminated in this country by the late Dr. James R. Wood. When this method of treatment is adopted, sutures adhesive straps, etc., are entirely dispensed with, the stump being comfortably placed on a pillow or pad, and the wound freely exposed to the air. A mass of absorbent cotton is placed underneath the stump to catch the discharges from it. Twice daily the wound is irrigated with an antiseptic solution, usually of carbolic acid, until at the termination of the first week, when the process of granulation has been thor- oughly established, the edges of the wound are ap- proximated by adhesive strips, care being taken that retention does not occur. The manifest advantage of the "open method" of treating amputation wounds is in the ready outlet which is given to the secretions. Their decomposition in the wound is thoroughly prevented, and the chief factor of septic absorption is thus avoided. However admirable the results which have been obtained from it, the length of time required for the closure of the wound (six to twelve weeks) militates against its general adoption. While incomparably better than the older methods of tightly closing the wound regardless of proper drain- age, the open treatment of wounds has subserved its purpose, and has yielded to the superior advantages of the aseptic method, which strives to obtain the ideal of the surgeon in the treatment of wounds, viz., primary union. The open treatment of amputation wounds has been therefore properly relegated to those cases in which the surgeon is convinced that, from the condition of the parts in which the operation has been made, or from the general condition of the patient, primary union cannot, take place. When a doubt exists as to the certainty of primary union, sutures should be passed both deeply and superficially and left untied. The wound itself is packed lightly with sterile gauze. If, at the end of forty-eight or seventy-two hours, there is no evidence of septic infection, the gauze may be removed and the sutures closed with prospect of securing union without suppuration. When, on the other hand, primary union is aimed for, all drainage is to be dispensed with unless there is considerable oozing. The rubber drainage tube formerly extensively used is gradually being replaced by a narrow wick of sterile gauze drain in rubber tissue, or a strand of silkworm gut passed through the angle of the wound from the immediate vicinity of the divided bone. This can be removed on the third or fourth day, or, if there is no evidence of infection, may be allowed to remain until the first dressing is changed, after a week or ten days. When, as in the case of amputation of I he heel (Syme), there is danger of the formation of a dead space, one of the flaps can be perforated in such a manner as to prevent pocketing of wound secret ion. Although an advocate of limiting drainage as far OS possible, the writer believes it should be resorted to in every case in which oozing has not been entirely stopped by the time the sutures are read}' to be tied. Primary union is often prevented by the accummula- tion of bloody serum, which mechanically separates surfaces which ought to be held in apposition. An amputation wound is to be closed by three or 274 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation four deep sutures, which should include the entire thickness of the muscles on each side of the divided bone, they should be of fine cupper wire or silk- worm put. The superficial sutures or skin clamps should he placed al distances of about one-third of an inch from one another. The dressing of the wound follows. The amount of material used should be ample and it should be so applied that pressure will tend to keep the wound sur- s in apposition. Unless a moist dressing is ued advisable because a doubt as to the asepsis -. a dry dressing should always be used with pulous attention to surgical cleanliness. Even amputation wounds, as those of the thigh, hip, or shoulder, will generally heal under one or two dressings. As in other operations, the dressing should kllowed to remain for at least a week or ten days. Should there be a slight oozing, a change of dressing i~ imperative. The stump should always be main- tained in an easy position on a pillow or a well-padded posterior splint. It is usually advisable to elevate this to a degree sufficient to faciliate the return of blood through the veins. Postoperative oozing can thereby be best prevented. After amputations in which the asepsis has been suc- cessfully carried out, even the largest wounds will heal entirely by first intention. The dissimilarity of tissues which are often brought in contact with one another in an amputation wound, and which were formerly supposed to preclude the possi- bility of immediate union, is no obstacle to the achievement of this result. Of greater importance are the novel relations of the blood-vessels to one another. The circulation in the veins of the stump has lost the vis a tergo so essential to the proper per- formance of their function, while the smaller arteries are distended with blood in consequence of the in- terrupted circulation in the main vessel. It is for this reason that a marked edema and congestion will often manifest themselves in the stump. Unless infection has occurred, these manifestations will disappear in three or four days. In whatever manner the wound heals, certain marked changes will occur in the stump. The muscular tissue undergoes atrophic changes, its fibrous elements becoming firmly adherent to the end of the bone. This itself gradually decreases in size, the end becoming rounded off and often covered by a rounded osteophyte formed from the periosteum or from the granulations springing from the medullary canal. Where two bones are present, an irregular osseous bridge not infrequently unites them (Gueter- bock 6 ). As a rule, the end of the bone is intimately united to the soft parts covering it, although at times a bursa is developed between them. The ligated vessels are converted into firm fibrous cords for a varying dis- tance and are reduced in size, not only in the stump but also in the entire limb. Thus, in amputations of the leg, the artery and vein are reduced over one-half in size as high as the inferior vena cava and the bifurcation of the aorta. The divided nerves lose their nervous elements by atrophy, while their connective-tissue components increase in number until their extremities "ften expanded and bulbous, thus forming false neuromata. Complications. — Pain and muscular spasm maybe said to be present to a greater or less degree after every major amputation. They usually supervene soon after the patient regains consciousness, and may develop to a distressing severity, particularly in persons of a nervous and irritable disposition. For the relief of these symptoms hypodermatic injections of morphine act most promptly. The jactitations of the -tump are most successfully overcome by lightly fastening the stump with a few turns of a bandage to a well-padded posterior splint. A very slight reaction may be said to be necessary to the process of repair. When infection has taken place, the evidences air speedily seen in the wound. It may lead to more or less extensive suppuration, to a limited sloughing, or to gangrene of the -lump. When such severe inflammation attacks the wound, the stump becomes exquisitely sensitive and hot, and i Lines a dusky red and glistening appearance. The discharges from the wound arc scant and offen- sive, while the elevated temperature aid hard and rapid pulse sufficiently indicate 'lie constitutional dist urbancc. When the inflammatory proci along the intermuscular spaces the limb becomes sensitive to the touch, and swollen for a considerable distance above the seat of operation. When suppu- ration ensues all may yet be well, (in the other hand, the exudation into the tissues may develop in proportions incompatible with the vitality of the parts, when extensive sloughing, and even gangrene ..t i he entire stump, may result. The treatment of these conditions must be con- ducted upon established principles. Locally nothing answers so excellent a purpose as measures which relieve the tension. Stitches, when too tight, mii-i be removed, and as soon as a suspicion of purulent accumulation is aroused, free incisions are to be made. When such extensive suppuration has supervened it is advisable to remove all constricting dressing, and to treat the wound by the open method, removing sloughs as fast as they are formed. Frequent irri- gations with sublimate solutions and hydrogen di- oxide are now indicated. As a dressing the balsam of Peru (ten per cent.) in castor oil applied on strips of gauze will do away with the necessity of drainage. As an especially dangerous seat of inflammation the medullary canal of the bone must be referred to. Periostitis and osteomyelitis are particularly prone to follow amputations made for gunshot injuries. It usually manifests itself during the first week after the operation by a brownish or greenish appearance of the medulla, the bone appearing dull and devi- talized, while the periosteum is detached from its surface. The pain is usually very severe, and associated with it are the well-known symptoms of systemic infection, i.e. rigors elevated and irregular temperatures, diminished secretion of the kidneys, and a dry and thickly coated tongue. Not only does this condition lead to extensive necrosis when recovery ensues, but death may result from general- ized sepsis. The only measures that offer any hope for this condition are to scoop out the bone cavity with a sharp spoon, and if this prove unavailing, to resort to a second amputation at the nearest joint. However desperate this procedure may be, a very- large number of cases have been reported in which lives have been saved which, without it, would have been inevitably lost. As a sequel of moderate inflammation of bone, necrosis of its extremity is not infrequently encoun- tered. This may result from devitalizing of the bone from excessive heat generated by the improper use of the saw. If the necrosis be limited to the divided end, this condition does not interfere with the primary union of the greater part of the wound. The exis- tence of such a superficial sequestrum can be deemed probable when, after the permanent closure of the wound, a fistulous tract continues to discharge. Its actual presence can always be recognized by the cautious use of a probe or by the x-ray. When the sequestrum is of larger proportions, numerous fistu- lous openings will usually be found in the soft parts, which are then more or less adherent everywhere to the bone. The treatment of this condition must In- palliative until nature has completely separated the sequestrum, when it can ordinarily be removed with little difficulty by laying the fistulse freely open. When the sequestrum is large, it occasionally becomes necessary to resort to a formal sequestrotomy for its removal. In a very small proportion of cases the irri- tation consequent upon the long-standing discharges 275 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES from the necrosis of the bone gives rise to epithelioma for the relief of which a second amputation is usually necessary. One of the most dreaded complications of an ampu- tation is hemorrhage. It may supervene within a few hours after the completion of the dressing, or as late as the third or fourth week. The sources of early and late hemorrhages after amputations differ materially. The former arise from small arteries or veins that have escaped ligation, from arteries divided above the ligature, or from the divided capillaries of the muscles. This condition is readily recognized by the staining of the dressing, the distended appearance of the stump, and the flowing of blood from a number of places where the edges of the wound have been separated. The rapid distention of the stump and the bright hue of the blood which is discharged at once indicate the arterial source of the hemorrhage. The darker appearance of the blood and its appearance in a sluggish stream sufficiently indicate its venous origin. Blood oozing from a hematoma is always dark. When the hemorrhage is slight, and particularly if it can be recognized as venous, elevation of the limb and the application of ice may suffice for its control. When it becomes evident that such simple measures are futile, the wound must be reopened, the coagula removed, and the bleeding vessel found and ligated. \\ hen it is found that the hemorrhage has come from the medullary canal, this must be treated in the manner already described. The hemorrhages which supervene during the second week, or even later, usually result from the erosion of a vessel wall weak from sclerotic changes at the time of operation, or from wound infection and softening of the thrombus. By cutting short both ends of the ligature the neces- sity for the "cutting through" of the latter is done away with, and at least one important factor in the causation of late hemorrhages is thus removed. For the relief of late hemorrhages, compression of the artery by a compress and firm bandage should first be tried. When this proves unsuccessful, pressure should be made at different points of the main artery to determine the point nearest the stump where the hemorrhage can be controlled. Here the artery is to be exposed and ligated, or, what seems to be preferred by most recent writers, it may be included in the pressure of an acupressure needle. Reopening of the wound and direct treatment of the bleeding vessel is usually successful although in rare cases it may become necessary to resort to reamputation. A peculiar and very rare condition of the stump is the development in it of a dilatation of the blood- vessels, commonly in the form of an aneurysmal varix. Cases of this nature have been recorded by Cadge of Norwich, England, by Gross, and by Agnew. Whereas, in some cases of this kind, operative treatment would not be called for, in others it may become directly indicated. Thus, in the case of Gross, 7 ligation of the femoral was deemed necessary. The operation resulted fatally, from secondary hemor- rhage, on the sixth day. The form of the stump very frequently gives rise to considerable annoyance and suffering. A healthy stump should present a nicely rounded outline, with tin- bones hidden beneath and away from the cicatrix. From a variety of causes this normal appearance of the stump may give place to prominence of the bone, retraction and ulceration of the soft parts covering it, and uselessness of the part for locomotion. Such an abnormal condition is commonly known as the "conical" or "sugar-loaf" stump. It may result from an insufficiency of flap, from inordinate retrac- tion of the soft parte, or from gangrene of the integu- ment alone. It is a condition which is more likely to follow the circular and tegumentary flap ampu- tations, although with ordinary precautions it would seem that amputations in healthy tissues should not result in a badly formed stump. When this condition 276 does result, nevertheless, its treatment must vary according to the extent of the deformity. When from an insufficiency of flap or excessive retraction of the soft parts, the end of the bone assumes a too prominent position, the flaps can be drawn down by appropriate bandaging, from above downward; or, by the aid of adhesive straps and weights, extension may be made in such a way as to cover the end of the prominent bone with integument (Fig. 123). When, notwithstanding these measures, the proper relation between bone and soft parts cannot be brought about, nothing remains but to enlarge the wound, remove the periosteum from the bone, and divide this several inches above the level of the first section. It is unnecessary to defer this until the first wound has cicatrized. In extreme cases of conical stump reamputation will be indicated. It can be more highly recommended since reamputation is not often followed by bad results. Mr. Bryant refers to a very interesting condition of amputation stumps in children, in whom the development of conical stumps Fig. 123. may be in a measure expected, since, in the process of growth, the bone appears to develop more rapidly. In the case of a boy whose leg was amputated, he found it necessary on two occasions, at intervals of three years, to remove two pieces of bone at least an inch long. Neuroses of the stump are among the most intract- able of its diseases. They may appear in the form of severe neuralgias, or in the form of spasmodic muscu- lar contractions. The former condition usually depends upon an adherence of the divided nerves to the bone or the cicatrix, while in exceptional cases it results from the bulbous enlargement of the extrem- ities of the nerve. For the relief of the former condition, subcutaneous division of the adherent cicatrix must be practised. Where neuromata can be felt, these are to be removed; when, from the number of these enlargements or from their deep positions, this procedure is impracticable, nothing short of a reamputation will give relief. Continuous jactitations, or "chorea" of the stump, as it might be termed (Gross), is very rarely encountered. It is more prone to develop in the thigh than elsewhere. The stump, when thus affected, is the seat of a constant tremor, often sufficiently active to be noticed when the limb is covered. In a case of this character which I saw two years ago, and which involved the thigh in an otherwise healthy subject, the spasms continued, notwithstanding all efforts to allay them. The most efficient measure was the deep injection of ether, which would relieve the spasm for about two weeks at a time, when the injection had to be repeated. Prognosis and Mortality. — In estimating the inherent dangers of the operation, we must take into consideration only those cases in which the individuals operated on were — aside from the lesion which neces- sitated the operation — in the enjoyment of compara- tively good health. As it is incorrect to attribute the immense mortality of tracheotomy for diphther- itic croup to an operation which, if performed for the removal of foreign bodies, is almost alwaj's successful, so it is manifestly improper to attribute most deaths after amputation to the operation itself. A compila- reference handbook of the medical sciences Amputation tioii of the amputations of "expediency," made in Guy's Hospital, indicates a mortality of 26.8 per criii. If we remember, however, thai these statistics of Bryant and Golding Bird include amputations made for neoplasms, and that the most valuable methods of after-treatment were at that time not employed in the hospital in question, tliis percentage must be misleading as to the inherent dangers of amputations. That the mortality of the operation under favorable circumstances can be greatly reduced front the percen age aBovo given can be easily demonstrated. Thus, of 716 late and pathological amputations collected by Sir James V. Simpson from smaller hospitals and private practitioners of Scotland and England, only seventy-four, or 10.3 per cent., died. Of 100 amputations (including thirty-nine of the thigh) made by Brims, only twelve terminated fatally. According to the latest statistics of Bruns, of 204 major amputations two per cent, only died. Finally, of 187 amputations made by Volkmann for onlj seven succumbed (three per cent.). This number includes seventy-four amputations of the thigh with only two deaths. statistics can hardly be improved upon, although we are in need of carefully compiled data of amputations performed with modern aseptic pre- ■ion. Except for the amputations near or at tin- hip, or of a limb and part of the shoulder girdle or ilium, the mortality uf amputations is practically nil. One must exclude, of course, such cases as diabetic gangrene or acute septic invasions. Unhappily these statistics are largely at variance with those gathered either from large hospital- or from the battlefield. Thus, of 500 larger amputations for all causes collected by Malgaigne in the hospitals of Paris, 299 ended fatally, the mortality being fifty- three per cent. The fatality attending amputations by English surgeons in the Crimean campaign is represented by 420 operations, with 169 deaths (39.6 per cent.), while the figures of the French surgeons during that war are 4,390 amputations, with 3,218 deaths, giving the appalling mortality of seventy-three per cent. Compared with such results those obtained during the War of the Rebellion show a most decided improvement. Of 29,980 ampu- > is, the result was determined in 28,261; of these, 20,802 recovered. There were 7,4.59 deaths, tints yielding a mortality of 26.3 per cent. The most complete recent statistics of amputations for gunshot injur}' show only a moderate improvement over those obtained by the older methods. Thus the irt of Surgeon General Stevenson on the South African War shows that of 134 major amputations, only seventy per cent, recovered. This was largely- due to the fact that at the time of the operation, the patients were already septic. John F. Erdmann, 8 in 1S9.5, tabulated the statistics of amputation performed in the leading hospitals in York, done during the decade preceding. Of 709 major amputations 109, or fifteen per cent., died. Page,* in 1S95, collected 712 major amputations from the infirmary, Newcastle-upon-Tyne, of which sixty- one died, giving a mortality of 8.5 per cent. In thirty of the fatal cases death resulted from shock and loss of blood. Forty years before, Fenwick had tabulated 225 amputations done in the same infirmary with a mortality of fifty-four, or twenty-four per cent. Of 163 amputations done in the Cincinnati Hospital during the decade preceding January 1, 1000, nineteen terminated fatally. The gross mortality of the series was 12.7 per cent. From the clinic of Bruns 10 comes the remarkable record of eighty-one ampu- tations of the leg without a death. An examination of all statistics will show that the mortality of major amputations is gradually being reduced. If the cases are subtracted in which death resulted from shock and the loss of blood, the mortality of all major amputations will be reduced to about four per eeni., as has been the case with the statistics published By Estes. It is not the least important achievement of Mal- gaigne to have directed the attention of -urge. ins to the chief causes which modify the; prognosis in indi- vidual cases of amputation, and how, therefore, statistics must vary according to certain now well- known conditions under which they are collated. In a somewhat similar direction were the investiga- tions of Simpson. The conditions which influence the prognosis of amputations will now be considered in the order of their importance. Age. — The mortalitj of amputations is determined more By age than By any other one factor, since they betterborne in childhood and adolescence than later in life. Malgaigne was the first to point this out By the tabulation of 560 i :a es in which the mortality steadily increased with the age of the patients. Amputations between the ages of five and fifteen years yielded a mortality of thirty-three per cent., those Between fifty and sixty-five one of , 1.1 per nut. Similar investigations have Been made By Callender, Holmes, Bryant, and Golding Bird in England, and By Morton and Ashhursf in this country. The last- mentioned author combined the statistics from various sources, and, after the manner of Mr. Holmes, he divided life into three periods of twenty years each. The total number of cases thus tabulated is sum- marized as follows: Table I. — Percentage of Mortality at Different Ages. Whole number of Mortality below 20 years. Mortality between 20 and 40. Mortality over 40 years. General death rate. 2,619 16.7 30.1 43.4 29.4 Table II. — Percentage of Mortalitt Before and After Thirty Years of Age. Whole number of ca-ts. Mortality Mortality General death below 30 years, above 30 years. rate. 1,805 19.2 37.4 26.7 The comparatively excellent results after amputa- tions in children must Be attributed to the rapidity with which even large wounds unite in them, to the resistance which their ordinarily unvitiated constitu- tions offer to septic processes, and to their freedom from visceral complications. The ease with which even large amputations are supported in childhood was particularly impressed on the mind of the writer By the case of a lad of seven, in whom he had ampu- tated Below the shoulder for railway injury. Because he was not given the freedom of the ward, the boy escaped from the hospital (Good Samaritan, in Cincinnati) on the eighth day after the operation. The wound had healed per primam. The very unfavorable results which follow amputa- tions in advanced life are readily- accounted for by the reduced vitality of the system at large. By the imper- fect nutrition of the stump from impaired integrity of the blood-vessels, and By the rapidity with which these patients succumb to septic infection, or post- operative pneumonia. It is extremely probable that if the latter could be prevented the marked influence of advanced life on the results of amputations would be materially lessened. Thus of sixty-one uncompli- cated amputations made by Volkmann. in persons over fifty, only 4.S per cent. died. Among these was a successful amputation of the thigh for injury in a man eighty-four years of age. 277 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Seat of Operation. — The danger of an amputation always increases with the size of the wound and its proximity to the trunk — amputations of the lower extremity yielding a greater mortality than those of the upper. Since about thirty-two per cent, of the deaths following amputations are directly attributable to the combined shock and hemorrhage consequent upon the injury and the operation, it is easily under- stood why the mortality varies in the manner indi- cated. The dangers of septic infection also increase with the size of the wound, and when amputation wounds fail to unite by primary union, death often results from the exhaustion consequent upon pro- tracted suppuration. The situation at which the bone is divided also materially influences the result. The opening of the medullary cavity of a large bone like the femur or tibia is more apt to be followed by osteomyelitis and its consequences than is the division of the bone through its articular end. This is well shown by a comparison of the results of amputation through the lower third of the thigh and through the femoral condyles, the former operation yielding a mortality of thirty-nine per cent, against twenty-nine per cent, of the latter. The ratio of deaths following amputations for injury and disease in different parts of the body is well illustrated in a subjoined table which is based upon large hospital reports issued from 1S64 to Ins I. For exceptional operations (hip-joint and elbow) reports of cases from private practice were included. This doubtless explains the apparently greater mor- tality of amputation of the thigh than of the hip, since relatively more successful than unsuccessful cases are thus recorded. Nature of Lesions. — Very potent in its influence on the results of amputations are the causes for which they are made. When the operation is resorted to in an individual who, while in perfect health, has received a severe injury from which he has probably lost a considerable amount of blood, the prognosis is much less favorable than when it is made for disease. This applies particularly to amputations after railway injuries and traumata inflicted by heavy machinery. The shock and hemorrhage are very often so severe Table III. (From Max Schede). Amputations for Amputations for lnjury. disease. o :•> j o =■>.! — . t. . $ 2 S z - r. H go S j= 3 -O 1 i o S B2 % Si 3 2 3-B £ 05 Z z Z z Amputation — 55 39 70.9 153 65 42.6 of thigh, upper 73 57 78.0 42 15 35.7 third. of thigh, middle 67 50 74.6 137 55 10.1 third. of thigh, lower 149 71 50.0 205 64 31.0 third. of thigh, through 136 44 32.3 79 20 25.4 condyles. of thigh, locality 1.3S4 664 48.0 2,494 S17 32.7 not specified. 314 130 103 54 32.8, 41.5 123 17S 30 44 24.4 of leg, upper and 24.7 middle third. of leg, lower third. 33 3 9.1 128 19 14.0 of leg, locality not 1,956 785 40.0 1,695 215 12.7 specified. of foot, partial.. . 223 45 20.2 562 70 12.4 at shoulder- joint. 271 116 42.3 IIS 33 28 1,167 23 364 6 31.2 26.0 441 8 SI 1 18.4 at elbow-joint. . . . 12.5 1,316 143 10.8 506 62 12.2 199 337 5 6 L> . 5 1.8 27 329 of fingers and 6 1.8 toes. It will be seen from the table given below that the statistics indicate with remarkable uniformity the greater mortality of amputations when made for injury than when made for disease. The explanation generally offered for this feature of the prognosis of amputations is that patients who have for a long time been subjected to suppurative processes (necrosis, TABLE IV. Amputations for injury. Amputations for disease. Total Amputations. Authority. Number of cases. Number of deaths. Mortality, per cent. Number of cases. Number of deaths. Mortality, per cent. Number of cases. Number of deaths. Mortality, per cent. 1S2 4 17 846 106 1 1 1 28 130 72 1S6 388 355 159 115 117 201 202 57 58 21 24 24 77 126 84 72 33 64 45 24 54 40 75 19 33 41 32 2 1 46 29 378 679 524 58 94 52 1S7 2S 371 338 305 409 424 1S2 147 102 IS 32 25 7 4 73 40 48 99 55 48 2° 19 31 33 4S 3 14 19 12 16 24 13 560 1.126 1,370 164 238 SO 317 100 557 726 660 568 539 299 34S 304 75 90 46 31 28 150 166 132 171 88 53 31 22 Billroth (1860-67) . . 46 38 57 9 + 28 27 23 20 30 16 Total.. . 3.158 1,096 34.7 3,847 832 21.6 7,005 1,928 27.5 that death results within a few hours after the opera- tion. The prejudicial effect of a trauma on the results "f amputations is still further enhanced if the subject is addicted to intemperate habits. This was well illustrated in the Cincinnati riots in 1SS4. Those injured were for the timst part more or less under the influence id' alcohol when wounded, and four-fifths of those on whom amputations were made succumbed. caries, etc.), are so inured to suffering that they bear the shock of an operation comparatively well, and that they are less prone to septic infections which are so often the immediate cause of death titter amputa- tions for trauma. The correctness of this view is substantiated by the fact that about seventy-five per cent, of so-called pathological amputations are made for chronic inflammatory conditions of either 278 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation bones or joints, and that under these circumstances tin' soft parts are usually more or less atrophied, and yel at the same time densely infiltrated with a connec- tive-tissue growth which, when divided in an opera- tion, presents a barrier to the absorption of deleterious elements. It is noteworthy, as Mr. Bryant has pointed out, that this infiltration of the soft parts does not necessarily interfere with the ready union of the wound. While amputations for chronic affections of the nature indicated terminate fatally in only four- teen per cent, of the cases, those made for deformity and neoplasms present a mortality of 26. S per cent, and forty-six per cent, respectively (Golding Bird and S pence). Tables V. and VI., while they show the great reduction in the mortality of amputations in general, Mill demonstrate the greater mortality of operations done for trauma. That the difference is not so marked in my own table (V.) is due to the fact that many of the pathological amputations were made for senile gangrene. Tadle V. — Major Amputations Done at the Cincinnati Hos- pital from January 1, 1890, to January 1, 1900. Injury. Disease. •6 u o > o a -3 3 O H c Hi o u a •6 > a Ci ~6 0) s o o o Leg 54 4 11 3 5 57 4 16 5.2 31.3 22 2 17 1 2 1 3 24 3 20 1 8.3 3.3 nigh Hip 1.5 Wrist 2 11 1 2 12 Elbow S.3 3 *3 11 2 4 11 6 3 1 3 1 Total 95 13 108 13.7 19 6 55 10.9 * One multiple injury. Table VI. — Amputations Done During Twelve Years Prior to 1895, Newcastle-on-Tyne. (Page.) ta 3 > o s u 1) s 3 > o 5 fc Ph 55 0) Ph 13 7 6 46 tation, Hip-joint 6 3 3 50 23 14 9 3.9 Thigh 52 39 13 25 1.31 141 10 6.4 7 76 7 69 2 70 2 67 7 9.2 3 4.2 26 2.". 1 3.8 [22 120 2 1.6 Shoulder 17 16 1 5.8 15 14 1 6.6 37 31 3 8.1 IS 17 1 5.5 36 7 35 7 1 2.S 31 31 Total 277 212 35 12.6 435 109 26. 5.9 Multiple Amputations. — While it is comparatively rare that disease or injury affects more than one extremity in a degree sufficient to warrant double amputations, these are nevertheless occasionally re- quired. It is self-evident that they are of the gravest importance and present a most unfavorable prognosis, on account of the shock associated with the injury. Of twenty-eight double amputations made in the West- ern Pennsylvania Hospital, twenty-seven were for rail- road accidents and fifteen of the patients died. The fact that eleven of the deaths occurred in the first forty- eight hours shows that they were due rather to the in- juries than to the amputations. Of thirteen multiple amputations done for injury at the .Newcastle Infirmary six, or forty-six per cent., died. When multiple amputations are made for disease, which is in about ten per cent, of all cases, they are usually for frost-bite. Table VII. — Multiple Amputations in Military Practice. "5 | i EJ > o ~. 8 *D .5 2j si 3 " a U ~ * 2 „° a Ph Both amputations in the 17 31 16 34 upper extremity. One amputation in upper, 43 21 21 1 50 one in lower extremity. Both amputations in lower S2 31 50 1 61.7 extremity. Total 172 83 87 2 50.5 Tarle VIII. — Multiple Amputations in Civil Practice. Number of .■uses. Recovered. Died. .Mortality, per cent. Thighs 18 21 5 7 42 11 12 9 15 3 9 2 4 20 6 10 6 11 15 12 3 3 22 5 2 3 4 83 Thigh and forearm.. . . 57 60 43 52 45 Foot and foot Forearm and forearm. 16 33 27 Total 140 71 69 49 The mortality attending multiple amputations, it will be seen from the preceding tables, is about fifty per cent., amputations through the lower extremities presenting a greater fatality than those of the upper. The first table illustrates the mortality of these am- putations in military practice. The second table, made up from German, English, and American re- ports, shows the relative frequency and fatality of multiple amputations as they are made in different parts of the body. When the necessity for multiple amputations arises, the question must be considered whether they shall be made at the same time, when they are called syn- chronous amputations, or whether a longer or shorter interval shall intervene between them. In these cases, as in amputations generally, no definite rules can be formulated. In cases of trauma it is generally advisable to make both amputations at the same time, removing the larger member first, but deferring the closure of the wound until both amputations are completed. If, after the first operation, the condition of the patient is such as to preclude the possibility of recovery if the second is performed at once, the less injured member must bo treated as if the injury sustained by it were of a less degree of severity and justified an attempt at conservatism. In cases of disease affecting several extremities (frost-bite, white swelling, etc.), it is generally better to observe a, sufficient interval between the operations to permit the constitution to rally from the first before the second amputation is made. In these cases the danger of septic infection from the limb that is spared is not as great as in cases of traumatic origin. 279 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Even triple and quadruple amputations are occasionally performed with success. In a case of railway accident, Dr. G. Koehler, of Schuylkill Haven, Pa., in 1S67, removed simultaneously both legs and one arm from a lad thirteen years of age, recovery taking place. Professor Stone, of New Orleans, had a similar case in a man of thirty, the subject of a railway accident. According to Professor Agnew, successful triple amputations were made in York, Pa., in 1868, and Rochard reported to the Academy the case of DeLeseleuc of Brest, who had successfully amputated a thigh, leg, and arm in a man the subject of trauma. Quadruple amputations, usually made for frost-bite, have been successful in the cases of Muller, of the United States army, Begg, of Dundee, and Cham- penois, of the French army. Other cases are referred to by Morand, Longmore, and Southam. Larrey mentions two cases, one of which, the case of a soldier who had all his extremities removed by heavy ord- nance, he had seen in the "Invalides." The other case, which he had seen in Algiers, was that of an Arab twelve j'ears of age who had intentionally placed himself on the track in such a position that a passing train mangled both hands and both feet. Still another successful quadruple amputation for frost-bite has recently been recorded by Tremaine. Individual Amputations. Amputation op the Fingers. — When the pha- langes of the fingers or thumbs are the seat of incur- able disease or of severe injury, amputation often becomes necessary. It is well to remember that if the bone of the distal phalanx alone is affected, its natural exfoliation should be awaited, when the soft parts can often be preserved, to the great advantage of the patient. Particularly in the thumb and index finger is it necessary to save as much as possible. In the third and fourth fingers amputation should not be practised at the second joint, since the pres- ervation of the proximal phalanx leaves a part that is ungainly and does not add to the usefulness of the hand. When a portion of a finger requires removal the operation may be practised either at a joint or in the continuity of a phalanx. In both cases it is important to remember that when the finger is flexed the articulations are below the prominences made by the knuckles, the distal, middle, and proximal articu- lations being respectively one-sixth, one-fourth, and one-third of an inch below the most prominent lines of the joints. It must also be borne in mind that strong lateral ligaments prevent, until they are divided, the complete exposure of articular surfaces (Fig. 124). When the amputation is to be made at the joint, it can be most ex- peditiously executed in the following manner: The hand being held in the prone position, the tip of the finger encased in a piece of gauze is firmly seized by the oper- ator and flexed. With a long and narrow knife an incision is made from side to side over the dorsal sur- face. By this the joint is at once opened. With two rapid strokes of the point of the knife the lateral ligaments are next severed. The blade of the knife, with edge directed downward, is then placed behind the flexor surface of the phalanx to be removed, from the soft parts of which a well-rounded flap, is to be cut from within outward by a sawing movement. The wound pre- sents the appearance shown in Fig. 125. Only when there is an insufficiency of flap is it proper to remove the head of the proximal bone. The disarticulation of a phalanx can also be effected by transfixion: the Fig. 124. hand being held in a supine position and the finger extended, the latter is transfixed on the palmar side of the bone, just below the fold of the joint; a palmar flap of sufficient length is then made. The flap being held out of the way, the joint is made prominent by hyperextension and opened. The soft parts on the dorsal surface of the joint are then divided by a single sweep of the knife. In amputations of the fingers, the soft parts of the palmar aspect are always preferable for a flap, since the cicatrix is then pro- tected from pressure. Where they cannot be utilized, a dorsal flap can be made, either by transfixion or, what is preferable, by cutting from without. Lateral flaps, single or double, can like- wise be utilized in this amputation. In amputations in the continuity of a phalanx the flap may be cut from the palmar aspect by a transfixion, the dorsal surface being divided by a transverse incision, or a second flap may be formed. The circular operation, with longitudinal lateral cuts, may likewise be successfully practised in this position. After the division of the soft parts, the bone must be divided with a metacarpal saw or the cutting forceps. In all amputations of the fingers two digital arteries usually "spirt." Their ligation is unnecessary; the approximation of the wound surfaces generally suffices for their closure. Amputation of an entire finger at the metacarpo- phalangeal joint can be readily accomplished as follows: The adjacent fingers being held aside by an assistant, the operator with his back to the patient grasps the finger to be removed with the left hand and extends it sufficiently to see its palmar surface. A narrow knife being introduced from the right side divides the soft parts on the palmar surface on a level with the extended interdigital web. The incision is then carried around the right side of the finger (Fig. 120, Esmarch) in a slight curve into the dorsal surface Fig. 126. of the head of the metacarpal bone. The knife is then carried around the left side of the finger in the same manner, the ends of the first incision being thus joined. The tendons, lateral ligaments, and capsule being successively divided, the disarticulation ia completed and a heart-shaped wound left. The margins of this wound come accurately into contact, when the remaining fingers are approximated to one another. When comeliness of the hand is valued more than strength, it is best to remove the head of the metacarpal bone with cutting forceps (Fig. 127), since its preservation usually leaves an unsightly prominence. In persons who do manual labor its 280 reffkexcf handbook of tiik medical sciences Amputation removal should be avoided, since it would materially lessen the strength of the hand. The incisions for disarticulations of the thumb, index and little fingers may often l>e advantageously modified in such a manner as to make two lateral llaps, the longer of which is on the free side of the tiger, the shorter being made on the side of the tnterdigital web. To preserve the symmetry of the hand, t he heads of the Second and fifth metacarpal bones should always be removed by an oblique section when the index and little fingers are amputated. \\ hen I no or more fingers are to be removed, it can easily be done by making two convex flaps, one on the dorsal and the other on the palmar aspect of the hand, the latter being given the greater length. A flap may likewise be taken from the side of one finger, or reel angular flaps from the opposite surfaces of the fingers that are farthest from each other. In amputations of a number of finger- it is generally best to remove Fia. 127. each finger sepa- rately, since un- issary sacrifices for thesakeof brilliancy will thereby be avoided and a better result be obtained. When, in consequence of accident or disease, the metacarpal bone must be removed with the finger, the incisions are like those for the removal of an entire finger, only that the dorsal cut must be continued upward toward the wrist for a varying distance, and that the incision around the root of a finger is to be made above the interdigital web. The extensor tendons being divided as high as possible, and the bone separated from its muscular attachments, this is divided with cutting forceps near its articular extremity or entirely enucle- ated. When the surgeon has the option, the former practice should be preferred, to avoid opening the articulations of the wrist. Exceptions can be made in the first and fifth metacarpal bones, which, having individual synovial sacs, may be removed without the danger of producing extensive inflammation of the wrist. Amputation of the entire thumb should rarely be practised, for every portion of it that can be saved is of value for opposition to the fin- gers. When it becomes necessary to remove the thumb with its meta- carpal bone, it is best accomplished by the oval method. The point of a knife should be entered above its articulation with the carpus, and a triangular incision (Fig. 12S) made along its radial aspect, the sides of the triangle diverging from each other as they approach the head of Fig. 128 the metacarpal bone and becoming continuous with each other in the web and index finger. The muscles being detached and the extensor tendons divided, disarticulation is readily effected by forcibly' extending the thumb toward the radial side and severing the ligaments. In disarticulating, the edge of the knife should be kept close to the base of the bone, lest the joint between the second meta- carpal and trapezium, and through it the remaining Carpal joints, be opened. After this operation a linear cicatrix remains. The most expeditious method <>i amputating the thumb yet devised is that of Walther, and is admirably suited to cases in which an a nes i he tie is not used. The thumb being abducted, the knife is made to cut its way between the lir-1 and econd metacarpal bones until the base of the former is reached (Fig. 11".)). The thumb being greatly ab- Fia. 129. ducted, the joint between its metacarpal bone and trapezium is opened and traversed. The knife is then carried downward upon the radial side of the bone, where, by cutting outward to the level of the interdigital web, a radial flap is made. Amputations of the little finger with its metacarpal bone can be made in the same manner, either by the oval or by the flap method. Injuries of the palm of the hand are generally of such a nature that by a little ingenuity on the part of the surgeon part of it can be preserved. "\\ hen in rare cases disarticulation of the last four metacarpal bones becomes necessary, the thumb being left, it may be done as follows: The hand being grasped and held in supine position, a long, narrow blade is passed through the palm from the base of the fifth metacarpal bone to the web of the thumb. By cut- ting outward, a broad semilunar flap is made (Fig. 130). An incision is next made on the back of the hand, beginning at the web of the thumb and carried obliquely upward to the upper third of the second metacarpal bone, whence it is continued transversely over the three last metacarpal bones until it meets the palmar flap at the ul- nar border of the hand. Both flaps are thus re- flected to the carpo- metacarpal joints, and disarticulation is ef- fected from the ulnar side, the hand being forcibly abducted. Amputation at the Wrist. — In amputa- tions at the wrist the surgeon has the choice of the circular and the tegu- mentary flap methods, both of which leave an excel- lent stump. Circular Method. — Retracting the skin of the fore- arm with his left hand, the operator carries the knife in a circular sweep around the hand one inch below the styloid processes. The skin and subcutaneous layers, being liberated by incisions perpendicular to the axis of the limb as far as the styloid processes, should be reflected like a cuff. The hand being then pronated and forcibly flexed, the tendons are divided and the joint opened by an incision over the dorsum from one styloid process to the other. In making this Fig. 130. 2S1 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES incision the convexity of the upper surface of the carpus must be remembered. The lateral ligaments being next severed, the anterior part of the capsule and all the flexor tendons are cut through with one stroke of the knife (Fig. 131). Fig. 131. Anteroposterior Flap. — The operator seizes the lower part of the pronated hand, and after flexing it makes a semilunar incision over the middle of the back of the hand from one styloid process to the other (Fig. 132). After reflection of the flap the joint is opened as in the circular operation, and the operation is completed by cutting a short palmar flap from within outward (Fig. 133). The projection of the pisiform bone often renders this part of the operation embarrassing. Method of Dubreuil. — A very excellent result can be obtained by making a single lateral flap, either from the radial sur- face of the thumb or from the soft parts covering the fifth metacar- pal bone, the former being preferable. As will be seen from Fig. 134, the operation c onsis ts in making a semi- lunar flap with broad base, from the integ- ument which covers the first me tacarpa 1 bone, the point of the flap reaching the base of the first phalanx. A transverse incision around the wrist is then made and disarticulation is completed as in the other operations. Amputation of the Forearm maybe practised by the circular, tegumentary, or musculotegu- mentary flap method. The lower third of the forearm, containing a large number of tendons, is ill suited for the latter method, the circular oper- ation being preferable (Fig. 135). When the in- tegument is greatly infiltrated and the reflection of a cuff is thereby rendered impracticable, tegument- ary flaps can be made, the tendons being divided by a circular incision (Fig. 130). The presence of a large number of synovial sheaths, and the danger of inflam- 282 Fig. 133. mation in them when they are opened should not militate against the value of operations in the lower third of the forearm, since, by operating below the insertion of the pronator radii teres, movements of pronation and supination will be preserved. A number of surgeons prefer the flap operation in all amputations of the forearm, making both flaps by transfixion in fleshy subjects. Under opposite cir- cumstances the anterior flap can be made in this manner, and the posterior by cutting from within outward. When this method is resorted to, the bones must be divided as high up as possible, to overcome their tendency to protrude at the angles of the wound. Muse ulotegu- mentary flaps should be used only in the fleshy part of the forearm. In all amputa- tions in this part the catlin is to be used, in t lie man n er al ready de- scribed. The divided tendons and nerves must be drawn from the wound and cut as short as possible. The arteries requiring ligation are the radial, ulnar, and interosseous. It is particularly essential that the latter should be divided but once, and carefully secured. When secondary hemorrhage occurs after amputation of the forearm, it is almost always the result of faulty ligation of this vessel. Amputation at the Elbow. — The removal of the forearm at its articulation with the humerus is generally acknowl- edged to have been first performed by Ambrose Pare, in 1536, in the case of a soldier who had re- ceived a gunshot wound of the fore- arm, which was fol- lowed by gangrene. The operation did not meet with much favor by surgeons generally, until it w r as again advised and practised in the second quarter of this century by Textor of Wtirzburg, by Dupuytren, and by Liston. With the exception of Chenu's statistics, the results of amputation at the elbow have been very favorable, the death rate not exceeding fourteen per cent. (Agnew). The last-named writer, however, gives a mortality of sixty-five per cent, as that which attended disarticulations of the forearm during the Crimea. On the other hand, of thirty-nine amputations at the elbow, made during the War of the Rebellion, in which Fig. 134. Fig. 135. the result was determined, only three succumbed; the mortality being less than eight per cent. The operations generally resorted to in amputations at the elbow are the circular and musculotegumentary REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation flap methods. When the former is practised, a circu- lar incision should divide the skin and subcutaneous cellular layer of the forearm ui least two inches below the humeral condyles. When a cuff of sufficient length has been reflected, the anterior surface of the joint is made prominent by hyperextension, and divided by a transverse cut with the end of the knife. When the lateral ligaments are next divided, the joint surfaces are sufficiently separated from each other to permit the knife to be passed behind the ranon, where the tendon of the triceps is to he divided. The latter step of the operation is some- times attended with such difficulty that many sur- preserve the olecranon process by sawing the transversely after disarticulation of the radius has been effected. The advantages which are to he nned by it.-- preservation, on account of the in- fluence which the triceps will have over the artificial limb, are more than balanced by the increased dangers of retention of secretion in the wound and i >>is. Excellent results can also be obtained by tegumen- tary flaps. As represented in Fig. 148 (Esmarch), a curved incision is made over the flexor surface of the forearm, beginning and ending about one inch below the condyles. The large semilunar flap thus made is reflected to its base. A second, but shorter convex flap is made posteriorly, which, when reflected, exposes the olecranon. The operation is then com- pleted by disarticulation, as in that by the circular method. The most brilliant operation, and at the same time a very satisfactory one, is that by which a long anterior flap is made by transfixion. The knife, being introduced a little less than an inch below the external con- dyle (for the right arm) of the humerus, is pushed directly across the front of the articulation to a point on the same level on the opposite side. The arm being held in a supine position, a broad, almost rectangular flap, from four to five inches in length, is made by cutting outward. The ends of the wound should then be united by a slightly convex incision carried across the posterior aspect of the joint. Disarticulation is then effected as in the previous operations. When the soft parts of the anterior portion of the forearm cannot be utilized, the integument of the posterior surface can be shaped into an admirable covering for the end of the bone. Ashhurst thus describes the elliptical incision by which this is ac- complished: " The arm being semiflexed, the point of the knife is entered nearly an inch below the internal condyle of the humerus, curved upward over the front of the forearm nearly to the line of the joint, and downward again to a point an inch and a half below the external condyle; the arm being then forcibly flexed, the ellipse is completed on the back of the forearm by a curved incision passing nearly three inches below the tip of the olecranon. The cuff thus marked out is rapidly dissected upward as far as necessary, when the muscles of the front of the forearm are cut about half an inch below, and the ulnar nerve as far above the joint, and disarticulation is effected from the outer side. The wound is closed transversely, forming a small curved cicatrix in front of the bone!" It is probably always advisable, except in eases of disease, to preserve the articular surface of the hu- merus intact, although Sir William Ferguson believed that a section above the condyles leaves a preferable stump, and one more likely- to heal promptly. In all \ %w ~ T~ ~~^— — Fig. 136. amputations at the elbow, the radial, ulnar, and interosseous arteries require ligation. When the in- ci~i. ui through the soft parts anteriorly is made on a higher level than is ordinarily necessary, the brachial may be divided and require ligation. Amputation of the Asm. — This may be perform- ed at any point below the axillary- folds, and all the methods of amputation may he used with advam in different cases, since the choice of methods often permits the operator to save a considerable portion of Fig. 137. the arm. On account of the central position of the humerus, the arm is properly considered the typical position for the double musculotegumentary flap operation by transfixion, and many surgeons prefer this method in this situation. The objection to be urged against it is the unequal retraction of the in- tegument and underlying muscles, the latter gener- ally protruding a varying distance over the cutaneous margins of the wound. Agnew properly advises that. to overcome this unequal retraction, anteroposterior oval skin flaps should be raised of sufficient length to compensate for the difference in muscular and cutane- ous retraction; after these are made, the muscular flaps are formed either by transfixion or by cutting from within outward. The latter plan of operating, although less brilliant than that by transfixion, should always be preferred in amputations of the arm in Fig. 138. very fleshy subjects. In making the flaps, the posterior should always be made first, the anterior, containing the important vessels and nerves, being made last. According to the dimensions of the limb, the flaps should be made from two to three inches in length. In slender subjects, the circular operation answers admirably. In exceptionally thin arms, the integu- ment can be retracted sufficiently to make the opera- tion by a single circular incision. As a rule, however, 283 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES it is best formally to reflect a cuff (Fig. 137), or to make rectangular cutaneous flaps by slitting the cuff on each side. In dividing the muscles by a circular incision, the biceps generally retracts more than the remaining muscles. The wound is often so irregular in consequence that a second division of the muscles becomes necessary (Fig. 138). In cases of injury attended with great destruction of the soft parts on the dorsal aspect of the arm, the Teale method, by rectangular flaps, offers particular advan- tages. The incisions for making the long anterior flap must be made in such a manner that the inner one shall be without the brachial artery, which should be contained in the short posterior flap. In amputations through the middle and lower thirds of the arm, the circulation can be controlled in the ordinary manner by the Esmarch tube or tourni- quet. In amputations higher up, where the tourni- quet would be in the way of the operator, and liable to slip, the main artery can be compressed against the head of the bone by an assistant, or against the first rib above the clavicle. When a tourniquet is used in amputations in the upper part of the arm, it should be so applied that a roller covers the axillary artery in the arm-pit, while the plate of the tourni- quet can be fixed against the acromial process of the scapula. The arteries requiring ligation after ampu- tation of the arm are the brachial, superior or in- ferior profunda, occasionally the anastomotica, and four or five muscular branches. It should be remem- bered, likewise, that in every fifth subject, according to Quain, there is a high division of the brachial into radial and ulnar. In 5,273 cases of amputation of the arm for gunshot injury, 1,246, or 23.6 per cent., terminated fatally. The gravity of amputation of the arm does not increa-e with the extent of the limb removed, am- putations through the lower third presenting a mortality of thirty-five per cent, against nineteen per cent, for amputations in the middle and twenty- two per cent, for those of the upper third. In the statistics of Gorman, derived from civil practice, this remarkable feature in the prognosis of amputations of the arm is even more pronounced, the mortality following amputations in the upper, middle and lower thirds being twenty-three per cent, twenty-one per cent, and forty-four per cent, respectively. Of fourteen amputations of the arm in the Cincinnati Hospital all recovered. Of 157 amputations of the arm collected from the recent statistics of Erdmann. Page, and my own, twenty, or 12. S per cent., died. Fur the comparative mortality after amputations of the arm for injury and for disease the reader is re- ferred to Tables III., IV., and V. Amputation- at the Shoulder. — Although this operation was referred to by ancient writers on medicine, it was not performed as a formal operation till 1710, when the elder Morand performed it with a fatal result in a case of caries. The case was not recorded until some years later, by the younger Morand. The second operation, which was success- 284 ful, was made in 1715 by the elder Le Dran, likewise for caries. That the arm had previously been re- moved at the shoulder in a case of gangrene appears in the Jour, de Med. de M. Dc la Roque, 1686. "The surgeon took a small saw to remove the bone of the arm, but perceiving that it was loose in the joint, he gave it several slight 'jerks', when the bone was readily drawn from the socket." Ravaton, La Faye, Heister, and Bromfield repeated the operation from time to time on the Continent and in England, but it remained for the distinguished Larrey to give it a Fig. 140. — Showing Wyeth's Pins and the Rubber Tubing in Place. A piece of black court plaster indicates the tip of the acromion. (Taken, by permission, from Keen's article on shoul- der amputations, in the Transactions of the American Su: Association for 1S94.) firm footing among surgical procedures. Of 111 amputations made by him at this part, ninety-seven recovered. In all amputations of the shoulder, the circulation in the axillary artery must be controlled. This can be accomplished by the use of the rubber tube of the Esmarch bandage firmly wound around the axilla and shoulder, and held by an assistant or cL toward the neck of the patient (Fig. 139). To prevent the slipping of the strap, which is likely to occur \\ hen the head of the humerus leaves the socket, two long transfixion pins may be used, the one in front of and the other behind the acromion. The anterior pin is introduced through the middle of the anterior axillary fold near the trunk line. It is made to emerge an inch above the shoulder, one inch to the inner side of the acromial tip. The second pin transfixes the posterior axillary fold in the same manner, emerging behind the acromion (Fig. 140). In all amputations of the shoulder the joint should be approached from the outer side, so that the artery shall not be divided until disartic- ulation has been effected. In this manner an assis- tant can, if necessary, pass his thumb into the wound above the knife (Fig. 141) and compress I he vessel before it is cut. Two pairs of pedicle clamp forceps with blades three inches long applied above the line of division of the inner flap, the one from in front and the other from be- hind, will perfectly con- trol the artery while the operation is being completed. Thereby skilled assistance, and even the Esmarch strap, can be dispensed with. The hemorrhage is from the smaller vessels only and is slight. When the axilla is invaded so high that this plan of Fig. 141. REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Amputation hemostasis is impracticable, the axillary shouUl In- tied by dividing the pectoral muscle as suggested by Delpech, or the subclavian should be tied in its third part, as a preliminary step to the amputation. When such precautions as have been described can be taken, it is not necessary to make a preliminary ligation of the artery in the axilla. Amputations at the shoulder joint can be made by the oval or flap method, and likewise by a circular operation with external longi- tudinal incision. Oval Method. — This operation, generally designated rey's operation (as shown in Fig. 139), is per- formed as follows: The patient being placed in a semi recumbent position, with the part to be amputated projecting over the edge of the operating table, the point of the knife is introduced just beneath the point of the acromion process, and carried down over the external surface for a distance of from two and one- half to four inches, according to the dimensions of the part. This incision should divide all the tissues down to the bone. From the center of this incision an oval cut is carried around the arm, passing a little below the axillary folds, but involving only the skin and superficial fascia. The flaps thus outlined are carefully liberated from the bone. The capsule is then freely opened by a transverse cut over the head of the humerus, and the arm is rotated inward and outward to facilitate the diyision of the tendons of the articular muscles; in this part of the operation, the edge of the knife must be kept in close contact with the bone. The operation is completed by dividing the soft parts on the internal surface of the arm on a level with the cutaneous incision already made. "While it is not essential, in this operation, to cany the oval incision completely- around the arm before beginning the dissection of the flaps, it is preferable, since, without it, the lower part of the oval wound is very apt to be ragged and uneven. The wound following this operation is united so as to leave a linear cicatrix parallel to the axis of the body (Fig. 142, from a photograph of one of Ashhurst's patients). Circular Method. — In cases in which the humerus is shattered to such a degree that it cannot easily be used in the manipula- tions necessary for effecting disarticula- tion, the following modification of the circular incision will answer admirably: The arm being ab- ducted, a circular in- cision at the lower border of, or through, the deltoid divides all the soft parts down to the bone. This, if necessary, is divided on the same level, and all the gaping vessels are Iigated. When the amputation of the arm is thus completed, a long incision, dividing all the soft parts, is made from the tip of the acromion over the external surface of the shoulder to the circular wound. The remaining stumd of the humerus is then seized with a strong pair of forceps, and liberated from its muscular attachments and from the joint by short incisions directed well against the bone (Esmarch). Flap Method. — Amputation at the shoulder by the flap method can be made either by transfixion or by cutting from without inward. The latter method, while less brilliant, is preferable in every way. It Fig. 14_\ Fiq. 143. should be performed in the following maimer: In amputation of the left arm the operator begin- his incision at the coracoid process, and carries it down over the anterior surface of the shoulder to the level of the insertion of the deltoid, across which it i~ carried in a wide curve; it is then prolonged upward on the posterior surface of the shoulder to the junction of the acromion with the spine of the scapula 1 1 it:. 143). This broad flap, including a great part of the deltoid, is then raised by rapid strokes of the knife and reflected over the acromion in order that the joint may be exposed. This is made prominent by pushing the head of the humerus upward, and is to be i ipened by a trans- cut upon the latter. The head of the bone is now easily dislocated. The knife is then car- ried behind the hu- merus (as shown in Fig. 141) and down its inner surface to a point one or two inches below the axillary fold, when, by rapidly cutting out- ward, all the soft parts on the inner side are divided. In making this oper- ation by transfixion (Dupuytren's method) the arm must be held at a right angle with the body, while the surgeon grasps and raises the fleshy part of the shoulder with the left hand. The knife is entered one or two inches behind the acromion and pushed directly across the front of the joint, emerging just outside the coracoid process of the scapula. Transfixion being effected, a broad flap is cut from within outward. The further steps of the operation are similar to those above detailed. Both of the operations described leave a wound that, from its position, is more readily drained than that which is left by the oval method. The cica- trix which remains is transverse in direction and curvilinear. A wound closely resembling that left by Larrey's oval operation remains after the formation of postero- external and antero-internal flaps by Lisfranc's method. In practising this method, when the left arm is to be removed, a long and narrow amputating knife is introduced at the margin of the posterior axillary fold. The blade is then pushed along the posterior surface of the humerus until the head of the bone has been cleared, when the counter-puncture can readily be made an inch beneath the clavicle and on the outer side of the coracoid process. A broad postero-external flap must then be shaped by cutting from within outward. The capsule is then opened as in other operations, and an antero-internal flap cut likewise from within outward. In operations on the right side the posterior flap is also made first; the surgeon, standing behind the patient, inserts the point of the knife from above and lets it emerge from the posterior axillary fold. Professor Spence of Edinburgh introduced a method of amputating which is but a modification of the ova] operation, in which the perpendicular incision is made upon the head of the humerus, nearer to its inner than its outer surface. This incision is com- menced just beneath and outside of the coracoid pro- cess and carried through the clavicular fillers of the pectoralis major and deltoid muscles until the hu- meral attachment of the former is reached. From the lower end of this incision the external and internal curvilinear incisions are almost the same as those of 285 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the oval operation as generally practised. The ad- vantages claimed by Professor Spence for this modi- fication are the facility with which the disarticulation can be effected, the avoidance of injury to the main trunk of the posterior circumflex artery, and the better shape of the stump. The prognosis of amputation of the shoulder has been very greatly improved. For example, from Estes's statistics from the South Bethlehem, Pa., Hospital, of twenty-two amputations at the shoulder joint done during twenty years only one died. This is in contrast to the amputations done on the battle field or in military hospitals. Of seven cases re- ported by Col. Stevenson, two or twenty-eight per cent. died. Most of these cases were septic when operated on. IxTEKSCAPULO-THORACTC AMPUTATION. In the first edition of this work fourteen cases of avulsion of the entire upper extremity were referred to, which ended favorably. In Ashhurst's "Surgery," seven- teen cases are recorded of such avulsion which ended favorably. Here also are recorded eighty-nine cases, in which the entire upper extremity including the Fig. 144. — Interscapulo-Thoracic Amputation. (After Treves.) scapula and part of the clavicle was removed by operation, with sixty-seven recoveries and twenty- two deaths. Bergmann has put on record fourteen amputations of the entire upper extremity, with only one death. Favorable cases have likewise been recorded by Chavasse, Ochsner, Keen, Doll, and Heddaens. Barling" collected nineteen cases operated on within five years without a death. Jeanbrau Riche collected 188 observations from sixty surgeons. The mortality was 11.1 per cent. But, while the operations performed before 1S87 or when the tech- nique was imperfectly developed, showed a mortality of 29. 16 per cent. ; those performed after 1887 showed one of only 7.84 per cent. If cases in which intervention was contraindicated are left out, the figures could be reduced to 5.2 per cent. Of 125 cases in which the nature of the new growth had been determined by a microscopic examination, recovery followed in 105. Of the twenty others, ten died from operation, and reports about another ten could not be obtained (Rodman). The operation is indicated in cases of severe crush of the upper extremity when exarticula- tion at the shoulder would not suffice, and in neo- plasms of the upper extremity when it is essential to get as far as possible from the disease. The first opera- tion was done by Gumming, in 1808, for gunshot injury; the second, in 1830, by Gaetaui for a severe trauma from an explosion. In 1887 Paul Berger tabulated all of the cases recorded up to that time, and submitted the most comprehensive monograph upon tin- subject. As in amputations at the shoulder joint, the control of hemorrhage is the essential point of the operation. It is now the consensus of opinion that the first step of the operation should be the resection of the middle third of the clavicle as a preliminary step to the tying of the subclavian artery and vein. It is essential to tie the latter as well as the artery, in order to prevent the ingress of air. According to the publication by Nasse of Bergmann's cases, the Berlin surgeon begins his operation with the typical ligation of the subclavian artery to the outer side of the ante- rior scalenus muscle. This is followed by division of the clavicle. The arm is then elevated and the sub- clavian vein tied. The brachial plexus is at once divided. Ochsner has called attention to the fact that this plexus ought to be divided with a sharp knife rather than with scissors, since the shock is thereby greatly lessened. Le Conte has wisely suggested the complete excision of the clavicle in place of resection of its outer portion. In malignant disease it is preferable, and when once accomplished simplifies the control of the vessels. The cutaneous incision must vary somewhat according to the degree to which the soft parts about the shoulder are in- volved. Bergmann makes an anterior incision, through the skin only, from the incision made for the division of the clavicle straight through the axilla to the lower angle of the scapula. The posterior in- cision is made over the dorsal aspect of the scapula from the resection line of the clavicle to the end of the anterior incision. The illustration will indicate the lines of incisions recommended by Treves. That for the antero-inferior flap extends outward from the incision made for the division of the clavicle to the outer and lower border of the axilla, which it crosses directly from before backward, whence it passes downward to the lower tip of the scapula posteriorly. The posterior incision extends across the upper sur- face of the shoulder, from which it inclines over the scapula to its lower angle, as seen in the illustration. After the lifting of the cutaneous flaps, the muscles are divided and the small vessels tied as they are encountered. In one of Kern's cases, owing to the involvement of the parts about the acromion, an oval incision was made beginning three inches above the acromion, each limb passing in front of and behind the shoulder respectively, and meeting in front of the inferior angle of the scapula. In the cases of recovery, the wounds heal within the course of ten days or two weeks. In operations for malignant disease, the prog- nosis is far more favorable when it is done for myeloid sarcoma than for periosteal sarcoma. The prognosis is more favorable in those cases in which the soft parts about the shoulder are not involved. Thus in all the cases of Heddaens recurrence rapidly took place. Amputation of the Toes. — It is occasionally necessary to remove the toes in consequence of accident, disease, or deformity. While in cases of accident, it may occasionally be well to save a part of one of the smaller phalanges, it is generally best that the amputation be made at the metatarso-phalangeal joint. In amputations of the phalanges, a flap operation, like that for the fingers, must be made, care being taken, as in all amputations of the foot, that the cicatrix is placed on the dorsal aspect of the stump. In amputations of an entire toe, the in- cision should be commenced on the dorsal surface of the metatarsal bone, a little above the joint, but considerably above the web, and carried directly down an inch or more. It is then carried obliquely around the web on each side, in such a manner as to preserve as much of the soft parts as possible. This preservation of tissue is necessary for a sufficient covering for the large head of the metatarsal bone. When the operation is performed in this manner, the cicatrix is linear and entirely removed from pressure. No part of the metatarsal bone should be removed, lest the strength of the foot be deteriorated. Dis- articulation of the great toe may be effected by the oval method just described, or by the formation of 286 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation an internal flap. In 1 ho latter case, an incision is begun on the outer side of the extensor tendon, just below the joint, and carried longitudinally to the head ,,i the first phalanx, from its lower end an incision j- carried transversely around the inner side, to the flexor tendon, along the outer side of which it is continued backward to the plantar fold, whence it is again given a transverse direction around the outer siTle of the toe until it meets the first incision near its center (Stimson). The rectangular flap thus marked out. is dissected up, the tendons are divided, and disarticulation is effected. Although it is s times ommended, the head of the lirst. metatarsal bone should never be re ved unless it is implicated in the lesion, since it tonus one of t ho most important points of support in the foot. Amputation of all the toes at the metatarso- phalangeal joints may be made by carrying a curved incision along the groove between the base of the toes and sole of the foot from one margin of the latter to the other. The toes being forcibly flexed, a similar incision is made along the dorsum, which joins the ends of the plantar wound. The semilunar flaps thus formed are dissected back as far as the meta- tarso-phalangeal joints, when disarticulation of the individual toes can be made. It certainly _ cannot be often that a formal operation of this nature is called into requisition. Amputation through the Metatarsus. — In consequence of injury or disease it not unfrequently becomes necessary to remove a part or all of the metatarsal bones. In amputations through individ- ual bones of the metatarsus, conservatism must be particularly insisted upon, since, except in that of the great toe, the complete removal of a metatarsal Bone cannot be accomplished without opening the large synovial sac which separates it from the first row of the tarsus. For amputations through the second, third, and fourth metatarsal bones, the longitudinal incision necessary for disarticulation at the metatarso-phalangeal joint must be carried upward for a distance varying according to the extent of bone to be removed. A short transverse incision is then made to facilitate the separation of the soft parts and the use of either chain-saw or bone- cutting forceps. When the bone has been divided. its distal end is drawn from the wound with a pair of stout forceps, and the operation is completed by severing the soft parts on the plantar surface of the foot with short strokes of the scalpel. The removal of the first and fifth metatarsal bones can be accomplished by the oval method or by internal and external flaps respectively. The oval method, where it is practi- cable, is doubtless preferable, since it yields a smaller wound and a cicatrix protected from pressure. The incisions for the oval amputations of the great toe with its metatarsal bone are well shown in Fig. 145. ( in account of the great width of the base of the latter bone, a short transverse incision facilitates the libera- tion of the flaps. In disarticulations of the fifth metatarsal bone the oblique line of its articulation with the cuboid bone should be borne in mind. When the first or fifth metatarsal bone is amputated in its continuity, the section should be made obliquely to avoid undue prominence of the stump. Amputation in the continuity of all the metatarsal bones is not very infrequently called for, in consequence Of injury or gangrene following frost-bile. \\ hen it can be resorted to, it is preferable to amputation through ihe tarsometatarsal articulation. The operation is commenced with a curved incision carried along the anterior furrow of the Bole of the foot , from bonier to border, and the semilunar flap thus outlined is reflected to the line where section of the bones is to be made. A smaller semi- lunar flap is then shaped from the dorsal surface of the foot. The interosseous soft parts are then divided transversely with a narrow knife, and retracted by means of narrow strips of linen, when the bones are sufficiently exposed for the application of the saw (Fig. 140). The appearance of the wound resulting from t his oper- ation is well shown in Fig. 1 IT. In this age of conservatism Fia. 146. in surgery, in which "the least sacrifice of parts" is the lead- ing tenet of surgical creed and practice, every half-inch of the foot that can be saved to the economy is properly considered of incalculable value. It is for this reason that, whereas before the times of Hey, Chopart, and Lisfranc, amputations of the foot above the ankle were made comparatively often, they have of late been largely replaced by partial amputations through the differ- ent articulations which it con- tains. The partial amputations which will be considered are the tarsometatarsal, the mediotarsal, the subastragaloid, and their modifications. Tarsometatarsal Amputa- tion. — A glance at Fig. 149 shows the difficulty which the surgeon must contend with in this amputation of the foot. It is the firm impaction of the base of the second metatarsal bone between the internal and ex- Fig. 147. ternal cuneiform bones. In 1797, Mr. Hey, of Leeds, overcame this difficulty by disarticulating the outer metatarsal bones, and divid- ing the prominent internal cuneiform with a saw. .Surgeons after him have generally adopted the plan of separating the outer three and the internal metatarsal Fig. 148. bones at their articulations, and dividing the base of the second metatarsal below its articulation with the middle cuneiform. When disarticulation of all the metatarsal bones is effected the operation is known as Lisfranc's (1815). 2S7 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Lisfranc's amputation of the foot is made as follows: The joint between the cuboid and prominent base of the fifth metatarsal bone having been marked on the outer side of the foot, and that between the first metatarsal and internal cuneiform (about one inch and a half below the tuberosity of the scaphoid) on the inner side, a large semilunar incision is made between them on the sole of the foot, the convexity of which should pass over the heads of the metatarsal bones. The plantar flap thus out- lined may then be dissected up to its base. The foot being then for- cibly extended, a slightly convex dorsal incision is carried between the ends of the plantar flap (Fig. 149). The flaps being retracted and the foot forcibly extended, the operator opens the joint from the outer or inner side, according to whether the right or the left foot be the seat of the operation (Fig. 150). The articulation of the second metatarsal bone, which is less than half an inch above the general level of the joints, must then be opened by a transverse cut, the lateral attachments of the bone Fig. 149. Fig. 150. to the cuneiform being severed with the point of the knife by longitudinal incision (Fig. 148). When all the joints are widely opened by this process, the re- maining ligaments at the side and sole of the foot, and the soft parts still undivided, are severed. As the operation is gen- erally performed, the plantar flap is merely outlined by an incision through the skin in the first step of the operation, the flap being cut from within outward after dis- articulation has been effected. The vessels usually requiring liga- tion are the dorsal artery of the great toe, the metatarsal branches, and the plantar arteries. When the parts are brought together by suture, the stump should be placed in a posterior splint, to overcome the contraction of the powerful muscles of the calf of the leg. In Hey's amputation, the external incisions are identical with those necessary for the Lis- franc operation. The cicatrix resulting from either of these procedures is far re- moved from pressure, and the stump, on account of it- length, is one admirably fitted for use. 288 Fig. 151. Mediotausal Amputation. — Although Garengeot and Heister mentioned the practicability of ampu- tation between the rows of the tarsal bones, the operation was first performed by "Du Vivier of Rochefort in 1781. In 1701 Chopart repeated the operation a number of times. anc ] published his Fig. 15U. Fig. 152. experience with it. It has since been known as " Chopart 's amputation," and the joint between the rows of the tarsus is not infrequently designated by his name. Although it was opposed by Larrey, who preferred to amputate in the lower part of the leg, the operation was popularized by Roux and Walt her on the Continent, and by Mr. James of Exeter and by Syme, in Great Britain. The articulation between the scaphoid and the head of the astragalus, and that between the cuboid and os calcis are respec- tively placed one-half inch above the tuberosity of the scaphoid on the inner border, and one inch or more above the prominence of the fifth metatarsal bone upon the outer border of the foot. These two points being fixed, a curved incision, extending to within an inch or less of the heads of the metatarsal bones, is carried across the sole of the foot, and connects them. The foot being then forci- bly extended, a curvilinear inci- sion, with convexity below, is carried between the same points across the dorsal surface. The small dorsal cutaneous flap thus outlined is retracted, and by one stroke of the knife the tendons are divided and the joint widely opened. The point of the knife then divides the la.e.al and plantar ligaments, which are put on the si ret eh by forcible extension until the articular surfaces of the scaphoid and cuboid bones are completely liberated. By in- serting the knife behind these bones, the plantar flap is completed by cutting from within outward (Fig. 152). The vessels requiring ligation are tin- dorsal and two plantar arteries, and occasionally a few muscular twigs. The appearance of the stump after the completion of Chopart 's amputation is well shown in Fig. 153, from Esmarch. The only difficulty at times encountered in this operation is in the opening of the joint in front of instead of behind tlie scaphoid bone. The error is readily recognized through the presence of three Fig. 154. REFERENCE HANDBOOK <>F Till'. MEDICAL SCIENCES Amputation articular facets cm the anterior surface of the scaphoid DOne> and ran easily be corrected if it be desired, or :!,, operation may be completed by dividing the cu boia bone with a saw on a line with the anterior , ,. of the scaphoid. In this ma unci' the operator would be practising Forbes' modifi- cation of the mediotarsal amputa- t ion, a mm lificai inn also menl ioned by Mr. Hancock and Professor Agnew. After Chopart's amputation, the gastrocnemius and soleus having exclusive control of the stump, there is a marked tendency toward iis hyperextension. This may as- sume such a decree (lull I lie cical rix itself will he pressed upon in loco- motion. This objection to the operation is best overcome by bandaging the leg from above down- ward, and keeping (he limb flexed. In extreme cases the difficulty is easily remedied by division of the tendo Achillis, and forced flexion of the stump. SuBAsruAOAi.oiD Amputation. — Although, according to Velpeau, this operation was I by De Lignerolles and by Textor, it was first given prominence by Malgaigne, in 1846. In this amputation all the bones of the foot, except the astragalus, are removed. The operation is com- menced by an incision, which, beginning behind and i m me tl iat ely abov ■ the great tuberosity of the os calcis, at once divides the tendo Achillis. The incision is then carried in a wide curve on the outer sur- of the os below the external malle- olus (Fig. 154, Malgaigne). Thence it is continued over the middle of l lie cuboid and anterior margin of the scaphoid, across the dorsum of the foot (Fig. 155), and over its inter- nal border to the center of the sole (Figs. 150 and 157). From this point the incision is turned at a right angle and continued directly back till it meets the beginning of the incision at the inner border of the tendo Achillis (Es- march). The short internal and long internoplantar flaps thus formed arc dissected up until the lateral surfaces of the os calcis are exposed, when dis- articulation of the anterior part of the foot is effected in the mediotarsal joint. The anterior end of the os calcis being then seized with a lion- jawed forceps, and rotated from side to side, the operation is completed by dividing the external lateral and interosseous ligaments. The appear- ance of the stump after this opera! inn is shown in Fig. 158 (Esmareh). The marked irregularities of the inferior surface of the astragalus do not inter- fere with its usefulness in locomotion. In a case of gangrene in a deformed limb, Linhart performed the sub- astragaloid amputation, and was enabled two years later to examine the stump. The astragalus, which had maintained a perpendicular position before, and even at the time of amputation, had been forced into its normal horizontal position by the act of walking. Vol. I.— 19 Fia. 156. Fig. 157. Fig. 158. A number of modifications of the subastragaloid amputations, both in the direction of the inci ions and in the preservation of parts of 'in- c, calcis, have been devised. In the operation of Mr. Hancock, a. large plantar flap i.-; reflected a fai back a i he i uber- osities of the calcaneum, and a short dorsal flap is formed by a transverse incision across the fool on a le\ el u ii h i he anterior margin of the astragalus. By (he use of a saw, the plantar flap being ret racted, a per- pendicular section of the os calo is then made in front of the tuberosities. Disarticulation of the foot, with the anterior port ion of tin rj calci .in (lie mediotarsal joint is next effected, and the operation completed by making a transverse section of i he astragalus. When the flaps are approximated the divided surfaces of the latter bone and os calcis are broughl into appo- sition. The operation of Mr. Han- cock, although as ingenious as that of 1'irogolf, is much more difficult of ex- ecution, and lime will probably show that the results obtained from it are far less valuable. In Tripier's opera- tion the incision is made in the form of an oval, the apex of which is on the outer side of the foot, just beneath the external malleolus, while the Miles pass forward and inward over the back and sole of the foot, and meet at its inner border. After disarticulation in the mediotarsal joint, a transverse section of the os calcis completes the operation. Partial amputations of the foot, at least in civil practice, are not attended with great mortality. Of 152 cases of Chopart's amputation examined by Hancock, only eleven terminated fatally, seven per cent.; the fatality following this operation in France has been much greater, fourteen out of thirty-eight cases recorded by Larger (3G.8 per cent.) having died (Ashhurst). Of twenty-two cases of the subastrag- aloid amputation, twenty recovered. Of 123 partial amputations of the foot, made during the Civil War, in which the result was determined, eighteen were unsuccessful, the mortality being fifteen per cent. Of these partial amputations there were eighty-three of the mediotarsals, with eleven deaths; twenty-three Lisfranc operations with one death, and seventeen Hey's amputations with six deaths. Of sixteen amputations of the foot at the Cincinnati Hospital, one died. The mortality accor- ding to Erdmann's tables is 7.8 per cent. According to Page's tables the mortality is 3.8 per cent, for traumatic and 1.6 per cent, for pathological cases. In making a partial amputation, it must be remem- bered that the value of the stump for locomotion is proportionate to the length of foot maintained. Man- ufacturers of arti- ficial limbs main- tain that conserva- tism is out of place here, ami that am- putation several inches above the Fig. 159. ankle should be given preference over partial amputations m front of or at the ankle. Amputation at the Ankle. — Historically associ- ated with this operation is the name of Synie of Edinburgh who, in 1842, devised and practised a method by which a shapely and useful stump could be obtained after removal of the entire foot. Dis- articulation at the ankle had been performed during the last and early part of this century. It was pcr- 289 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES formed by S6dillier, Rossi, and Baudens, and recom- mended by Brasdor and Sabaticr. But the circular ration of the latter and the dorsal flap method of Baudens yielded alike unsatisfactory results, and the operation was, therefore, discarded for amputation in the lower part of the leg. Lateral flaps taken from below the malleoli, as suggested by Velpeau, also failed to form a sufficient cushion for the end of the tibia. This great desideratum in amputation at the ankle is squarely met by the operation of Syme, since its principal feature is the retention of the integ- ument of the heel, which is accustomed to pressure, to form the end of the stump. The operation is made in the following manner: The foot being held at a right angle to the body, the malleoli are fixed by the thumb and fingers of the left hand, the heel resting between them. A perpendicular incision touching the bone is then made across the sole of the foot from the tip of one malleolus to that of the other, the incision on the inner side, however, ending at least one-half inch below the malleolus (Fig. 159). The posterior lip of the wound is then seized with the left hand, and the soft parts covering the calcaneum are separated from it by short strokes of the knife, which must be kept close against the bone to prevent perforation of the integument and damage to tin- plantar vessels. When, by this process of dissection, the tuberosities of the os calcis nave been fairly ex- posed, a transverse incision joining the two extrem- ities of the first is carried across the instep (Fig. 159). The ankle-joint being thus opened from in front, the knife is carried down on each side of the astragalus until the lateral ligaments are divided, when complete disarticulation is effected. By forcibly depressing the foot the tendo Achillis should then be divided from before backward, when by a few strokes of the knife the foot can be removed (Fig. 160, Esmarch). Fig. 160. Lastly, the knife is drawn around the extremities of the tibia and fibula, so as to expose them sufficiently for being grasped in the hand and removed by the saw. "After the vessels have been tied and before the climes (.1 the wound are stitched together an open- ing should be made through the posterior part of the flap where it is thinnest, to afford a dependent drain for the matter." The appearance of the wound after Syme's amputa- tion is well shown in Fig. 161. It will be seen thai the heel flap presents the form of a cup, which must be flattened by pressure against the bones of the leg. While there is danger, therefore, of making the flap too short, there is likewise a danger in making it too long, since a pouch would be formed for the retention of inflammatory products. Moschcowitz 12 modified the Syme operation by making osteoplastic flaps, whereby no exposed bone is left in the wound. From the external malleolus he chisels a triangular wedge and from the internal malleolus a rectangular wedge. When the exposed bone surfaces are brought in contact only bone covered by periosteum and the cartilaginous lower end of the tibia come in contact with the wound. The favorable results which follow Syme's amputa- tion in civil practice are shown by the statistics of Hancock and Spence, who, among 316 operations, found only 25 deaths (7 per cent.). In military practice the results are far less favor- able. Of 159 amputations made at the ankle during the Civil War, and in which the result was determined, 40 terminated fatally (25.1 per cent.). Pirogoff's Amputation. — On the principle that by preserving the posterior por- tion of the calcaneum the natural length of the limb could almost be preserved, Pirogoff, during the Crimean war, devised the osteoplastic operation that bears his name. It differs from the operation of Syme in preserving a por- tion of the os calcis, in the expectation that it will unite firmly to the divided end of the tibia. The incisions for this amputation are identical with those made in Syme's operation. After opening the joint from in front, the foot is depressed until the posterior ex- tremity of the astragalus is exposed, when a saw is introduced behind this, and the os calcis divided ex- actly on a level with the incision in the sole of the foot (Figs. 162 and 163, Esmarch). Both malleoli and a thin section of the tibia are removed, as i,i Syme's operation. It is generally advisable to divide the tendo Achillis and at the same time to perforate the skin for the passage of a drainage tube. The Fig. 161. appearance of the stump after a successful Pirogoff amputation is well shown in Fig. 164, taken from a man who died three years after the operation was made by Linhart. A number of modifications of Pirogoff's amputa- tion have been devised. Ferguson and Agnew have wedged the end of the os calcis into the interval between the malleoli, and have obtained good re- sults. Different methods of dividing the bone have been devised by Sedillot, Gunther, Le Fort, and Bruns, to remove the pressure from the thin part of 290 REFERENCE HANDBOOK OF TIIK MKDH'AI. SCll'.xri'.S Amputation ili,' integument on the back of the heel, which mil I bear it after the Pirogoff amputation, and to keep the retained part of the os calcis in its natural position. Sgdillot and i Silnthei . therefore, ad- vised t liat an oblique sect en 1 1 abi i\ e dowm* ard and forw ard I oi the calcaneum, tii>ia. and fibula be made. Le Fort ( Fig. 163 i advised a Iran- verse ection of t he bone, by imp obtains a very broad base. Bruns has modified t he operation of Le Fort by sawing the os calcis in such a man- ner as to make the upper sur- face of the retained part concave, the concavity thus formed receiving the convex section of the tibia and fibula. A further modification of Syme's amputation is that of Guyon. It is an amputation above the mal- leoli. The operation is begun with an elliptical in- Fig. 163. Fig. 164. cision beginning one inch above the lower edge of the tibia in front, which, passing obliquely in front of the ankle, crosses the heel below the attachment of the tendo Achillis. The posterior portion of the flap is dissected from the heel and the tendon divided close to its insertion. The anterior extensor tendons are divided transversely as high as possible. After the malleoli are exposed the fibula and the tibia are divided just above them. The heel end of the flap is then brought forward to cover them. The suture line is safe from pressure. A comparison of the merits of Syme's amputation and its osteoplastic modification shows that a cure follows more rapidly after the latter than after the former, although the mortality of Pirogoff's amputation against 21.4 147 cases of in military practice is Fig. 165. per cent. per cent, following that of Syme. Of Pirogoff's amputation collected bj li "hl\ foui ' ' ived fatal, and Volk- mann has performed the operation thirty-fo without a death. Considering the number of reampu tations after S\ me' and Pirogofi operation l ter would seem to 1 ii ul. < >f eighty- t In- -i-es cif Syme's amputation, i v enty, or twenty- four per cent., submit ted to reamputation ; ol fo nine Pirogoff's operation . eight, or L6.3 per rent., were subjected to reamputat ion. In cases of caries involving all the bone- of the tar- sus, preference should be given to the Syme opera- tion, since disease is not unlikely to develop in the retained segment of the calcaneum. In traumatic the greater ease with which it is made and the length of limb which follows it should incline the operator to choose the operation of Pirogoff. That necrosis often follows the latter operation is emphatic- ally denied by its originator, who had never witne ''I it in over sixty cases in which he had performed it. Amputation op the Leg. — An amputation may be performed in any part of the leg. according to the nature and seat of disease or injury. When the sur- geon can select the seat of operation, the amputation should be made two or three inches above the mal- leoli, on account of the greater safety of the opera- tion in this locality and the greater power to be exerted over an artificial limb. In all amputations of the leg, the fibula should be divided from half an inch to an inch above the saw line of the tibia, to prevent pressure against the outer wound margin. The operations which have hitherto been most fre- quently performed in amputations above the malleoli are the circular and that by lateral flaps. Unhappily, the anatomical construction of the part is such that after these operations the cicatrices are central and not infrequently adherent, and therefore unable to bear pressure. In this situation M. Guyon practises the elliptical method. According to Stimson, this operation promises well. " The incision is made in the form of an ellipse, whose lower end crosses the heel below the insertion of the tendo Achillis, and whose upper end is about an inch above the anterior articular edge of the tibia. Beginning at the lower end and dividing the tendo Achillis at its insertion, and hugging the bone all the way, the operator dis- sects up the flap posteriorly as high as the upper end of the ellipse. The anterior muscles are then divided by transfixion, the bones sawn through, and the pos- terior tibial nerve resected. In this operation the sheath of the tendo Achillis is not opened, and the tendon itself serves afterward as a covering for the ends of the bones." Fig. 166. In amputations in the lower third of the leg in fleshy subjects, a long anterior flap containing the interosseous muscles may sometimes be used with advantage (Bell). The rectangular operation of Teale may likewise be practised in this region, the long anterior flap being made from the soft part of its anterior aspect (Fig. 134 see above, Methods of Amputation). By this method the cicatrix, being placed posteriorly, is out of the way of pressure. 291 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES In the middle and upper thirds of the leg very many operators amputate by means of anteropus- terior flaps, after the following manner (for the left limb): The point of the knife being entered at the posterior edge of the tibia, an incision is carried down- ward along this for a distance of an inch and a half or two inches; then by a wide curve across the ante- rior surface of the leg it is continued to the posterior border of the fibula, up which it is carried until the level of its commencement on the opposite side is reached. The broad flap thus outlined is rapidly operation the knife is entered a little external to the crest of the tibia, and while the soft parts are drawn to the outer side with the left hand, it is made to graze the surface of the fibula and to perforate the posterior surface of the limb as far to the inner side of the fibula as possible. By cutting downward close to the bones a broad rounded flap three to four inches long is formed. The extremities of this flap are then united by a slightly convex incision across the anterointernal aspect of the limb. '[ he remaining soft parts being then divided by circular in- cision, the operation is com- pleted in the ordinary way. In Langenbeck's operation, the internal incision is semi- circular, and the external flap being cut from without pre- Fio. 167. Fig. 16S. Fig. 169. Fig. 170. Figs. 167 to 170. — Osteoplastic Amputation, after the -Method of Bier. (Langenbeck's Arch. f. Chir., vol. xlvi.) dissected up, the interosseous muscles being care- fully severed from the underlying membrane. The posterior flap is then made by transfixion and cutting from within outward, and should be about three inches long (Fig. 166, Erichsen). The flaps being held out of the way, the catlin is to be used for com- pleting the division of the interosseous soft parts, care being taken that the arteries be divided trans- versely and only once. After division of the bones with a saw, the sharp anterior edge of the tibia should be removed with the saw or bone-cutting forceps. For the upper portions of the leg the long poste- rior rectangular flap amputation advised b3 r Henry Lee gives an excellent result. Tin' incisions, similar to those of the Teale operation, involve only the skin, the long flap being made from the posterior, the short one from the anterior surface of the limb. With the long posterior flap only the superficial muscles of the calf are reflected, the remaining soft parts being divided by a circular incision. A good covering is likewise obtained in this region by an external flap, made either by transfixion (Sedillot), or by cutting from without inward (Langenbeek). In the former 292 sents a smoother surface and a more perfect outline. The arteries requiring ligation after amputation of the leg are the tibials, peroneal, and a varying number of muscular-branches. ,S iili/n rinst, nl Amputation. — When amputations of the leg are unsatisfactory, it is chiefly because of two things, namely, gangrene of the flaps, and the ten- dency of the stump to become conical, or. at any rate, to be unable to bear pressure. It is for this reason that Bruns devised his subperiosteal amputation, of which he reported seventeen cases in 1S93. Accord- ing to a report by Hahn 13 this operation was per- formed in eighty-four cases without a death. In only three cases was there gangrene of the flaps and in only two cases was a second amputation necessary. The operation is performed as follows: The skin being well retracted by an assistant, a circular incision involving all the soft parts is carried down to the bone. The two perpendicular incisions, from two to three inches in length, are then made, one along the inner border of the tibia, the other between the mus- cles over the fibula. Both incisions are carried to the bone through the periosteum. Through these inci- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation aiona all the sofl parts, including the periosteum, are raised from the bone. After the soft pari- are well retracted the bones arc divided in the usual way. \i ;i . r the amputation has been completed, there remain an anterior and a posterior Hap of periosteum, muscles, and skin. The mu cles are united sepa- rated by buried suture. When the amputation is in the upper portion of the leg, tne circular incision through the skin is made as a higher level than thai through the muscles. Osteoplastic AmptUations of the Leg.— la 1892, Bier' firs! described a method of securing a weight- bearing stump, which, in patients who are unable to purchase an artificial limb, secures for them a stump which will bear the body weight. The operation con- sists of the usual circular amputation. Thereupon follows, through an oval window cut into the sofl parts, a cuneiform excision of part of the Sbula. a the resection surfaces of the tibia are brought apposition a kind of artificial foot project - ante- riorly. The posterior surface of the tibia covered by the -oft parts of the calf bear pressure. Bier has ned iii many cases with uniformly good results. Some German surgeons think that this should l>e the normal procedure. A number of minor modifi- cations of the original method have been made. When there is any possibility that the patient can scrim- an artificial limb, the operation has nothing to commend it. Figures 167 to 170 will illustrate the method of amputation and the result. Since good results follow all the different methods of operation in the middle and upper portions of the leg, the surgeon should be guided in his choice solely by the desire to sacrifice as little of the limb as pos- sible. An exception should probably be made in the upper portion of the upper third, where it is better to amputate at the knee than to save only the por- tion of the tibia above its tubercle. The mortality following amputation of the leg, as ha- already been seen, is largely determined by the conditions necessitating it. According to Chadwick, the mortality- of pathological amputations is sixteen per cent.; that of amputations for trauma nearly thirty-seven per cent. The general mortality of the operation at Guy's Hospital for a period of thirty years was thirty-five per cent.; that for traumatic amputations being fifty-five per cent., against fifteen per cent, following those for disease. Volkmann who employs a long anterior and short posterior flap per- formed the operation in fifty-four cases with only four deaths (seven per cent.), of which there were fourteen traumatic cases with only two deaths (fourteen per cent.). Of forty-six amputations in the lei; made by Brums, seven succumbed (sixteen per lent.). The fatality following amputations of the leg in military' practice is well shown by the stat is- le- of Otis. Of 5,314 amputations in which the result was determined, 1,753 terminated fatally, the mortality being 32.9 per cent. From statistics ob- tained during the late War of the Rebellion, it appears that amputation of the leg is attended with least danger when performed in the middle third". The fatality of operations in the upper third was twenty- en per cent., in the middle third, 20.6 per cent.. and in the lower third, 27.6 per cent. The mortality of amputations of the leg has been greatly reduced. Of eighty-one amputation- of the leg five, or 6.2 per cent., died. In the New York hospitals the mor- tality is twelve per cent. In the Newcastle-on-Tyne Infirmary it is nearly seven per cent. Amputation at the Knee. — According to Sab- atier, this operation was first performed by Fabricius Hildanus in 1581, in a case of gunshot injury. Al- though advocated by Guillemeau (1612) in prefer- ence to higher amputation, there is no record of a repetition of the operation until 1764. when it was successfully performed by Hoin of Dijon for trau- matic gangrene. Brasdo'r and J. L. Petit advised the operation, the latter having twice witnessed it. In L830, Velpeau attempted with success firmi- to establish the operation by citing a number of sua iHi cases. The operation was first performed in thi country by Nathan Smith, of New Haven, in 1824, since which time it has gradually grown in popularity. Fergusson and Legouesl for a long ii [uestioned the advisability of the operation, preferring amputa- tion in the lower portion of ilc thigh. Tne rea o which prevailed to give this operation recognition are the greater length of the slump and it>. ability to bear pressure, tin- smaller probability of pyemia, lie- medullary canal remaining unopened, ami, most important of all, the smaller mortality which follows thi- operation, at least in civil practice, as compared with amputations of the thigh. Fig. 171. Amputation at the knee may be practised by either the circular, the flap, or the oval method. In all methods of amputation it is best, if possible, to pre- serve the semilunar cartilages. Thereby the fascial attachments are maintained intact and the tendency to retraction of the flaps is greatly reduced. The circular operation recommended by Velpeau, San- son, and Malgaigne, made by an incision two or three inches below the patella and the reflection of a cuff, is difficult of execution, and should be resorted to only when an insufficiency of tissue prevents the adop- tion of one of the other methods. The oval method has been practised by Baudens and Sedillot, the for- mer preferring the integument from the anterior portion of the leg, the latter that from the posterior portion, as a covering for the end of the femur. The operation of Baudens is performed as follows: An oval incision is carried around the leg, crossing its anterior surface five finger-breadths below the end Fig. 172. of the patella, and its posterior surface three finger- breadths higher than in front. The anterior and lateral portions of the oval are then reflected until the ligamentum patellae is fairly exposed. This is then divided transversely, the capsule is fairly opened, and the lateral and crucial ligaments are divided. In this as in all amputations of the knee, the latter structures should be divided with the point of the knife, and 293 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES $m^'m Fig. 173. from behind forward, to prevent injury of the pop- liteal vessels. When disarticulation has been effected, the soft parts on the posterior aspect of the limb are divided with one sweep of the knife. This opera- tion is, doubtless, preferable to Sedillot's method, according to which the lower part of the oval is placed behind. In amputating at the knee, a long flap may be taken from the anterior or posterior surface of the leg. The latter method, that of Hoin (Fig. 171), can be most readily exe- cuted, but is objectionable on account of the excess of muscular tissue in the flap, and the difficulty of establishing thorough drainage. Lateral flaps have been advised by Rossi and Stephen Smith. The operation which is generally performed, how- ever, is that by one long anterior and one short posterior flap. It is readily performed, and leaves a wound that is easily drained, and a stump in which the cica- trix is protected from pressure. Operation. — The leg being raised, a semilunar flap, three to four inches long, is outlined from the calf, the incision beginning a little below the middle of the lateral border of the condyles. This flap is dissected up as far as its base. The leg being then flexed an anterior flap four to five inches long is outlined on the anterior surface of the leg from the ends of the posterior incision (Fig. 172, Esmarch). The anterior flap is then raised from its attachments until the liga- mentum patellae is en- countered and trans- versely divided. The cap- sule is then extensively incised laterally and the anterior flap including the patella, reflected (Fig. 173). Disarticulation and division of the soft parts on the posterior aspect of the limb are then effected in the manner already de- scribed. This operation is preferable to forming the posterior flap without the guidance of a cutaneous incision. The vessels re- quiring ligation are the popliteal artery and vein, which should be carefully separated and tied indi- vidually. A number of smaller arteries, sural and muscular, will also require ligation in the posterior portion of the wound. A number of operators f Billroth among them) ad- vise the removal of the patella, lest inflammatory products accumulate in the pouch above it. This prpcedgire is generally held to be superfluous, since tin' upper part of the wound can readily be drained without it, and the removal of the patella endangers 294 the vitality of the long flap. It is always advisable, to insure drainage, to divide the lateral attachments of the synovial membrane to the femoral condyles, by which means the retention of inflammatory prod- ucts in the pouch alluded to can be avoided. In 1870 Stephen Smith 15 described an amputation by "lateral hooded flap." It leaves an admirable stump, the cicatrix being placed behind and between the condyles. The writer gives it the preference over other amputations through or immediately above the knee. Fig. 174 illustrates the incisions of this amputa- tion and the method of forming the flaps. The inci- sion begins an inch below the tuberosity of the tibia and passes over the outer side of the leg and is carried in a gentle curve to the middle of the posterior sur- face. Here it ends opposite to tin' interarticular line. A similar but longer flap is outlined on the inner side. The flaps are then dissected up and are made to include everything down to the bone. While the flaps are being formed the limb must be maintained in extension. The disarticulation completes the oper- ation, the semilunar cartilages being retained in the stump. In the last forty years a number of modifications of the operations just described have been introduce, 1. They all have the feature in common that a portion of, or the entire condyles of the femur are to be re- moved. In 1845 Syme advised amputation through the condjdes, making a large posterior musculo- tegumentary flap. In 1S46 Mr. Carden first per- formed the operation which has since borne his name, and has become deservedly popular. The operation consists in the formation of a long anterior flap, which, like a hood, falls easily over the divided end of the bone. The incision, similar to that made for amputation at the knee, extends no farther down than the tubercle of the tibia. The anterior flap being re- flected, the joint is opened aboi'c the patella, which is not included in the flap. After disarticulation has been effected, the soft parts of the posterior aspect of the limb are severed by a single stroke of the knife, and the saw is applied through the bases of the con- dyles. For the better coaptation of the cutaneous margins of the wound Lister has advised the forma- tion of a short posterior tegumentary flap. Mr. Carden has recorded thirty operations, with only five deaths from this method. Of twent3'-six Car- den amputations made by Volkmann, three termi- nated fatally. In 1857 Gritti of Milan devised an osteoplastic operation by which the articular surface of the pa- tella is removed and placed in apposition with the divided ends of the femoral condyles. The opera- tion was first practised by Sawostytzki in 1862. In this operation long anterior and short posterior rectangular flaps are formed. Paikrt and Linhart after raising the anterior flap amputate without first disarticulating. In 1870 Dr. William Stokes still further modified Gritti's operation by making an oval flap and dividing the femur at least half an inch 'above the anterosuperior margin of the con- dyloid cartilage. Hence this amputation is gener- ally known as the supracondyloid amputation, that of Carden being known as the transcondyloid operation. A further modification of the Gritti osteoplastic am- putation is that of Ssabanajeff. An anterior and a posterior flap are fashioned in the usual manner bul the knee is opened from behind. After this has been done the leg is hyperextended so that the anterior sur- face of the leg and thigh are in contact. The lower end of the femur is then divided transversely through the thickness of the condyles. Finally a bone flap is made over the upper and anterior part of the tibia to which the attachment of the fibular ligament: is left undistrubed. The sawed surfaces of the tibial bone flap and of the femur an' then brought in con- tact and retained by a suture. The attachmenf of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation the patella is ool disturbed. The relative merits o) these various methods of amputation at the knee have extensively investigated by American, English, .,,„! German writers. Edmund Andrews oi Chicago j thai disarticulation al the knee and transcondy- loid amputation present alike mortality (twentj eight uejcent). Of < rritti's operation and Stokes' modifica- tion Dr. R. F. Weir has collected seventy-six cases with twenty-two deaths. In the reports of the Munich Surgical Clinic, 1895-1907, Paul Weiden- uesch" found there were twenty-three Gritti opera- tions without any deaths, although primary union Ited in only fourteen of the cases. While time may show that the last-mentioned procedures maj ,i service in amputations for disease, sufficient lence has been adduced by Zeiss, Beck, and man, that, so far as military practice is con- cerned, the operation ought to be abandoned. From the mure recent statistics ([noted above for other am- putations, the mortality of amputations at the knee h il practice is 11 per cent., there being seven deaths for sixty-two operations. The mortality of amputations at the knee in civil tice appears from an examination of Table III. above). Of 1S7 amputations made for gunshot injury, in which the result was determined, 10(3 suc- cumbed, the mortality being 56.6 per cent., and ex- ling by 2.8 per cent, the fatality of amputations in the lower part of the femur. Amputation of the Thigh. — This operation may died for in any part of the thigh. The central position of the femur and its extensive muscular ring -auction the application of any of the va- rious methods of amputation in this part. The choice from among the different operations permits um i at all times to save as much of the femur as possible. Until twenty years ago amputation of the thigh was generally performed by the trans- fixion method, by which an anterior and a posterior flap were formed. The rapidity and ease with which it could be performed were its chief commendation-. The manner in which it is generally performed i- the following: Grasping and raising the soft parts on the anterior aspect of the limb with his left hand, the operator introduces the knife at the side of the limb, at a point an inch or more below the level of the Fig. 175. proposed section of the femur, and, carrying it across the anterior surface of the femur, transfixes and cuts out a broad flap equal in length to half the diameter of the limb (Fig. 175, Fergusson). The flap thus formed being retracted, the knife is again introduced into the wound behind the femur, and a posterior :lap formed by cutting from within outward and downward through the soft parts. The flap thus made should be quite as long as the anterior, since the greater retraction of the posterior muscles would otherwise reduce it to a size that would prevent the accurate coaptation of the cutaneous margins of the wound. In very fleshy subjects, all of the muscular Fig. 176. 1 1 ue hould "< i 1 1 1 , and on the left to the trochanter. The sup- puration which was established almost separated the right thigh, the round ligament and great sciatic nerve alone holding it to the trunk. Lacroix, surgeon to the hospital, completed the separation of the member. This operation succeeded so well that four days later he also amputated the left thigh. There was "neither hemorrhage nor pain, and the patient progressed well till the tenth day, when fever supervened, and death followed fifteen days after the first operation." In 1773 Perault removed the entire thigh in a case of traumatic gangrene "of several months' duration," in which a complete recovery ensued in eighteen months. Although in 1774 and 1778 Kerr and Thomson made the first amputations at the hip through living tissues in cases of coxalgia, both operations termi- nated fatally, and the procedure was not again resort- ed to till the last decade of the past century. Ampu- tation at thr hip in reality owes its existence to the wars of the French Revolution. In 1794 the elder Blandin performed it thrice, with one recovery. Dur- ing his different campaigns, Larrey repeated the operation seven times and gave it a standing among surgical procedures, although it is doubtful whether any of his cases recovered. In 1812 and 1815, Brownrigg and Guthrie, after repeated failures, were enabled to report successful amputations at the hip for gunshot injury. The first operation in this coun- try was made in Kentucky in 1S06, by Brashear, for compound fracture, and ended in recovery. 296 The most comprehensive statistics of the operation in question have been collected by Otis, Liming, and Ashhurst. Over three-fourths of all the operations have been made since the introduction of anesthe- sia, and fully two-thirds of the entire number were performed later than 1860. Up to 1875 Liining was enabled to collect but 497 well-authenticated cases while in 1881 Ashhurst tabulated 633 operations' since which time over 100 cases have been added to the list. The question of supreme moment in amputation at the hip joint is that which pertains to a complete anil yet safe method of controlling the circulation during the operation. Its importance becomes mani- fest from the fact that five per cent, of the patients operated on do not survive the operation, and that seventy per cent, of the deaths occur during the fir-t five days (Liining). To overcome this great and im- mediate danger of amputation at the hip, progress has been made in the direction of preserving the blood contained in the condemned part and by temporarily or permanently occluding the sources of its blood supply. By the use of the elastic bandage from the toes to the groin, and by keeping it in place during the operation (Erskine Mason), or, in cases of exten- sive suppuration of the extremity, by maintaining the lat ter in a vertical position for some minutes before the operation, a not inconsiderable amount of blood can be saved to the economy. In I860 Pancoast first called attention to the practicability of compressing the aorta against the vertebral column by means of an abdominal tourni- quet. A number of instruments have since been devised similar to that of Pancoast, by Lister, Skey, and Esmarch, and it is to one of these contrivances that most surgeons have recourse before proceeding to the operation proper. In the tourniquet of Es- march, the aortic pad exerts its compression by mi of an elastic band which is passed through its handle. In the absence of a tourniquet, a pad can be impro- vised by firmly winding a long roller bandage around the middle of a stick, which should be about a foot long and of the thickness of the thumb. The pad thus formed being placed in position, is retained by five or six turns of an elastic bandage around the ab- domen (Esmarch). Spence resorts to a similar pro- cedure. Whatever tourniquet be used, it should be applied while the patient is lying on the right side, the pad being placed a little to the left of the umbilicus (Fig. 178, Esmarch). The operation should not be commenced until the operator has satisfied himself that the circula- tion in the lower extremities is com- pletely controlled. It having been held, but without sufficient clinical evidence, that pro- longed compres- sion of the abdom- inal aorta is injuri- ous from damage to the branches of the solar plexus, and by interfering with respiration, compression of the common iliac artery through the rectum has been advised and practised. A\ - bury of Philadelphia and Van Buren of New- York proposed that this be accomplished by the hand of an assistant, while R. Davy of London devised for the same purpose a polished rod twenty inches long, and from one-half to three-fourths of an inch thick, surmounted at its extremity by an ivory enlargement, with which the artery is to be compressed against the Fig. 178. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amputation brim of tin' pelvis. 1" one case in which Davy used the lever on the right iliac artery, deal h followed from B rent in the rectum. In seventeen other cases in which ho had resorted to its use an accident resulted. \, cording to the originator of the "lever," this instru- ment has been used in forty cases, in an ulnu >-t equal proportion of amputations of the right and left side, and sixty-five per cent, of the ,..(.,.< recovered. Davy 11 has re- ported ten cases with right re- coveries. [ n thin or emaciated Bubjects, the circular (ion can be controlli Fig. 179. by digital compression of the aorta or external iliac artery, or both may be employed (Gross). It may likewise be effected by the use of a wide roller bandage placed over the external iliac and held in position by an elastic bandage. The latter should be about two yards in length, its center being placed between the anus and tuberosity of the ischium; the anterior part of the bandage is brought above the crest of the ilium, the posterior portion crossing the sacrosciatic notch and meeting the anterior above the iliac crest; both are firmly held in position by an assistant. This method of preventing hemorrhage from both anterior and posterior flaps has been resorted to in four cases by Jordan Lloyd of Birmingham; three of the patients recovered. With the introduction of better methods against hemorrhage, the use of the abdominal tourniquet, of Davy's lever, and of digital compression can no longer be advised. In- 1S76 Trendelenburg of Rostock devised a steel rod fifteen inches long, one-fourth of an inch wide, and one-eighth of an inch thick, with a movable point attachment which is to be pushed through the soft parts in front of the joint, an inch above the level where trans- fixion is to be made with the knife. "The rod having been pushed through the soft parts, the point is removed and a rubber tube wound around the protruding ends of the rod in figure-of-S turns. In this manner compression of all the soft parts in front of the joint is effected, and the flap can be made without loss of blood. After the vessels divided in the anterior flap have been ligated, the rod is introduced through the soft parts behind the joint in a similar manner before the posterior flap is made." Although tedious in its performance, this method of controlling hemorrhage is thoroughly practicable and promises good results. It has been successfully resorted to by Varrick in a case of traumatic amputation in a subject very anemic from hemorrhage. In 1890, Wyeth" described a bl Hess amputa- tion at the hip, which, while it appears to be an amplification ot Trendelenburg's method, is exceed- ingly simple, and can be highly recommended for all amputations at the nip, save those rare ca which the di ea e involves the trochanter. In these cases the transperitoneal ligation of the external, or, better still, of the i mon, iliac is to be pre- ferred to the pins and constriction used by Trendelenburg and Wyeth. The accompanying diagrams (Figs. 17U and 180), inserted with Dr. Wyeth's permission, illu trate the method of the introduction of the pins. The patient is placed with the hip well over the end of the table, and an Esmarch bandai is applied. With the bandage still in position, Wyeth's needles are inserted as follows: "Two steel mattress n lie-, t h i eo-sixteenths of an inch iii diameter and a foot long, are used. The point of one is inserted an inch and a half below the anterior superior .-pine of the ilium ^ and slightly to the inner side of this prominence, and is made to traverse the muscles and deep fascia, passing about half way between tic great trochanter and the iliac spine, external to the neck of the femur and through the substance of the tensor vagina' femoris, coining out just back of the trochanter. About four inches "f the needle should be concealed by the tissues. The point of the second needle is entered an inch below the level of the crotch, internally to the saphenous opening, and, passing through the adductors, comes out about an inch and a half in front of the tuber ischii. No vessels are endangered by these needles. The points are protected by corks to prevent injuries to the operator's hands. A piece of strong white rub- ber tube, half an inch in diameter, and long enough when tightened in position to go five or six times around the thigh, is now wound very tightly around and above the fixation needles and tied." The Esmarch bandage is then removed, and if the oper- ation is to be completed according to Wyeth's plan, a circular incision is made, the skin flap is turned up, the muscles are divided at the lesser trochanter, and the bone is sawed through. All vessels are then tied. The remaining portion of Fig. ISO. the femur is then removed by division of the attach- ments of the muscles. The methods of hemostasis above described will probably be supplanted by the constriction of the abdominal aorta by an ordinary rubber tourniquet as devised by Momberg in 190S. It is a method applicable to amputations of the thigh, of the hip, and of the os innominatum. I have used it in high am- putations of the thigh and in controlling the bleed- ing during an aneurysmorrhaphy. It is applied as follows: 297 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The patient is placed in the Trendelenburg position. The end of a piece of soft rubber tubing, having the thickness of the index finger and the length of about four feet, is passed through under the back of the patient to be grasped by the hand of an assistant who stand-; at the opposite side of the operating table. This tube is then stretched to the utmost, and thus stretched, is passed by the surgeon midway between the border of the ribs and the "iliac crests across the abdomen to the other hand of the assistant, whose duty it is to maintain tension. The free end of the tube is now led back under the patient by the sur- geon and is again put on the stretch, the assistant in the meanwhile gradually releasing the bite of the stretched tubing which now firmly encircles the waist. \\ liile this is being done another assistant places a finger on the femoral artery to ascertain the moment of the cessation of the pulse. Observing the same steps,_two, three, or more turns of tubing are exactly superimposed until the femoral pulse disappear-. In slim individuals two turns will suffice; in fat or muscular ones, as many as six may be necessary. As soon as the femoral pulse is suppressed the ends of the tube are crossed and secured by forceps or ligature. After this is done constrictors are applied to the thighs below Poupart's ligaments, and to the legs below the popliteal spaces. As soon as the operation is finished and all the vessels have been secured by ligatures, the rubber band encircling the waist is re- moved. Directly after this the other rubber liga- tures embracing the thighs and legs are untied one by one. The object of this is the gradual extension of the scope of the circulation and the avoidance of a too sudden demand upon the efficienc}- of the heart muscle. By this switching on of one segment of the circulatory system after another, the readaptation of the heart to the changed conditions is gradually effected. Two dangers would seem to attend the tubular con- striction of the aorta; namely, the sudden lowering of blood pressure on removal of the tourniquet and injury to the intestines. How to avoid the former has already been shown. The second is averted by having the bowels thoroughly emptied and by placing them out of reach of the tourniquet, by using the Trendelenburg position. Mayer 18 has recorded nearly 200 cases in which it was used, and in only two was there damage to the intestines. Matas* 20 experi- mented on eight healthy students without any ill effects. Fig. 181. Methods. — Although a large number of methods of amputation at the hip have been devised (according to Ashhurst there are forty-five), only a few of them are of practical value, and are, therefore, commonly employed. The methods which will be considered are, that by musculotegumentary flaps, that by cutaneous flaps and circular division of the remaining soft parts, and that by a high circular amputation with subsequent excision. 298 Musculotegumentary Flaps. — Amputation at the hip can be most quickly accomplished by means of anteroposterior muscular flaps, of which the anterior is made by transfixion, and the posterior by cutting from within outward. With able assistance the operation can easily be performed in less than twenty seconds. At least three assistants are required in this, as in all amputations of the hip. One of these is entrusted with the control of the circulation in the limb, the second follows the knife to grasp the flap before the artery is divided (Fig. 181, Hueter) and then to retract it, and the third takes charge of the condemned limb. Fig. 182. The patient's body having been brought to the foot of the table, the nates are made to project over its edge, and the scrotum and sound thigh are held out of the way. While the condemned limb is slightly flexed, the operator, standing on the left side, enters the point of an amputating knife, the blade of which is at least a foot long, midway between the anterior superior spinous process of the ilium and the trochan- ter major. It is carried deeply into the limb in a direction parallel to Poupart's ligament, across the anterior surface of the joint, which is thus opened, and made to issue on the inner surface of the thigh close to the perineum and just in front of the tuberos- ity of the ischium. Transfixion accomplished, a broad rounded flap, five to seven inches in length, is made by carrying the knife downward in front of the bone and cutting outward. This flap is at once reflected and held out of the way. By a transverse incision on the head of the bone the capsule is then widely opened, while the limb is forcibly abducted and everted. Hyperextension then causes the head of the bone to start from its socket with a " popping'' noise when the ligamentum teres is cut. The knife being then introduced behind the head of the femur, the posterior portion of the capsule is divided and a posterior flap four inches in length is cut from within outward (Piston). When the operation is made on the right side, the knife is entered from the inner side just above the ischial tuberosity. When the poster- ior flap is cut from within outward the cutaneous margin of the wound is generally irregular and not well_ suited for close coaptation with the anterior flap. It is advisable, therefore, particularly in robust limbs, .either to outline this flap by an incision through the skin, or to cut it altogether from without inward (Fig. 182, F.smarch) (Manec). Indeed, both flaps may advantageously be cut in this manner (Guthrie). The great advantage of the operation just described is in the rapidity with which it can be executed. Its disadvantages are in the excessively large wound which it leaves, the tendency to the retention of pus REFERENCE HANDBOOK OF THE MEDICAL SCIENCES A mputatlon in the intermuscular spaces, and the great probability 3 ive hemorrhage from the posterior flap. \ W ound better suited for drainage is thai made by lateral flaps In this form of operation a semicircular incision is made, beginning at the tuberosity ofthe : chium and terminating on the outer side oi the femoral vessels in the center of the groin. The incision crosses the outer surface oi the thigh four or five inches below the trochanter. The flap thus outlined is then reflected over the latter and the joint tied. The inner flap is then made by cutting from within outward. , . , , gumentary Flap Method. — Tins is an admirable method to overcome the superfluity of muscular tissue in the wound and the consequent tendencj to purulent infection, and it is therefore preferred by a number of operators, among whom are Agnew and Volkmann. The operation is described by Agnew Hows: "The surgeon makes a semilunar incision in front of the limb with its convexity downward commencing midway between the anterior sup- erior spinous process and the trochanter on the outside, descending the thigh in a longitudinal urn for five inches, then passing across the front of the limb in an oval course, adding thereby an inch to the length of the flap, and, lastly, ascending the inner border of the thigh, and terminating one inch below the ramus of the pubes. The integument ,v rapidly dissected up from the deep fascia and isted to the lingers of an assistant." The next step is to isolate the femoral vessels above th, origin of the profunda and to apply separately to the artery and vein a strong ligature. Volkmann divides the vessels between two ligatures. By dis- placing the pectineus muscle the obturator artery can be readily found and ligated below the obturator membrane. The limb being now raised, the surgeon proceeds to cut a semilunar tegumentary flap from the back of the thigh, one inch shorter than the anterior. With amputating knife the muscles are then severed circularly in front of the joint, "when after liberation of the head of the bone, as in other methods, the operation is completed by dividing through the soft parts posteriorly. According to Agnew, this opera- tion can be completed in forty seconds. Circular Amputation. — In order to make a smaller wound, and to divide the vessels where they are .smaller, a circular amputation of the thigh at the lower part of the upper third is made. This may be accomplished by a single incision in thin subjects, while in robust extremities it is preferable to resort to a double incision. When the amputation in this part is effected, all the blood-vessels that can be recognized must be ligated. An incision is then made along the outer side of the stump from a point two inches above the trochanter to the circular wound, and dividing everything down to the bone (Dieffenbach). The operator then seizes the stump of the femur with a lion-jawed forceps, and while the edges of the vertical incision are separated by an assistant, the soft parts, including the periosteum, are stripped from the bone, and the capsule is opened and disarticulation effected as in other procedures. Fig. 179 from Wyeth shows the circular amputation Wound with pins in situ and before the head of the bone has been removed. In 1S80 Mr. Furneaux Jordan of Birmingham published a method of amputating at the hip which docs not differ essentially from the method just described. In his operation the outer incision is first made, disarticulation is effected, and the circular incision forms the last step of the operation. finally, mention must be made of the methods of Verneuil and Ed. Rose, and of Senn, 21 who in ampu- tating at the hip treat the lower extremity as they Would a neoplasm that is to be removed, cutting from Wi! hout inward and tying each vessel as it is encoun- tered. A shorter internal and longer external inci- sion is made through the skin wnen the femoral artery and vein are to lie divided between two ligatures. The incisions are then gradually carried through the muscles in front and on the outer side until the articulation is reached, when, after dis- articulation has been effected, the addueted muscles are divided last of all. Amputations at I he hip of nece it y pre ent a deplorable mortality. Of 633 ca e tabulated by Dr. 1'. C. Sheppard for Ashhurst, 393 terminated fatally, and in twenty the result was undetermined. The general mortality of the operation is, therefore, sixty-four per cent. The most unfavorable results obtained are those from military practice. Of 249 cases of this character in which the result was ascer- tained, including sixty-six operations performed during the War of the Rebellion, only twenty-seven patients recovered, the mortality being 89.1 per cent.; twenty-five of the sixty-six cases referred to were primary amputations, of which three recovered; twenty-three of the operations were secondary, and all terminated fatally. Of nine secondary operations, two survived, and of nine reamputations, six recov- ered. Of seventy-one cases of hip-joint amputation for injury in civil practice, forty-seven died, the mortality being 60.1 per cent. Of 270 cases of hip- joint amputation for disease, of which fifteen were undetermined, 105 terminated fatally, the mortality being 40.2 per cent. Owing to the improved methods of preventing hemorrhage, and particularly through the use of Wyeth 's method, the mortality of amputations at the hip has been very greatly reduced. Wyeth- 2 collected sixty-nine cases with only eleven deaths. Of the fatal cases, five had severe injuries. I have collected 138 cases of amputations at the hip, pub- lished between 1889 and 1900, including the sixty- nine cases collected by Wyeth. The total mortality of the 139 cases was twenty-seven, giving a mor- tality of a little over nineteen per cent. Of the amputations there were 121 for disease with twenty- one deaths — in this estimate I include three cases of my own, one of which was fatal — or a mortality of seventeen per cent. I find that six amputations were done for injury, with only one recovery — the cases reported by McBurney. In fifteen cases the cause for the amputations was not stated; of these one died. Interilio-abdominal Amputations. — The indi- cations for interilio-abdominal amputations have thus far been neoplasms of the upper end of the femur and of the pelvis and intractable tuberculous coxitis involving the acetabulum and the iliac pan. The first operation was performed in 1891 by Billroth and ended fatally in a few hours. Extensive con- sideration of the operation was given after the report of three operations by Jaboulay. The original operation of Jaboulay consisted of making one large posterior flap. The first incision was made from the symphysis parallel to and over Poupart's ligament and the entire length of the iliac crest. By retracting the upper wound margins the soft parts are lifted from the iliac fossa, and the vessels easily reached for tying. A circular incision is next made at the upper third of the thigh, through the center of which, on the anterior surface, the two incisions diverge toward the pubes and the iliac crest. Thus a very large posterior flap is left which completely and easily covers the wound. Girard operated in three cases by making internal and posterior flaps, Bardenhauer formed external and internal flaps, and Salistcheff in his successful case operated by the racquet method. His incision begins below the twelfth rib and passes over the anterior superior spine of the ilium to Poupart's ligament, which it follows to the pubes. Through this incision the vessels are secured. The wide end 299 Amputation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of the racquet incision sweeps over the buttock to the point of starting. The simplest method, from an operative standpoint, is that of the long internal flap the method of Savariaud slightly modified by Keen and adopted by me. It has the signal disadvantage Of having to be exceedingly long to cover the wound, ihe risks of gangrene I believe to be larger after this operation than after any other. Where it is feasible it appears to me that the incision of Salistcheff has superior advantages. Interilio-abdominal amputation must always re- main a desperate operation. It should not be re- sorted to where a less mutilating procedure is possible artial resection of the os innominatum for tumors of the iliac pan ought to be performed in preference to the mterilio-abdominal amputation. Strange as it may seem the three complete hemipelvic resections performed by Kocher (2) and Roux (1) all recovered. Whereas according to Croisier, of the partial resection there were eight deaths and seven operative recoveries. It is need ess to add that these conservative operations have a place only for limited neoplasms. So far as the usefulness of the ilium is concerned in hemiresec- tion of the pelvis, there has been less impairment of stability and usefulness than one might imagine in the cases of interiliac amputation that have sur- vived, there has been no tendency toward eventra- tion, a condition which one would judge to be a cer- tainty after removing so much of the bony support of the abdominal viscera. Table I.— Operations in One Stage for Sarcoma. '. Bi "roth (1891). Death in a few hours. Verbal communi- call.Mi. .-.nvari.-iud. It, -v. dc Chir., vul xxvi p ,T,0 i»oi Jab ^ ay (1S94) - Deathin thirty-six hours! Lyon Med ioLr-i, p. o07. ,, ; , J ;'':,' ull ,y (1 , S ? 5) - Death in twenty-four hours. Province 4. Jaboulay (1895). Death in five days. Girard, verbal com- munication (Pnrigle). 5. Cacciopoli (1894). Death in three hours. Centralbl f Chir. (quoted), 1S94, p. 988. 6. Gayet (1S95). Death in one hour. Province Me, 1 1894 J\o. XXXV. ' 7. Girard (1895). Recovery. Congres Chirurg., 1898 8. *aure (1S99). Operation abandoned. Savariaud, Rev do Chir., vol. xxvi., p. 365. 9 Freeman (1S99). Recovery. Annals of Surg., vol. xxxiii., 10 Nann (1900). Recovered from operation. Gangrene of other leg. Congres. Intermit. Paris, 1900 _ 11. SaUstcheff (1900). Recovery. Arohiv. f. klin Chir vol ix., p. 57. ' ' 12. Savariaud (1901). Death in two hours. Rev de Chir vol. xxvi., p. 360. 13. Gallat (1901). Death in one hour. Annal.de Chir .Beige) vol. ix., p. 569. " nJ*' Jir"", (19 ° 2) - Dea,h in nine h " ur «- A »*- Gen. de Chir., 1903, vol. cxii . p. 1665 15. DeRuyter (1902). Death in an hour. Henri Myer, Inang Thesis., Leipzig, 1902. , J 6 ' ^ e ™,. and DaC °Sta (1903). Death in thirty-three hours internal. Clinics, vol. lv., Series 13. Chir" no''' 1 ''' I™'' Death ° nBeCOnd day " Jahresbericht f. Chir' 190°' ler 003° 3> ' De '' lth °" SeC ° nd day - Jahresberi <*t f- 19. Lastaria (1907). Died „,, table. Reiforma Med Nanoli vol. v., p. 457. Chir' ?902 W IK)!'' I '' VOd thir ' y " five days - Jahresbericht f. , n ™ Bi tC (190S) - R «=overy. Momburg., Centblt. f. Chir 22. Ransohoff (1909) Recovery. Lived thirty-eight days. Anuals of Surg., Nov., 1909 It will be seen from Table No. 1 that the post- operative mortality of this amputation "the mosl extensivfe operation in all the realm of surgery " is sixty-eight per cent., counting the cases of death' after * In a personal communication Prof. Bier informs me thai his patient died two months after operation, of recurrence in the abdominal wall. twenty days with the operative recoveries I have followed the lead of Keen. In 'the ca,^ where the resection of the pelvis was preceded bv amputation at the hip, no deaths followed the tlnd operation. From this it might be inferred iu tins course is preferable as a routine procedure r„ fortunately in tumors of the pelvis the two-staaa operation is not feasible and in those for tuberculosis none other is ordinarily applicable. In the c! corded by Freeman, the amputation at 1 . | •' ^mediately followed by resection of the pelvb Ihe ex en of the disease was evidently not apparent' until the hip-ioint amputation had been done In the cases of Girard and Pringle the second operations at'tlu n hi p recurrent di * ase ^ter disarticulat^ Doleful as are the immediate results of interilio- abdominal amputation, the end results have been even more unpromising The cases of Girard classed with recoveries, died within six months of recurrent Pringle s case died in five months with metastases! Salistcheff's case was reported well within four months of the operation. The end result I do not know. I he record case is probably I hat of Freeman Although he left the anterior third of the acetabulum and of the ilium, the case belongs in the category o intenho-abdominal amputations. Freeman's patient was well at the end of sixteen months, when reported but died twenty months after operation from recur- rence in the abdominal wall (personal communica- tion). Of the end results of the operation for tuber- culosis, the data are extremely meager. The case of Bardenheuer gained in health and strength four months after the operation, and it is presumed was a permanent recovery. The case of Pringle was with- out recurrence seven years after the operation. Table II.— Operation in two Stages for Sarcoma. 1. Girard (1S95). Amputation at hip. Some months later resection of pelvis. Recovery. Rev. de Chir., vol. xxvi ,, : 6 S .f^"™; 1 ll f S) : Amputation at hip. Death six months alter reaecUon of os innominatum. Lancet, Feb. 20, 1909. In the face of these unpromising results, it may be questioned whether the operation is justified 'Tic same question has been put for every major operation in surgery, and has in the course of time with un- varying uniformity been answered affirmatively By limiting the operation to suitable cases and per- orming it at a time when there is at least a probability that the patient can bear the shock connected there- with, it is almost certain that the prognosis will improve as it has so markedly for amputation at the up. _ Disseminating the knowledge that the opera- tion is feasible will, by bringing the eases earlier to the surgeon, contribute much toward this desirable end \\ ith two exceptions, I know of no text-book in which the operation is even mentioned. Table III. — Amputations for Tuberculosis.* 1. Girard (1S95). I lied in fifty minutes. Rev. de Chir 1S98 p. 1111. 2. Bardenheuer (1897). Recovery. Gesellsch. d. Chir., xxvi I, p. 130. 3. Gallet (1900). Died in six hours. Gesellsch. d. Chir xxvi I, p. 130. 4 Ribera (Madrid) (1902). Died, collapse. Luis y Simon Siglo Med., 1903, vol. v, 5. Ribera (1902). Died eighth day. Luis y Simon, Siglo Med., 1903, vol. v. 6. Ribera (1902). Died, collapse. Luis y Simon, Siglo Med 1903, vol. v. 7. H. Vermeuil (1905). Died in two hours. Jour de Chir (Beige)., vol. v., p. 406. The operations for tuberculosis were practically all done in two stages, the first being either a hip resection or amputa I he extent ol the resection of the pelvic bone varies much. I have, however, excluded all cases in which the resection did not involve the major part of the ilium. 300 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Amygdala 8 Morestin (1908). Recovery. Bull. Soe. de Chir., Paris, vol n\i v i P ""'" ., pringlo 1908) R very. Lancet, Feb. 20, 1909. 1908). I >< iii' on in i day, Lanoet, Feb. 20, M r. Fiaschi. Recovery. Australian Med. .lour., Deo. 23, 1911. In an operation of such magnitude, the initial mortality is largely due to hemorrhage and to shock. i if all the cases thai arc not included under postopera- tive recoveries, only two survived the fourth day. The prevention of hemorrhage has in mosl rases been ;.i ii\ preliminary tying of the common iliac, internal iliac, or the external iliac. Many believe the tying of the corresponding veins ought always to be practised. Kocher and Kadjan encoun- i severe venous bleeding. Tying of the thin- walled large veins doubtless would increase the diffi- culties of the operation. Fame, after a, median my, applied a temporary ligature to tin- aorta below the common iliac. Nevertheless, a severe venous hemorrhage from subcutaneous and subperi- toneal veins necessitated abandonment of the opera- tion. Xanu, Jaboulay, Cacciopoli, and Salistcheff also ligated the common iliac. Bardenheuer tied h i he external and the internal iliac vessels. Free- man lied the external iliac and, later in the operation, common iliac. Keen tied the internal iliac artery. by the tying of the common iliac artery pre- ventive' hemostasis can be accomplished, has been amply demonstrated in the case reported, and it was satisfactory. Unfortunately where a long nal Hap is, as in our case, a matter of necessity, there is great danger of gangrene. This had already commenced in Keen's case, although the patient lived only thirty-three hours. The gangrene strangely loped in the superior flap and not in the margin ot the long internal. In my ease the gangrene in- volved the long flap only. Were a similar case to e under my observation, I would tie the external iliac and the posterior trunk of the internal. In that manner the obturator artery would be left intact for tin- nutrition of the long internal flap. Joseph Ransohoff. Bibliography. 1. Hippocrates: Sydenham Society edition, vol. ii., p. 639. 2. Paulus Aeginetus: Sydenham Society edition, vol. ii., p. 110. 3. Billroth nnd Pitha: Handbuch der Chirurgie, vol. ii., !, Abth. 2, p. 19. 1 Agnew: System of Surgery, vol. ii., p. 305. .".. Burow: Deutsche Klinik, 18.36. 6. Gueterbock, P.: Archiv fur klinische Chirurgie, Bd. x\\, and stvii. 7 Gross: System of Surgery, voL i., p. 530. 3 I rdmann, .1. F.: Annals of Surgery, vol. xxii., p. 358. 0. Paget: Lancet, 1S95, i., p. 023. 10. Bruns: Beitrage z. klin. Chirurgie, vol. xxii., p. 2. 11. Barling: Clinical Society Transactions, xxxi., p. 1S2. 12. Moschcowitz: Annals of Surgery, vol. xxxix, p. 794. 13. Ilalm: Beitrage zur klinischen Chirurgie, vol. xxii., part 2. I I. Bier: Deutsche Zeitschrift fur Chirurgie, vol. xxxiv., p. 436. 15. Smith, Stephen: Am. Journal of the Med. Sciences, vol. Kix, ii :;;, 1S70. III. Weidenpesch, Paul: Dissertation, Munich, 190S. 17. Davy: Lancet, 1892, ii., p. 570. is. Wyeth: New York MedicalJournal, 1890, ii., p. 528. 19. Mayer: Journal de Chirurgie, 1910, p. 121. 20, Matas: Transactions of the Am. Surgical Association, vol. xxviii., 1910, p. 622. -'1 Senn: Chicago Clinical Review, 1S92, p. 343. 22. Wyeth: Annals of Surgery, vol. xxv., p. 129. Amussat, Jean Zulema. — Born at St. Maixent, France, November 21, 1706. He studied the rudi- ments of medicine under his father, a physician, com- pleting his education at Paris. His earlier medical life was devoted chiefly to anatomy which he taught to artists as well as to medical students. While FIG.1S3. — Jean Zulema Amussat. preparing for a concours in competition for appoint- ment to a professorship he acquired an infection which nearly ended his life and left him invalided for so long thai he was forced lo give up the public teaching of anal y. On recovering his health hi? turned his attention lo surgery in which he -nun acquired fame, lie was an indefatigable worker, a skilful Operator, an orig- inal thinker, and in- genious in devising new operations and in the i n ve n t io n of instru- ments. While an in- terne at the Salpetriere he invented a rachitome for exposing the spinal cord. He developed tin; operation of lithotrity, .Ii > ising a probe, which st ill bears his name, for i e in locating and steadying the stone in thai procedure. He ga\ e his name also to theoper- aiion for lumbar colos- tomy in the ascending colon. He was the recip- ient of several grants, aggregating 1,500 francs, from medical and scientific bodies in recognition of his labors in advancing the science and art of surgery. He died .May 13, 1856. Amussat was a most prolific writer of monographs and journal articles on a great variety of gynecological and surgical subjects, his most extensive work being a treatise on "Torsion des Arteres," published in 1829. Other minor works were on the Entrance of Air into the Veins, and on his special operations of Lithotrity and Lumbar Colostomy. T. L. S. Amygdala. — Almond. A. dtjlcis. Street almond. The ripe seed of Prunus amygdalus dulcis D. C. (Fam. Rosacea:). (U. S. P.). A. aiiaha. Bitter almond. The ripe seed of Prunus amygdalus arnara D. C. (Fam. Rosacea). The almond tree is a native of the east Mediterra- nean region and is now cultivated in all warm- temperate regions, especially in California. The tree, with its leaves and flowers closely resembles the peach. The fruit differs in being dry instead of fleshy, and in splitting to discharge the stone, which, with its contained seed, is the unshelled almond of commerce. The shelled almond is the article here considered. The bitter almond is probably the original wild form, from which -the sweet has been derived by selection, breeding, and cultivation. There are so many forms of both the sweet and bitter varieties that it is useless to attempt any differential description of the two, except as to order, tests, and constituents. Those used as drugs are about an inch in length, ovoid, with strongly rounded base and obtusely pointed apex, flattened so as to be three times as broad as thick, and about one-half longer than broad. The surface is of some shade of brown, more or less wrinkled, scurfy, with a dense covering of short, thick, microscopical hairs, and with numerous lines radiating from the base. The kernel consists entirely of two oily cotyledons of the same form as the seed, in contact by their flat faces, and of a nearly white color. The bitter almond has a characteristically bitter taste, the sweet ones being entirely bland, sweet, oily, and nutty. Of sweet almonds, the important constituent is fifty per cent, or more of a fixed oil (see Oleum Amygdala- Expressum), which occurs with about three per cent, of gum and six per cent, of sugar, and a large amount of albuminoid matter. There is a very small amount of tannin in the seed coat. Their 301 Amygdala REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Eroperties are purely demulcent and nutritive. We ave an official emulsion and a syrup, which are used as vehicles. In composition, bitter almonds have about one- sixth less of the same fixed oil, and contain from one to three per cent, of a peculiar glucoside (see Amygdalin and Emulsln) which yields hydrocyanic acid and benzaldehyde, as described under Hydrocy- 1. ■id. The yield of oil of bitter almond is about one per cent., that of prussic acid about .00 to .18 of one per cent., of the weight of the seeds. It is evident that the bitter almond combines the properties of sweet almonds and prussic acid, and that an ounce of the drug is equivalent to almost one grain of the latter. It does not follow that the effect would be the same as that dose, inasmuch as the development of the acid would be neither so sudden nor so complete. Nevertheless, bitter almonds must be regarded as poisonous. Even a small number of them, if eaten, are apt to produce a slight gastric irritation as an after effect. Their chief use is a flavoring agent, though small doses are used for their sedative effect. Peach seeds are often used to adulterate bitter almond, and their composition is very similar. Sweet almonds are also used as an adulterant. H. H. Rusby. Amygdalin. — The source, occurrence, and general nature of amygdalin will be been stated in discussing hydrocyanic acid. It is not official and is scarcely used in its own form, although occurring in com- merce. Boiling alcohol is used to extract it from almond oil cake, after which it is precipitated by ether. It occurs in crystals or scales which are soluble in twelve parts of water. It is odorless, but very bitter. If entirely free from emulsin, it does not yield prussic acid and is not poisonous. H. H. Rusby. Amvlene Chloral. — Dormiol, chloral-dimethvl- ethyl-carbinol, C(CH,) 2 C s H 5 OH.CCLCOH, is a coin- pound of one molecule of amvlene hydrate and one molecule of chloral. It is a colorless, oily-looking liquid, with an aromatic odor and a pungent, followed 1>\ cooling, taste. It is practically insoluble in water, and is freely miscible with alcohol, ether, acetone, and volatile and fixed oils. It goes under the trade name of dormiol, and is claimed to be a certain hypnotic without depressing effect on the heart or respiration. Its dose is njf. viii.-xxx. (0.5-2.0), given in syrup, or in emulsion with a small amount of olive or almond oil, and flavored with lemon or cinnamon. R. J. E. Scott. Amvlene Hvdrate. — Tertiary amyl alcohol, di- methyl-ethyl-carbinol, (CH 3 ) 2 C,H-.COH. This is a clear, colorless, thin, neutral liquid, with a burning taste and an aromatic odor somewhat resembling camphor. It is soluble in eight parts of water and in alcohol, ether, glycerin, and oils; specific gravity. 0.812 at 53.6° F. It has been recommended for its soporific properties. Its advantage over chloral is, that it has no depressing effect on the heart. Its smaller dose and less disagreeable odor make it preferable to paraldehyde in many cases. It is a rather mild hypnotic, producing a calm, refreshing sleep, which lasts for six or eight hours, from which the patient awakens without any bad symptoms. It has not proved of use when the sleeplessness is due to pain. In very large doses it produces coma, a lowered temperature, shallow 7 respiration, feeble and iregular pulse, loss of reflexes, and paralysis of the extremities, its poisonous symptoms resembling those of alcohol and ether. Its taste and odor often prove objectionable, but may be disguised by extract of licorice, syrup of lemon, lemonade, or some aro- matic. Occasionally it is administered by rectum in solution in water. Its dose is tin xxx.-xlv. (2.0-3.0) but administered in capsules. A case of poisoning has been reported. The patient who had taken 27 grams (about 4oo grains), « L ,< stimulated with mustard plasters and inject inns ,,f ether, and recovered. R. J. E. Scoi i. Amylene. — Valerine, C 5 H l0 . Amylene is a volatile and inflammable ethereal fluid of an unpleasant odor resembling that of cabbage. It was experimented with by Snow in 1856, as an anesthetic, and prove I itself powerful, after the manner of chloroform; but proving itself also capable of killing, it never came into accepted service. R. J. E. Scott. Amyl Iodide. — Iodamyl. C\,H„I, is an oily liquid obtained by distilling together iodine, isoamyl alcohol, and red phosphorus. It is purified by washing with water and redistilling. This liquid is about as heavy as chloroform, boils at 148° C, is freely soluble in alcohol, and insoluble in water. It is used for the same purpose as amyl nitrite in asthma and angina pectoris, but has distinctly less effect in relaxing the arterial muscle. Dose, r^ ii.-v. (0.13-0.3) by inhalation. W. A. Bastedo. Amyl Nitrite. — Amylis nitris, a liquid containing about eighty per cent, of amyl (chiefly isoamyl) nitrite (U. S. P.). It is a yellowish, ethereal, very volatile liquid, of a not disagreeable fruit-like odor and pungent taste, insoluble in water but soluble in alcohol and ether; it is neutral in reaction, but becomes acid on exposure to air, and should be kept in well- stoppered containers away from the light. When inhaled or administered by the mouth or hypoder- mically, it causes rapid heart action and flushing of the surface, dilating the vessels and reducing blood- pressure, and induces general muscular relaxation. 1 1 is employed by inhalation in asthma, dysmenorrhea, muscular spasm, and especially in angina pectoris. For the latter purpose pearls of very thin glass, con- taining three minims (0.2), are prepared; thesi be crushed in the handkerchief and the fumes inhaled to cut short an attack. The dose for inhalation is usually from two to five minims (0.13-0.3). Fi fuller discussion of the physiological action and therapeutic uses, see Nitrites. Amyl Valerate. — Amyl valerianate, apple oil, apple essence, C 5 H 11 C 5 H 9 2 , is obtained by the action of valeric acid on isoamyl alcohol, in the presence of sulphuric acid. It is a clear, colorless liquid, lighter than water, having an odor like that of apples and a sharp ethereal taste. It is insoluble in water, soluble in alcohol and ether, and it boils at 18S°-190° C. Amyl valerate is used in place of valerian in func- tional nervous disorders, especially hysteria. As il is a solvent for cholesterin, it was thought to have the power to diminish the size of gallstones, but il ia hardly probable that this solvent action could take place in the system. In fact, alcohol and other cholesterin solvents taken in large quantities ha\ effect whatever on the size of the stone. Amyl valerate is administered in dose of n\ ii.-v. (0.13 I in capsules, or in five-per-cent. alcoholic solution with an equivalent quantity of amyl acetate. W. A. Bastedo. Amyloid. — From i/ivKov, starch, and efSos, resem- blance, so called from the fact that the amyloid sub- stance gives with iodine and sulphuric acid a reaction 302 REFERENC] EANDBOOK OP THE MEDICAL SCIENCES i 1. .1.1 similar to that of starch. Uso called chondroid, ■ lardaceou or albuminous degeneration. French, p iloide; German, Amyloidentartung, ii. mg. lii,- term amyloid degeneration is applied to the appearance, in the body, of a clear, colorless, shining, homogeneous, highly refractive, and translucent body, greatly resembling wax, firm in consistency, and possessing but little elasticity. Winn treated with iodine solution, it takes on a mahogany color, which in marked cases may become bluish or green Plate VII.). If the specimen thus treated is further subjected to the action of dilute sulphuric acid, zinc or calcium chloride, the mahogany color may be ed, or a play of colors — red, violet, blue, or i may be produced. This reaction, however, docs not always occur. iuse of this characteristic reaction with iodine, nalogous to that of starch, Virchow was led to believe that the newly discovered substance was oid of nitrogen and closely allied to cellulose or starch, and for this reason gave it the name amyloid. It was further designated as "animal cellulose." On the other hand, Meckel believed it to be closely related to cholesterin. Several years after, the chem- ical investigations of Friedrich, Kekule, Schmidt, .-new, and Kuhne proved conclusively that the so-called amyloid was in reality a nitrogenous body u albuminous nature. According to Tscher- niak, it is a coagulated, albuminous substance, and i- possibly an intermediate product between the pro- tein- on one side and fat and cholesterin on the other. The exact chemical nature of amyloid is not yet known. It is very probable that its chemical con- stitution is not the same in all organs, and that it represents different phases of a progressive metamor- is of albumin. The great variation shown in the different staining reactions of amyloid speaks is favor of such a view. In the amyloid isolated by means of digestion of amyloid organs, there is always found a certain amount of ehondroitin-sul- phuric acid, and recent writers have, therefore, re- garded amy I. .id as a compound of a basic albuminous body and this acid. The latest researches by Haus- 1908) do not favor this view; according to his in- vestigations the amyloid isolated mechanically from sago-spleens contains no chondroitin-sulphuric acid. Bo that this substance cannot be regarded as an essential component of amyloid. Nevertheless the in ijority of amyloid tissues show an increased con- tent of chondroitin-sulphuric acid. Lipoids soluble in alcohol are also usually obtainable from amyloid. A irding to Krakow there occur normally in the wall of the aorta of the horse, in the ligamentum nuchas of cattle, and in the spleen and stomach-wall of calves, combinations of chrondroitin-sulphuric acid closely related to amyloid. The writers who accept Krakow's view that amyloid is a combination of a protein and chondroitin-sulphuric acid would, therefore, class amy- loid as a glycoprotein allied to cartilage and yellow elastic tissue. Experimental feeding of chondroitin- sulphuric acid salts does not give rise to the formation of amyloid. Amyloid bears also a very close chemical relation to the hyaline deposits found in blood-vessels and eon- nective tissue, as is shown by the fact that amyloid organs sometimes contain hyaline masses in no way distinguishable from the neighboring amyloid ex- cept by the application of specific staining methods. In some cases the periphery of large masses of amyloid gives the reactions for hyalin and not for amyloid. Litten found that pieces of amyloid tissue lost their characteristic reactions and became changed to hyalin when introduced into the abdominal cavity of animals. The strong general resemblances be- i ween the two bodies, their similarity of location, and the frequent coincidence of occurrence make it very probable that the two substances are so very closely ed thai they 1 1 1 : i \ cha uge from Oni it her. ie writers regard the coincidence of hyalin and amyloid as accidental and reject the view thai the formation of hyalin may be a preliminary step to the de\ elopment of amyloid. Amyloid differs from other albuminous bodies in its characteristic .staining reactions, in its resistance to tin- action of pepsin, and in its very slight tendency to putrefaction. When exposed for a long time t,i the action of gastric juice ii slowly dissolves, so that it is po ible that its resistance to pepsin and agents of putrefaction is due to its great den ity, which hinders the penetration of fluids. It is likewise resistant to acids and alkalies, and is not altered by alcohol and chromic acid. Through the prolonged action of di- lute sulphuric acid tyrosin and leucin may be obtained from amyloid, its end products thus harmonizing with its albuminous nature. Hut little is known with certainty regarding the causes and nature of amyloid formation. It is one of I lie most common pal holoL'i eal conditions of the body, and may exist as a local change, or be widely distri- buted through many organs and tissues. It usually occurs as a slowly progressive disease in association with various cachectic conditions. In these eases of widespread formation it must be the result of some general disturbance of metabolism. The amyloid substance does not exist in the blood as such, but the material from which it is formed may be derived from the blood, or some ferment circulating in the blood may cause a fermentative coagulation of albuminous substances outside of the vessels. Though called amyloid degeneration, the process is not to be classed with the true degenerations of cell protoplasm, but is rather to be regarded as a pathological deposit, in the tissues, of a substance derived from the circulation. It has been conclusively shown that the cells of the affected tissue take no active part in the formation of amyloid. The location of the deposit is practically always in the walls of the blood-vessels or in the inter- stices of the tissues immediately around the vessel-, and the organs which show the greatest degree of the change are those abundantly supplied with blood, as the liver, spleen, and kidneys. It is possible that the amyloid substance is the result of the union of some albuminous material derived from the blood with some constituent of the tissues, and that the lowered vitality of the tissues resulting from general or local disturbances of nutrition favors its formation; or, as the result of impaired nutrition, a peculiarly modified albuminous body may be separated from the blood through the activity of the secretory cells of the blood- vessel walls. As the chief seat of the amyloid deposit is always just outside the endothelium of the blood- vessels, it becomes highly probable that it is a product of endothelial cell activity, and is deposited in the tissues outside the endothelium in a manner analogous to the deposit of hyalin, lime salts, or silver pigment. This pathological secretion may be the result of general changes in the circulation whereby the secre- tory function of the cells of the vessels is changed, or the changes may be primary in the cells themselves. The fact that local deposits of amyloid occur without apparent general changes of nutrition favors this view. Another probability is that the formation of amydoid outside of the blood-vessels depends upon the action of a ferment derived from the blood, this ferment causing a coagulation and precipitation in the damaged tissues of some decomposition product of albumin. Of the origin of this ferment nothing is known. According to Davidsohn it is probably formed in the spleen, since experimental amyloidosis cannot be produced in splenectomized white mice. In the widespread deposit of amyloid in cachectic conditions the pathological condition of the cells may be pro- duced by the altered state of the blood or by toxins; in the local deposits it may be due to local changes in the vessels, caused by local inflammatory processes. 303 Amyloid REFERENCE HANDBOOK OF THE MEDICAL SCIENCES In the majority of cases the deposit of amyloid appears as a secondary phenomenon in various cachectic states, being most commonly associated with chronic tuberculosis of the lungs and bones, chronic staphylococcus osteomyelitis, chronic suppurative processes, syphilis both congenital and acquired, chronic dysentery, and leucemia. In these diseases the most extensive deposits may be found. It rarely occurs in the cachexia of carcinoma, and usually only when there is ulceration of the growth. Amyloidosis has also been observed in cases of hypernephroma. 1 1 is also found, though less frequently, in association with pseudoleucemia, chronic arthritis, nephritis, chronic diarrhea, typhoid fever, prolonged malaria, chronic gonorrhea, chronic empyema, chronic bron- chitis, bronchiectasis, pyelitis, gout, lead poisoning, beriberi, actinomycosis, hypertrophic cirrhosis, and after severe forms of rachitis. Occasionally there may occur in children a widespread deposit of amyloid without any discoverable cause. According to Cohnheim, amyloid deposits may become well developed in from two to three months. Czerny and Krawkow claim to have produced it in animals in from three to sixty days through the estab- lishment of suppurative processes, caused by inject- ions of turpentine and of staphylococci. Experi- ments made in Ziegler's laboratory throw doubt upon these investigations although they are generally accepted. The administration of the sodium salt of chondroitin-sulphuric acid to animals does not pro- duce amyloid change (Oddi, Kettner, Wells). There is also no evidence that amyloid is formed from dis- integrating red blood-cells. Experimental amyloidi isis has also been produced by injections of gonococci and other bacteria, various bacterial products and many chemical substances. Amyloidosis is not-uncommon in white mice affected with carcinoma or sarcoma, but will not develop in such mice after extirpation of the spleen. Amyloidosis is also said to occur in horses used for the production of antidiphthcritic serum (Pearce and Pease). As a rule, the formation of amyloid takes place very slowly. It occurs most frequently between the tenth and thirtieth years, but may be found in new-born infants (congenital syphilis) , and also in extreme old age. Occurrence. — Amyloid occurs most frequently as a widespread deposit in one or several organs, especi- ally affecting the spleen, liver, kidneys, and lymph glands. Next to these the mucosa of the endocar- dium, stomach and intestine, the adrenals, and the omentum may show a marked degree of the change. In all of the organs it may occur to such an extent that it affects greatly the gross appearance. It is less frequently found in the intima of the great vessels, mucosa of the respiratory and urinary passages, thy- roid, lungs, ovaries, testicles, prostate, bone marrow, salivary glands, and muscle. In these its occurrence is usually so limited that its presence can be made out only by means of the microscope. The degree of the change varies very much in different cases. The kidneys may show a marked deposit while the other organs may contain but little amyloid; in other cases the liver or spleen may be the chief seat of the change. The primary seat of the deposit and the order in which the different organs a re affected vary with the individual case, and bear no definite relation to the associated pathological condition. Local deposits of amyloid occur rarely in single lymph glands following inflammatory processes (mesenteric glands after typhoid), in scars, local inflammations, hyperplastic growths, tumors (osteofibroma of tongue, chondroma of lung), in the tongue, tonsils, larynx, trachea, and bronchi, following syphilitic processes in the wall of the urinary bladder, and in the scars of liver gum ma ta. Klebs obtained the amyloid reactions in a hard chancre. Numerous authors have found amyloid in pathological conditions of the cornea and conjunctiva (trachoma, staphyloma, etc.). It has also been found in old blood clots and thrombi, and frequently in the cartilages of old individuals who have presented none of the pathological conditions with which amyloid is usually associated. Localized amyloid is sometimes found in tumors, usually in endotheliomata. These local deposits of amyloid sometimes form tumor-like masses under conditions in which it is impossible to establish any relationship between them and any other pathological process. The causes and manner of formation of localized amyloid are unknown. There appears to be some relationship between cartilage and elastic tissue and these localized amyloid masses. In the local forma- tions the amyloid is found chiefly around the lymph- vessels, but also in the vessel-walls and tissue-spaces. On the whole these local amyloid deposits must be very rare; and it is probable that hyaline formations have sometimes been mistaken for amyloid. In a wide and varied pathological experience I have never seen any localized deposits of true amyloid. The corpora amylacea found in the prostate, nervous -\ stem, lung, etc., sometimes give a reaction resembl- ing that of amyloid (see Corpora Amylacea). Macroscopical Appearances. — When the de- posit of amyloid is at all extensive, it is readily rec- ognizable by the naked eye; but the degree and nature of the deposit and of the associated degenera- tive conditions vary so much that no general descrip- tion can be given which will apply to all cases. The organ is usually swollen and plumper that normal, its edges are more rounded and its fissures deepened. Its volume and weight are increased, the latter sometimes four- to fivefold. The consistency is greatly increased; in severe cases the organ may have a wooden hardness. There is also a great loss of elasticity, so that pressure indentations made upon the surface of the organ remain for a long time. The blood-content of the" affected organ is usually greatly diminished, so that its color becomes grayish or yellow if much fatty change is present. Very characteristic is the shining, translucent, waxy appearance of the cut surface, resembling that of bacon (lardaceous). The differences in histological structure of the various organs lead to individual appearances when amyloid is present, and these will be described separately. The iodine test is best applied to fresh tissue. A moderately strong LugoPs solution should be used after washing out the blood with dilute acetic acid, as the color resulting from the combination of the red hemoglobin and yellowish-brown iodine very closely resembles the mahogany red of the amyloid. The iodine solution is poured over the freshly cut surface, allowed to stand for a minute or so, and then washed off. The amyloid areas are reddish-brown, the non-amyloid ones yellow. If dilute sulphuric acid is now applied, the amyloid portion may become dark green to black, or dark violet, while the unaffected tissue is of a clear gray color. This gross reaction is plainly seen, as a rule, only when the amyloid deposit is marked; but sometimes, as in the intima of the large arteries, it may be brought out very distinctly when no other appearances point to the pres- ence of amyloid (see Plate VII.). Microscopical Appearances. — Microscopically, amyloid appears as a homogeneous, hyaline substance, of "rather high refraction, which is deposited al- most exclusively in the walls of the capillaries and smaller arterioles and veins. In its earliest stages it appears as a homogeneous layer outside the endothel- ium, but in more advanced cases, owing to the atrophv of the intervening tissue, the masses of amy- loid increase greatly in size and may finally become con- fluent, so that the entire tissue, or a large part of it, may be replaced by amyloid. The amyloid in the tissue-spaces probably lies around the small lym- 304 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES PLATE VI ~»*. ^ Fig. 3. Fig. 1. H Fig. 2. AMYLOID DEGENERATION IN DIFFERENT ORGANS FIG. 1. Section i if an Amyloid Liver, Showing the Effects of stain- ing it Willi aSolutionof Iodine, re. Normal liver tissue; '>. tissue tliat has undergone amyloid degeneration; c, Glisson's capsule magnified 35 diameters. (Ziegler.) Fig. 2.— Amyloid Kidney, stained with Aniline Violet. The amy- loid is stained red. The deposit is most marked in the capillaries of the glomeruli and in the small arteries, and is seen also as a tine hyaline ring surrounding the membrana propria of the tubules. Mag- nified 400 diameters, i Ribbert.) Fig. 3.— Section of an Amyloid Liver After being Treated with Methyl violet and Acetic Acid, a. Elongated masses of liver cells ; 6, amyloid substance: i\ endothelium of the capillaries; e, colorless blood corpuscles. Magnified 150 diameters. (Ziegler.) Fig. 4. — Amyloid Degeneration of the Follicles and Pulp of the Spleen. (Alcohol; methyl violet; hydrochloric acid.) «. Follicular tissue in a marked state of amyloid degeneration; o. pulp tissue in which the degeneration has begun. Magnified 300 diameters. (Ziegler.) i: i ; i 1 : i : 1 x < i : handbook ok tiii: medical SCIENCES Amyloid phatics. In severe grades of amyloid formation the fibers of the connective-tissue reticulum and the base- menl membranes of the glands may give an amyloid reaction so that the entire organ or tissue may appear tn have undergone an amyloid transformation. In this way large nodules or tumor-like masses are formed. I' must be emphasized, however, that inits earliest stages the first appearance of amyloid is rys next to endothelium. [t is never deposited in living cells. The tissue Cells proper take no active put in the process, and the cnanges found in these cells are to be regarded as secondary. The lumen of the affected vessel is ,,.„ narrowed by the increasing deposit, and the ilting disturbance of blood supply leads to degen- ve changes (atrophy and fatty degeneration) of the cells of the affected region. Pressure-atrophy is commonly found in the amyloid liver, while el lv swelling anil fatty degeneration arc more common in unyloid kidney. The deposit of amyloid between ami around the cells near the blood-vessels leads to similar changes. The individual vessels are not. illy affected throughout, and different vessels of the same organ may show the change in very different degrees. The microscopical appearance of amyloid in sec- tions stained with hematoxylin and eosin is so similar to that of hyalin that a differential diagnosis be- tween the two deposits can be made only by means of e specific staining reaction. Of these the be I and most practical is the Van Gieson method. The sections are overstained in hematoxylin and then stained for one-half to one minute in a concentrated water solution of picric acid to which enough of a concentrated water solution of acid fuchsin has been added to give it a distinctly red color. By this met hod amyloid is stained a pinkish-brown or yellow, while hyalin takes a deep red color. The iodine reaction does not show so well in hard- ened material, so is best applied to fresh tissue. The specific reactions of amyloid with various aniline dyes are classic in the history of microchemistry, and it is largely to the wonderful amount of interest be- stowed upon these that this branch of pathological technique owes a very great part of its development. The aniline stains most commonly used are methyl and gentian violet, methyl green, thionin, toluidin-blue, kresyl-echt-violett, and iodine green. The amyloid tissue is best hardened in alcohol or formol and cut without embedding or upon the freezing microtome after washing out the alcohol. The sections are then stained for five to ten minutes in a two to five per cent, solution of the stain, differentiated with dilute acetic acid, and mounted in glycerin or syrup. With all of these stains amyloid exhibits a metachro- masia. Methyl and gentian violet, kresyl-echt-violett, ami iodine green stain the amyloid portion ruby red, while the non-amyloid is stained blue. Methyl green stains the amyloid a sky-blue, the non-amyloid tissue a bright green. Thionin, toluidin-blue, polychrome- methylene blue and other metachromatic dyes are used to give similar reactions with amyloid, but are not as satisfactory, as kresyl-echt-violett which is best used in a five per cent, carbolic acid solution. The best metachromatic stains are secured by fixing in formol for twenty-four hours, sectioning on a ing microtome, staining, and examining in water. The metachromatic reactions are not satisfactory with celloidin sections but good results can be ob- tained, with paraffin sections. Amyloid may also be stained with scharlach R and Sudan III, but the Its are not satisfactory. The reactions with the fat-dyes are due to the presence of lipoids in the amyloid tissue. None of the metachromatic reac- tions is permanent; the sections so treated gradually fade. On the whole, the Van Gieson method, which can be applied to either paraffin or celloidin sections, is the most convenient and practical stain for Vol. I.— 20 the differentiation of amyloid, since it differentiates connective-tissue hyalin by staining it deep red; and epithelial hyalin which stains like amyloid with this stain is differentiated by its different tissue- relations. The variability in staining of amyloid may be dependent upon differences of composition as well as of density. The met hyl-violet reaction appears to depend upon the albuminous constituents, while the iodine reaction depends upon unknown substances that can in various ways be removed from the amyloid. Liecr. — This organ is very frequently I he seat of amyloid deposit. Outside the endothelium oi the liver capillaries, between it and the liver cells, t here is deposited a layer of amyloid, which, as it increases in thickness, presses upon the liver cells and separates them from their normal relations with the blood, SO that (hey undergo atrophy and degeneration, and finally may entirely disappear. The amyloid masses thus become confluent, the capillary walls are pressed together, and the only cells left in the area are the endothelial cells, which may persist for a long time. The intermediate zone of the lobule is almost always affected to a greater extent than either the central or the peripheral one. The walls of the larger blood- vessels may also show the deposit. In more advanced cases the entire lobule may be replaced by amyloid. This marked change is usually confined to single scattered lobules, so that these appear to the naked eye as grains of boiled sago (sago-liver). More rarely the greater part of the liver may be replaced by con- fluent masses of amyloid, whereby the organ acquires a wooden hardness and on section resembles the translucent portions of bacon (S peck-leber) . Spleen. — In the spleen the amyloid deposit takes place in the fine reticulum of the pulp beneath the endothelium of the blood spaces. The follicles may alone be affected, appearing enlarged and translucent like boiled sago (sago spleen); or the chief deposit may be throughout the pulp, or may involve both pulp and follicles (Speckmilz, Schinkenmilz, lardace- ous spleen). The arterioles of the follicles are often the only portions of the organ which show the deposit, and it is in these that the earliest appearance of amyloid in the body as a rule occurs. The lymphoid cells disappear, and the spleen may ultimately con- sist only of an amyloid network between and around the blood spaces, the endothelium of which may be preserved. Kidney. — The afferent arterioles of the glomeruli are usually first affected, then the glomerular capil- laries and efferent vessels, and finally the smaller vessels throughout the entire organ. The change is never so marked in the medullary pyramids as in the cortex, but it may appear early in the straight vessels of the former. As the disease advances the deposit extends from the intertubular capillaries to the basement membrane of the tubules, which may ap- pear as if surrounded by a hyaline ring. The intinia of the larger branches of the renal artery may show small and irregularly scattered deposits. Since the glomeruli are the chief seat of the deposit, they appear on the freshly cut surface of the organ as small, firm, translucent dots usually about the size of pin- heads. Marked fatty degeneration and cloudy swelling of the renal epithelium are always present, and the kidney presents the microscopic picture of a chronic parenchymatous nephritis, more rarely that of a chronic interstitial process. Lymph Glands. — Extensive amyloid deposit is not common in the lymph glands, but scattered masses are very frequently found in them; and the walls of their small arterioles usually show a. moderate degree of change in all cases in which the liver, spleen, and kidneys are extensively affected. Local inflamma- tory changes, both of the lymph glands and the tonsils, are frequently accompanied by the formation of small masses of amyloid in connection with hyaline 305 Amyloid REFERENCE HANDBOOK OF THE MEDICAL SCIENCES deposit, and the close relation of these substances is nowhere else so well shown as in these organs. In advanced cases the deposit may extend from the neighborhood of the capillaries into the reticulum, causing atrophy of the lymphadenoid cells. Muscle, Fat Tissue, etc. — In striated muscle amy- loid deposit is rarely found. It has been found in the tongue and in the muscles of the larynx in the shape of nodular masses. The deposit takes place first in the walls of the capillaries of the endomysium, and as it increases in size the sarcolemma comes to be sur- rounded by a clear, hyaline mass. As the muscle fiber is thus separated from its blood-supply it under- goes atrophy and degeneration, finally disappearing, so that the deposits of amyloid become confluent into nodular masses. A similar process may take place in heart muscle and in unstriped muscle, but is of rare occurrence. The amyloid deposits in striped muscle occur very frequently in the scars of gum- mata, but occasionally no evidences of preceding pathological changes can be made out. Adipose tissue is often extensively affected by amyloid disease, the deposit taking place in the walls of the larger blood-vessels and of the intercellular capillaries, so that the fat cells come to be surrounded by a thin hyaline layer. Heart. — Amyloid degeneration of the endocardium, particularly in the right auricle, is not rare. I If rarer occurrence is the formation of amyloid in the myocardium. Adrenals. — In this organ the cortex is usually the seat of amyloid change. As the amyloid is formed between the capillary wall and the epithelial cords the latter undergo atrophy and may in part disappear. Mucous Membranes. — The mucous membranes of the respiratory tract are very rarely affected. Scat- tered deposits may occur in the mucosa of the stomach and intestine, producing more or less ex- tensive thickenings of the mucosa, which show the characteristic homogeneous, glassy appearance of amyloid. Large elevations may undergo ulceration, and at the bottom of the ulcer remains of the amyloid may be preserved. The large intestine is more frequently affected than the small. The deposit is in the walls of the capillaries of the mucosa and sub- mucosa, particularly in those of the villi; amyloid deposits also occur in the intestinal muscularis. Only in very rare cases is amyloid found in the mucosa of the genito-urinary tract. General Nature op Amyloid Disease. — As stated above, the formation of amyloid is almost always secondary to other processes which are ulcerative or inflammatory in character, and of in- fective nature. While not in itself a true degenera- tion of ceil protoplasm, the process is essentially degenerative in character, in that it leads to marked disturbances of nutrition. The deposit in the walls of the blood-vessels leads to partial or complete ob- literation of their lumina, thus producing permanent interference with the circulation. As a result of this disturbance of nutrition, atrophy, fatty degeneration, or necrosis of the tissue cells takes place. The pres- sure of the amyloid deposits between the cells leads to similar results. Fatty degeneration and infiltration are almost always present to a greater or less degree in amyloid disease, and to a certain extent must be regarded as coincident processes produced, perhaps, by the same general disturbances of metabolism which give rise to amyloid. Severe anaemia is usually associated with the condition, and death takes place as a rule from a gradually increasing marasmus. The presence of the amyloid in the tissues does not usually set up any local reactive process. Only rarely (usually in local amyloid formations) does the amyloid act as a foreign body and give rise to the formation of foreign-body giant cells that may exert a phagocytic action upon fragments of amyloid. The formation of such phagocytic foreign-body giant cells has been observed in the experimental amyloidosis of rabbits. Symptoms. — The marked alterations in the struc- ture of the affected organs and tissues lead to func- tional disturbances, which, however, may be very slight when compared to the extent of the deposit. The general clinical picture of the condition will vary, of course, with the organ affected and with the extent of the disease, so that a comprehensive description is not possible. Moreover, from the nature of the case, it is manifestly difficult or impossible to separate the symptoms of amyloid deposit from those of the dis- ease leading to or associated with it. The nature of the primary process will modify very much the clinical appearances dependent upon the amyloid change. Frequently the beginning of the condition is shown by a rapid increase in the marasmus already exis- ting, and by the enlargement of liver and spleen. These phenomena are always more marked in syphilis and in chronic ulcerative processes than in pulmonary tuberculosis. In such conditions as chronic varicose ulcers of several years' standing a rapid increase of the cachexia is usually pathognomonic of amyloid disea Associated with enlargement of the liver certain disturbances of digestion go hand-in-hand: absence of bile-pigment in the feces, fecal decomposition, meteorism, etc. Icterus is rarely present, and ascites only as associated with a general hydremic or cachectic- anemia. Marked amyloid deposit in the kidneys is not always known by disturbances of its function. The urine may show no changes; but as a rule al- bumin is present, the amount is increased, and the sediment contains hyaline casts, though usually not in great numbers. The latter never give the amyloid reaction, in spite of the repeated statements that they do. As amyloid deposit in the kidneys is, in the majority of cases, associated with chronic inflamma- tory changes, the character of the urine may vary greatly. Usually the picture is that of a chronic parenchymatous nephritis. Marked amyloid dis- ease of the intestine is usually accompanied by foul diarrhea. Diagnosis. — The nature of the primary affection must first be considered. If in patients affected with any one of the chronic diseases known to be associated with amyloid (chronic tuberculosis, syphi- lis, chronic suppurative processes), painless swellings of the liver and spleen arise, in association with albu- minuria and extreme paleness of the skin and mucous membranes, the diagnosis of amyloid is made very probable, but in early stages of the disease the diagnosis is difficult. Duration. — The earliest stages of amyloid change cannot be ascertained clinically. It is probable that in many cases the process develops through several, or even many years, with alternate periods of improve- ment and exacerbation. It may, however, develop within shorter periods, as in a case observed by Cohnheim, in which suppuration of bone after a frac- ture led to well-developed amyloid disease within a few months. The duration of well-marked cases de- pends upon the organ chiefly affected. Extensive changes in the kidney are much more serious than those of the liver or spleen, as they may lead to .death within a few weeks or months. Prognosis. — This is in general unfavorable. It is probable that amyloid, when once formed, is not removed from the site of deposit. In all cases in which the condition is so marked that the diagnosis is certain, death usually occurs within short periods. Temporary improvement may take place; and in some cases, especially after operation for chronic purulent conditions of bone, the disease apparently comes to a standstill, marked general improvement takes place, 306 REFERENCE EANDBOOK OF THE MEDICAL SCIENCES Amylum the liver swelling decreases, and the albuminuria dis- appears It is, of course, impossible to say to what extent these symptoms were due to the amyloid A similar improvement has been - the jl ,,,' a prolonged inunction cure in a case of amy- loid associated with syphilis so that the | is in syphilitic amyloid is usually regarded as more favor- able. Corneal tumors may slowly disappear under the influence of local irritation and inflammation. Treatment. — For the well-established condition it is hardly probable that treatment will avail, though iodine, ammonium chloride, potassium iodide, dilute nitric acid, etc., have been recommended. When syphilis is present tin- treatment should be anti- syphilitic. The improvement of the local or general primary condition is, of course, the most important therapeutic line to be followed: and in connection with this the general improvement of nutrition. Of far , r importance are prophylactic measures, even to the extent of such radical procedures as amputation in cases of chronic varicose ulcerations, chronic suppuration of bone-, etc., in which persistent opera- tive and therapeutic measures have been without result. General amyloid disease is much less common than it was fifteen years ago, and this change is to be ascribed to the greater tendency to surgical operations, and the greater success attending the preventive treat- ment of suppurative processes. Even in the case of inic pulmonary tuberculosis modern methods of treatment seem to have lessened the occurrence of amyloid. Aldeed Scott \Yarthin-. Amvlopsin. — See Pancreas. Anatomy and Physiology of the.' Amylum. — Starch. Corn starch. The starch grains* separated from the fruit of Zea mays Linn£ u. Graminea), i V . S. P.). There appears to be no ial reason why the Pharmacopoeia should thus restrict its requirements to corn-starch, except that this variety is cheap and abundant and readil3 r defined Fig. 1S4. — Section of Seed of Vetch. Vicia salira Linn, showing rounded granules of starch in ceils otherwise filled with granular nitrogenous substance. X 190. and described. Our account of starch, therefore, will apply to the entire class, and will be followed by the differential characters of the more important varieties. Starch is the ordinary form of reserve carbohydrate nutriment in plants, at least in most of those of the higher classes, and in many of those of the lower classes. It may be reserved for but a brief period, at the point where it is produced, or it may, after pro- duction, be changed into diffusible forms and trans- ported to special storage reservoirs, where it is again transformed into starch, and may remain for months or even for years. For example, being produced only under the influence of light, it may be consumed dur- ing the succeeding hours of darkness, or, upon the ; hand, it may l>e transported to the bulb or tuber of a desert plant, which may exist dormant ii sand for several years, consuming this starch supply upon the recurrence of a period of activity. In the most highly developed and largest family of plants, . and in some others, inulin, a rel ' I compound, altogether replaces starch as a reserve food. Th of starch present in vegetable tissues is often very great, being about seventy per J Si Fig. 185. — Wheal Starch. Fie. 1S6. — Maize Starch. cent, in dried potato, and about the same in corn meal and wheat flour. With the exception of some rare cases in which special forms are found, starch occurs in peculiar grains, which are free in the cell cavity. It originates in a small colorless body known as the amylogenic body, upon which the starch gathers in layers, the central body becoming the nucleus, and being located in the grain at the hilum. The numer- ous layers of the grain are discernible under the micro- scope by their different degrees of refraction, due apparently to different amounts of water, as they disappear under the effect of drying heat. The grains may exist singly, or coherent in masses containing a variable number. The limits of this numerical varia- tion are often fairly constant in a given plant, and Fig. 1S7. — Potato Starch. may thus be utilized as a characteristic. This cohe- sion often produces peculiar forms of the grains, which forms also become characteristic. Even if this is not the case, the form of the grains in a given plant is usually characteristic, as is the position of the hilum. The larger grains usually become ruptured or fissured at the hilum. This fissure may be simple or in various ways compound, and the forms so result- ing are also characteristic. In all starches in the living plant there must be small grains of various sizes in process of formation, but the largest of them usually fall fairly well within certain limits, so that the extreme limits of a given variety are of diagnostic value. Although single starch grains are colorless and semitransparent. masses of them are pure white. Starch powder is very fine and smooth, but the ulti- mate grains are hard and gritty. They are very hygroscopic. 307 Am.\ linn REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 188.— A Granule of Potato Starch Swollen by Boiling. Starch has no odor, but a peculiar, though slight, farinaceous taste. The grain consists of two sub- stances, granulose, which is colored blue by iodine, and another substance very similar to cellulose, colored pale yellow by iodine. Starch is insoluble in water and alcohol. Several substances are often spoken of as solvents of starch, but they all apparently change it into some other com- pound before the solution takes place. Water, under the influ- ence of heat, converts it into hydrated starch, a transparent, jelly-like mass, which is then soluble in water. Alkali hy- drates of a strength of more than five per cent, similarly dissolve it. Both these solu- tions are then precipitated by lime water, lead acetate, tan- nin, and some other reagents. Diastase, the principal enzyme which naturally exists with starch, is the agent which in the plant converts it into sugar, suitable for imme- diate use as food. The same agent can be made to perform this office artificially, as can dilute acids under the influence of heat, and as is done by the natural processes of digestion within the animal body. From the above-mentioned characters of starch, it is seen that it can readily be obtained by grinding finely any cellular structure which contains it, washing out with cold water and filtering or allowing to settle. It is also seen that, be- sides the interest which centers in starch for its own value, the character- istics of the starches contained in different plants, and more especially in drugs, may be utilized in the identification of the latter, in powdered form, as well as in the detection of adulterations. Fig. 189. — Arrowroot Starch. Varieties. — The only certain means of determining from what source a given specimen of starch has been derived is to examine it microscopically, when the size, shape, markings, and other visible peculiarities of the granules will generally suffice to make it cer- tain. The accompany- ing illustrations of the commoner kinds are magnified uniformly 350 diameters. 1. Wheat Starch, from various species and varieties of Triticum L. (fam. Graminea ) (Fig. 185). In irreg- ular, angular masses, which are easily re- duced to powder; under the microscope appear- ing as granules, mostly very minute, more or less lenticular in form, and indistinctly concentrically striated. The granules average about 0.050 milli- meter in diameter. 2. Maize, or Corn Starch (defined above, Fig. 186), i- smaller than the preceding, about 0.030 millimeter in diameter, of polyhedral form, with central hilum. 3. Rice Starch, from Oryza saliva L. (fam. Gram- 308 Fig. 190. -Sa K o. ineee) resembles maize starch, but is very much smaller. 4. Potato Starch, from Solanum tuberosum L. (fam. Solanacecr), (Fig. 1S7) consists of two classes of granules mingled together — fine spherical ours, from 0.01 to 0.03 millimeter in diameter, and large ovoid ones with very eccentric hilums and very distinct ruga-, recalling oyster or clam shells, from 0.14 to 0.18 millimeter long. 5. Arrow-root, from Maranta arundinacea L. (fam. Marautacew) (Fig. 1S9) is finer than potato starch, which it somewhat resembles; the granules are more spherical, with blunter, thicker ends, very distinct eccentric fissures, and less distinct ruga. Canna Fig. 192.— Oat Starch. starchy a variety of arrow-root, has enormous granules, nearly twice as large as those of potato. Neither of these varieties has the small forms of that from potato. 6. Sago, chiefly from several species of Metroxylon Rottb. (fam. Sabalacea?) (Fig. 190) has medium-sized (0.04-0.07 mm.), oblong, rather irregular, often faceted, sometimes shoe-shaped granules, with eccen- tric hilum and fairly distinct ruga. The sago of com- merce is often half-cooked, with many of the granules destroyed, and is still more often merely tapioca. 7. Tapioca (Fig. 191) has spherical, medium-sized granules, with large facets; commercial tapioca is also partly cooked. (See also separate article on Tapioca). Besides the above are the starches of numerous familiar grains and roots, which are not separated for sale or use, but which are of interest in detecting adulterations, mixtures, etc., or in identifying the powders of drugs. The accompanying cuts of oat and turmeric starches will serve as illustrations of this large class. Fig. 193.— Turmeric Starch. Medical and Surgical, Uses of Starch. — This sub- stance can in no sense be called a medicine, :i - it is abso- lutely without physiological action. It is the type of crude carbonaceous or non-nitrogenous food, and its conversion into sugar in the mouth, stomach, and intes- tine is one of the elementary facts of digestive physi- ology. Asa toilet powder the finer varieties — rice and corn starches — are in universal use, and one or other of these is the foundation of most of the proprietary powders. Boiled starch, and especially the flours of starchy substances, are frequently used as poultices, but they REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anuphrurilslacs arc mil so convenient and suitable as the mucilaginous of linseed and slippery elm. Starch mucilage is occasionally used for immovable bandages, but it is less adhesive and less suitable for ibis purpose than flour paste, glue, dextrin, silicate of potash, or plaster of Paris. One part dissolved glue, as prepared for cabinet-makers' use, and two or three parts starch mucilage, a little thinner than the laun- dress uses it, mixed and applied hot, make a most , Unit ( ibination for such bandages — light, very and agreeable in color. The only official preparation of starch is the Glycer- Glyceritum Amyli, ten parts of starch dissolved in ■i v of hoi glycerin). This is a permanent trans- lucent jelly, useful in moistening pill masses, for emulsions and similar purposes. Iodized Starch i/kiii I odd I ii in), formerly official, is rather a prepa- ration of iodine. It is made by triturating five parts of iodine with ninety-five of starch, with the aid of a lit- tle water. It is a blue-black powder, and a suitable preparation to administer for free iodine if it is desired to give that drug internally. Henry II. Rusby. Amyotonia Congenita. — This disorder was first described by Oppenheim in 1900, under the term \1\ iinnia Congenita. It was later called Amyotonia i ongenita by Collier and Wilson, since the name myotonia congenita, or Thompson's disease could so readily be confused with myatonia congenita or i tppenheim's disease. It has been termed congenital muscular atony by French writers. It is a condition illy found in children, in which there is extreme flaccidity of the muscles associated with the entire loss of the deep reflexes, most marked as a rule at birth, and tending to slow but gradual amelioration. The muscles are weak, but are apparently not para- lyzed. In a paper which appeared in 1904, Oppenheim published more in detail concerning the condition, lie says that he had observed for some years children of from several months to two years whose muscles, chiefly those of the lower extremities are immobile and flaccid. Objectively there is marked hypotonus, almost atony, with loss of the reflexes. The flaccidity is so marked at times that the limbs can be placed in almost any position. The motility is always diminished, varying considerably according to the patient. In severe grades the motility is almost nil. In the milder cases certain groups of muscles may ontracted, but feebly. In very light involvement the hypotonus is marked, and the patients lack force in their muscular movements. In the majority of instances the lower extremities are involved, but in a few, other muscles are involved. Thus far, the eyes, tongue, pharynx, and diaphragm seem to be spared. The intercostals have been known to be affected. On palpation, the muscles are soft and flabby, are thin, but not apparently atrophied. Electrical excitability is usually markedly diminished, at times lost, again only slightly involved. The intelligence is apparently uninvolved, as is also the sensibility. It is apparently a congenital affair. There is a tendency to progressive amelioration. The disorder simulates infantile poliomyelitis, but has nothing in common with it. It is a disease of the muscles. This was Oppenheim's disease as he left it in 190-1. Batten, Collier and Wilson, Spiller, Orbison, Skoog, Comby, Haberman, and Maserey have written upon it, and Chene published a small thesis upon the disease in 1910, reporting forty-three cases. Marburg gave a small study in 1911. Spiller was the first to report upon the pathology in 1905. The general tendency has been to regard the dis- order in the light of a dystrophy; most of the authors have said that poliomyelitis could be excluded. Marburg, on the other hand, claims, and with con- siderable evidence, that amyotonia congenita of Oppenheim is a fetal poliomyelitis. Smith Eli Jelliffe. Anabolism.— See V, tula lism. Anacarcliacea.\ — Terebinthinaeea . (The< 'ashew fam- ily.) A remarkable and important family of some fifty-nine genera, chiefly tropical or subtropical, ex- ceedingly vaired in the nature of its products. The mango, the cashew, and the spondias or hog-plum, are important fruits; those of Pistacia furnish a well- known flavoring agent, while the bark of another species yields the commercial resin mastic; the milk juice of several Japanese species of Rhus furnishes Japanese lacquer, and the leaves and fruits of other species Of this genus yield tanning agents. The oil which abounds in several species Of Rhus I more prop- erly called Toxicodendron), and in some other genera, acts as a powerful cutaneous poison. (See Poisonous PI, nils.) II. II. RtJSBY. Anaemia. — See Anemia. Anaesthesia. — See Anesthesia. Anaesthol. — This is an anesthetic introduced by Willy Meyer of New York to replace the A.C.E. mixture. He mixes chloroform and ether in molecu- lar proportions, i.e. 43.25 per cent, of chloroform and 56.75 per cent, of ether by volume, and calls the mixture "M. S." Of this he takes eighty-three volumes, and adds seventeen volumes of ethyl chloride. The mixture has a boiling point of 40° C. { 104° F.), and would seem to be open to the objection urged against the A.C.E. mixture, that constituents of different volatilities do not volatilize equally. We might expect the ethyl chloride to vaporize more rapidly than the ether, and this more rapidly than the chloroform. The experience of anesthetists is that the action of the mixture is little if any differ- ent from that of pure chloroform, and that the amount required is about twice that of chloroform. In other words, the quantities of ether and ethyl chloride are too small to have much effect. The dangers are those of chloroform. W. A. Bastedo. Analeptics. — This term was formerly used to include several classes of agents which were employed to re- store the body to health, after a period of sickness. They were also called restoratives, and included hy- giene, rest, food, warmth, stimulants, and tonics. R. J. E. S. Analgesics. — See Anodynes. Anaphrodisiacs. — These are agents which are used to lessen an immoderate or morbid sexual desire. In the usual and narrow acceptation of the term it includes only the medicinal and physical remedies, but "in a wider sense it embraces as well all the moral, dietetic, hygienic, and surgical measures hav- ing this end in view. The causes of aphrodisia are many, and not the least important is reflex irritation of the genitalia, resulting from physical peculiarities or deformities, phimosis, stricture of the urethra, dis- ease of the prostate, chronic constipation, hemor- rhoids, eczema or fissures of the anus, highly concen- trated urine, etc. In other cases the reflex irritation may be caused by the presence of worms in the rectum, or in the vagina in the case of female children, and by friction of the thighs produced by horseback riding, bicycling, running the sewing-machine, etc. These conditions will each call for its own special treatment in addition to the general measures which should be 309 Anaphrodisiacs REFERENCE HANDBOOK OF THE MEDICAL SCIENCES adopted; for the detection and relief of the exciting cause are difficult problems and far more important than the exhibition of drugs. For another class of patients, those suffering from diseases of the nervous system or those with psychical perversion, psycho- therapeutic measures are of special value. The principal anaphrodisiac drugs are the bromides, camphor, hops, salicin, potassium iodide, coniuni. and chloral and other hypnotics. When there is excessive acidity of the urine, potassium acetate may be of service indirectly in removing this source of irritation. In general, for the treatment of habitual sexual erethism nothing will be found better than physical and particularly mental work to the point of fatigue. The latter accomplishes its results in two ways: first, by exhausting the brain where the sexual impulse (if not reflex) has its origin; and secondly, by so absorbing the patient's interest as to preclude the occupation of his mind by lascivious thoughts. In the general management of a case the physician should advise a non-sedentary life, as much as possible in the open air, light diet, with an absence of meats, coffee, highly seasoned foods, and alcoholic stimulants; the kidneys should be kept well flushed, the bowels well open, and the patient should sleep on a hair mattress, with light covering, in a cool, well-ventilated room. As a full bladder is frequently a cause of irritation, U should be emptied upon going to bed and the first thing in the morning. The patient should arise early and take a cold douche or sponge bath. Charles Adams Holder. Anaphylaxis. — The term anaphylaxis (from &m. up, away, and v\ai, guard, or 0i/Xa|«, protection! also called hypersusceptibility, supersensitiveness, allergy, is a condition of unusual or exaggerated sen- sitiveness of an organism to foreign proteins; in other words, an altered power of reaction toward such pro- teins. Anaphylaxis may be congenital or acquired, local or general; it is specific in nature. Hypersus- ceptibility to any strange protein in itself quite non- poisonous may be readily induced in certain animals by the introduction of a minute quantity of that par- ticular protein into the body. The word anaphylaxis was coined by Richet in 1902 to suggest the opposite condition to prophylaxis, or protection, since it appeared that in certain cases the second injection of a poisonous substance instead of reinforcing the immunity induced by the first, iter susceptibility, so that less than a minimal lethal dose of it caused death. But more recent investigations have shown that the contradic- tion between immunity and anaphylaxis is only apparent, that they have to do with the same general mechanism of the animal body and that in fact the former may be dependent on the latter. For this reason von Pirquet has suggested the word '"allergy (fi/./os, different, and ep)-sta, reactivity) to indicate an altered power of reaction of the body toward a foreign substance, thus combining in the same term a conception of acquired immunity and the related state of acquired hypersusceptibility. Historical. — The first to note and record accurately his observation on this altered power of reaction of the human body was probably Jenner, who at the end of the eighteenth century in England began to study the modification of the form of smallpox by previous vaccination, and noted particularly the immediate reaction to variolous matter by the skin of persons who had had either smallpox or cowpox. This we now recognize as an anaphylactic phenome- non of great importance, as we shall show later. Early in the last century (1839) Magendie found that rabbits which had tolerated two intravenous injections of egg albumin without any ill effects immediately succumbed to a further injection made after a number of days. Later, workers attempting to obtain precipitins frequently found that some of their animals died suddenly during the course of treat- ment from no apparent cause, though we now know they were in a state of anaphylaxis to the foreign protein. Other analogous instances may be found scattered throughout the literature, the true import of which was not realized until 1905. Von Behring and Kitashima (1901) reported an increasing sensitiveness on the part of guinea-pigs to successive small doses of diphtheria and tetanus toxins. This they called the paradoxical phenomenon or "hypersusceptibility'' (the first use of this term in a specific sense). This hypersensitiveness to toxil - is not true anaphylaxis, which is produced by prot which are non-poisonous in themselves and, as Hektoen has recently pointed out, the animal dies with the symptoms of the disease in question and nut those of anaphylaxis, which are constant for the same species of animal. Furthermore, the "hypersuscepti- bility" described by von Behring seems incapable of passive transmission to normal animals, though anaphylactic hypersensitiveness is thus transferable. Portier and Richet (1902) found that if dogs were given a small dose of a glycerin extract from the tentacles of actinia, and then in fifteen or twenty days given a second small dose, the animals quickly succumbed. The dose given was so small as to cause no symptoms in a normal animal. They were the first to use the word "anaphylaxis" to indi hypersensitiveness to a poison, which they interpreted as the opposite of prophylaxis. Arthus (1903) was the first to experiment with a non-poisonous substance, and at the instigation of Richet, studied the effect of repeated subcutaneous injections of sterile normal horse serum in rabbits. These caused a local reaction, even a necrosis, about the site of injection which is called the "Arthua phenomenon," and is now interpreted as a local anaphylaxis. At about this time Theobald Smith began to be puzzled at the sudden and unexplained death of guinea-pigs used in the standardizing and subsequent testing of diphtheria antitoxin, while von Pirquet, approaching the same subject from an entirely different angle, was noting clinically the peculiar reactions of the human bod}- to serum therapy in diphtheria. The fact that guinea-pigs which had been used for the testing of diphtheria antitoxin frequently died when later given an injection of serum had been noticed in several laboratories soon after the discovery of diphtheria antitoxin, but no one seems to have perceived any connection between the two injections until this time. Most of the workers with serum regarded it as an accident pure and simple or that the animal's vital resistance had been lowered by the first treatment; some even thought that it was the effect of cold, as the serums were usually kept in the ice chest and were injected at once after removal from the ice box. During Ehrlich's visit to America, however, in 1904, 1 bald Smith told him the fact that guinea-pigs often died suddenly when used a second time as described above, and upon Ehrlich's return he gave the problem to Otto, at that time his assistant. Otto began to publish the results of his work the next year, describ- ing acute anaphylactic shock under the name of "Theobald Smith's phenomenon." Meanwhile, the clinical studies of von Pirquet and Schick bore fruit in their classic monograph on " the serum disease" (1905). which described in detail the syndrome that often follows injections of horse serum in man. They noted an "altered reaction" of the human body to repeated injections of serum, pointing out its profound bearing on the meaning of the in- cubation period of disease; they drew original and far-reaching conclusions concerning the relation of these clinical observations to hypersusceptibility, 310 • REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anaphylaxis and they called al tention to the tuberculin rea< an analogous instance <>f anaphylactic sensitivi In moo and liiini. ll.i-i-nau and Anderson simul- eously with Otto took up a systematic study of anaphylaxis. They bad also encountered the phe- nomenon described by Theobald Smith to Ehrlich, and it occurred to them thai there might be some relation between it and certain exceptional instances of ; iath following the injection of horse serum in man. Otto, whose "paper appeared first (1905 described the typical anaphylactic reaction of the . ig to a second injection of horse serum; be onstrated that the diphtheria poisons play no part in the reaction, and later worked out many of the ntial features of the phenomenon, notably the "refractory" period and the passive transference of the anaphylactic state to normal animals by means of the serum of sensitized animals (19i)7). Kosenau and lerson, working also mainly with horse serum and ea-pigs, established in a series of researches ex- ling over several years (1905—1909) many of the facts of experimental anaphylaxis, notably the itieity of the reaction and the nature of anaphylac- tic substances, the maternal transmission, the relation to endotoxins, and immunity, etc. Noteworthy contributions to the study of this interesting subject have been made in ever increasing volume in recent years. The chemistry of the itizing substances has been investigated by Vaughan and Wheeler, and Wells; the physiology and pathology of the anaphylactic state by 7 Gay, Southard, Besredka, Auer and Lewis, and Schultz and Jordan. The important subject of anaphylaxis in relation to bacterial proteins is still in the con- troversial stage, and active researches have been carried out by Friedberger and his assistants, Doerr, lemann, Rosenow, Cole, and others, and finally the important bearing of anaphylaxis upon clinical and forensic medicine has been demonstrated by von Pirquet, Uhlenhuth, Thomsen, Pfeiffer, and others. Serum Anaphylaxis. — Horse serum, either normal or antitoxic, when injected into normal guinea-pigs, causes no symptoms. By "normal" guinea-pigs is meant animals that have not previously received treatment of any kind and were born of untreated mothers. As much as 20 c.c. may be injected into the peritoneal cavity of a guinea-pig without causing any apparent inconvenience to the animal. When injected subcutaneously there may be a slight traumatic local reaction, which disappears in a few hours. Small amounts of horse serum, such as 0.25 c.c. may be injected directly into the brain without causing any untoward symptoms. Very characteristic symptoms, however, are pro- duced by horse serum when injected into a susceptible guinea-pig, i.e. one that has received a prior injection of horse serum. The symptoms are apparently 7 the " whether the injection is made subcutaneously or into the peritoneal cavity, or whether normal or antitoxic horse serum is used. In five or ten minutes after injection the pig manifests indications of respi- ratory embarrassment by scratching at the mouth, coughing, and sometimes by spasmodic, rapid, or irregular breathing; the pig becomes restless and agitated; there is a discharge of urine and feces. This stage of exhilaration is soon followed by one of paresis or complete paralysis with arrest of breathing. The pig is unable to stand or, if it attempts to move, falls upon its side; when taken up it is limp. Spas- modic, jerky 7 , and convulsive movements now super- vene. This chain of sy 7 mptoms is very character- istic, although not always following in the order given. Pigs in the stage of complete paralysis may fully recover, but usually convulsions appear, and are almost invariably a forerunner of death. Symp- toms appear about ten minutes after the injection has been given; occasionally in pigs not very sus- ceptible they are delayed thirty to forty-five minutes. Only in one or two instances of tic- many bund observed by Rosenau and Anderson bave the symptoms developed after on.- hour. Piga developing symptoms as late as this are not very susceptible ami do not die. Death usually occurs within an hour and frequently in less than thirty minutes. If the second injection be made directly into the brain or circulation, the symptoms are manifested with explo- the animal frequently dying within two or three minute . A tall in temperature occurs which in fatal cases may be as great as 13° C. (Pfeiffer). Owing to apparent relation betv a the depression in ten ature ami the severity of the symptoms, the extent duration of the fall have beet degree of anaphylaxis. Very minute reinjeetions of antigen, however, have 1 n known to raise the temperature. The blood during anaphylactic shock shows a leucopenia, and a diminution in complement. Immediate autopsy shows a striking condition of the lungs described by Gay and Southard, also by Auer and Lewis. When the chest is opened the lungs do not collapse but remain fully and permanently dis- tended, forming a cast of the pleural cavities. The heart continues to beat strongly for some time. Asphyxia, due to inspiratory immobilization of tic- lungs, is therefore probably the immediate cause of death. The essential features, then, of experimental anaphydaxis are: (1) the first injection, consisting of a bland alien protein, non-poisonous in itself, which sensitizes the animal; (2) an interval of about eight to fourteen days; (3) the second injection of the same protein which produces a reaction known as acute anaphylactic shock. Judged by the severity of the symptoms of the acute anaphylactic reaction the guinea-pig is appa- rently the most susceptible of animals (being 400 times more sensitive than the rabbit, according to Doerr), but probably all animals may be sensitized to a greater or lesser degree, although our methods of observation are still too crude to admit of any accu- rately graded comparison. White mice were long thought to be incapable of anaphylaxis, probably because of the absence of sudden death from as- phyxia, so constant and striking in the guinea-pig; but Schultz and Jordan have shown that white mice do react toward horse serum with restlessness, marked irritability 7 of the skin, passage of urine and feces, and temperature and blood-pressure changes. In dogs (according to Richet, who worked with them almost exclusively 7 ) the principal symptoms are gastrointestinal. Tiiere is immediate vomiting, followed by tenesmus and bloody discharges from the intestines. Death is infrequent, but there may develop a condition of hemorrhagic inflammation in both the large and the small intestine which is called by Richet "chronic anaphylaxis.'' and by Schittenhelm and Weichardt, enteritis anaphy- lactic*. " Another important sign is the rapid fall in blood pressure, sometimes 80 to 100 millimeters; coagulation of the blood is delayed. Dyspnea is not marked, but as in other animals, there are initial rest- lessness and skin irritability 7 ; there may be paralysis and death. Rabbits are apt to react to a reinjection of horse serum by edema and even necrosis at the site of injection — the "Arthus phenomenon" or local anaphydaxis. Arthus also described, in non-fatal cases in rabbits, respiratory 7 disturbance, general prostration, fall in blood pressure, and increased peristalsis. In cases of acute lethal anaphylaxis produced in rabbits highly 7 sensitized by repeated minute injections, Auer describes the slow 7 respiration, the sudden falling of the animal on its side witli a short clonic convulsion, stoppage of the respiration, weak heart beat, and death within a few minutes. Auer believes, from observations made at immediate 311 Anaphylaxis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES autopsy and by actual inspection of the chest contents during shock, that acute anaphylactic death in rab- bits is due primarily to a failure of the heart muscle to perform its work, and not to a condition in the lungs causing asphyxia, as in guinea-pigs. The lungs collapse well, "though not fully; but the right heart remains dilated, and its muscle is seen to be changed anatomically and functionally, as though in chemical rigor. Altered reaction to a second injection of serum has been observed, though not studied so carefully, in numerous other animals, e.g. in cows, horses, goats, sheep, and cats, in hens and pigeons, and in certain cold-blooded animals, with symptoms varying accord- ing to the species. It is evident that no one symptom, or group of symptoms can be taken as an adequate criterion of anaphylaxis in all cases. For while the symptoms of anaphylactic shock are characteristic and practi- cally constant in the same species of animal, a differ- ent species will give a widely differing picture with the same protein agent, because the same organs are not involved to the same degree. An explanation of these differences from the physiological point of view has been given by Schultz. He has shown that serum anaphylaxis is essentially a matter of hypersen- sitization of smooth muscle in general. He concludes, as a result of his experiments that during anaphy- lactic shock, all smooth muscle contracts. This is fatal to the guinea-pig owing to the peculiar though normal anatomical condition of its bronchial tree; the mucosal layer of the secondary bronchi is relatively thick in comparison with the lumen, and the contrac- tion of the smooth muscle throws it into folds which completely occlude the bronchi (Schultz and Jordan). The guinea-pig dies of asphyxia the cause of which is purely local and not in the central nervous system, as the first investigators believed. Auer and Lewis had previously shown the same thing by producing immobilization of the lungs with a toxic dose of pro- tein in sensitized animals whose cord and medulla were destroyed. The bronchi of mice, dogs, and rabbits, however, are relatively poor in mucous membrane, which accounts for the almost complete absence of death from asphyxia in the animals during anaphylaxic shock. In the dog the contraction of smooth muscle sets up a vigorous intestinal peristalsis and a forced emptying of the urinary bladder; the characteristic initial rise in blood pressure may be due to constriction of the pulmonary, coronary, and systemic arteries, and according to Auer the sub- sequent marked fall to direct action on the heart muscle itself, particularly of the right side, causing a venous accumulation of blood, an effect typified most strikingly in the rabbit. This provides also an ade- quate pharmacological explanation of the action of atropine and the anesthetics in alleviating the symp- toms of acute anaphylaxis. Serum anaphylaxis in man is met with most fre- quently following the use of antitoxic sera and has been carefully described by von Pirquet and Schick (1005). After an injection of scrum (usually in from eight to twelve days) there is apt to be a febrile reaction, now generally known as "serum-sickness." The common symptoms are local redness, itching, and pain at the point of injection, swelling of the lymph nodes, fever, and a general urticaria lasting from two to six days. In more severe cases there are general malaise, albuminuria, pronounced joint pains and even effusions, swelling of the mucous membranes, hoarseness and cough, nausea and vomiting, vertigo, and remarkable skin manifestations varying from hyperemias and erythemas to efflorescences resem- bling measles or scarlatina. Rarely there may be subnormal temperature, a weak and rapid pulse, a catarrhal or hemorrhagic enteritis and extreme weakness approaching collapse. These results are independent of the antitoxic quali- ties of the serum, for Johannessen obtained the same symptoms by introducing normal horse serum into the bodies of perfectly healthy human beings. Indeed the very earliest animal experiments were particu- larly concerned in determining whether the antitoxin played any part in the phenomenon and it was soon conclusively eliminated as a factor. Both the incidence and the severity of serum sickness are proportional to the amount injected up to. a certain point, but the acute (sometimes fatal) reaction in man is more dependent upon the hyper- susceptibility of the individual than upon the amount of serum injected. If the serum is "concentrated" (i.e. serum-globulin) the reactions are correspondingly lessened because smaller quantities of the foreign protein are injected, and the albumins and certain other proteins have been eliminated. If the serum be properly aged (a year or two old) the incidence of serum-sickness is believed to be decreased. The peculiarity of serum sickness in man is that it may follow the first injection of a foreign serum, though only after a definite incubation period corresponding to the time required to sensitize an experimental animal. It has been suggested that enough serum remains unchanged or incompletely changed near the point of injection to cause a sharp reaction when the body becomes sensitized. There is no proof more- over that other animals do not develop a reaction to the first dose which never rises to the threshold of clinical observation. In fact Ehrlich, Francione, and others have observed a temporary diminution of complement in the blood of guinea-pigs ten to twelve days after the first injection. A second injection of serum after some days finds the human organism in a sensitive condition and if a clinical reaction is produced, it is, as we might expect, immediate and often severe, but of shorter duration than the first. Von Pirquet noticed that if many months or years elapsed between the two injections, the reaction was no longer "immediate" but only "accelerated," coming between the sixth and eighth days instead of between the eighth and twelfth days which is the normal incubation period for serum sick- ness. He concluded that sensitiveness may disap- pear in course of time, but is more quickly regenerated on a second occasion. Besides the typical serum sickness, there have been reported since the introduction of serum therapy a certain small number of unforeseen and fatal catas- trophes attending the injection of serum into human beings. The following case published by H. F. Gillette will serve to illustrate them all: " The patient was a man of fifty-two, a subject of asthma. He asked me to administer diphtheria antitoxin to him hoping it might cure his asthma. I administered 2,00(3 units under the left scapula with the usual precautions. He had about com- pleted dressing when he said he had a pricking sensation in the neck and chest; soon he sat down and said he could not breathe, nor did he breathe again. His pulse at the wrist remained regular and full for some time after respiration ceased. He had a mild degree of cyanosis and edema of the face. He died in tonic spasm ten minutes after injection. Autopsy revealed no palpable cause of death." The same author collected twenty-eight cases of collapse or death after serum injection, of which fifteen ended fatally. There was a common history of previous asthmatic trouble in all but five of the twenty-eight, and all, after injection, showed common symptoms of sudden intense dyspnea, a sense of overwhelming anxiety, edema and cyanosis of the face, a sudden massive urticaria, tonic muscular spasms, and con- tinued beating of the heart long after the ceasing of respiration. Rosenau and Anderson collected nine- teen cases and were able to examine the serum used in two of them. It was found to be no more toxic to sensitized guinea-pigs than other horse serum. These 312 REFERENCE HANDBOOK OF THE MEDICAL SCIEM T,S Anaphylaxis rases of severe systemic shock seem susceptible of no other explanation than that the unfortunate individ- uals had been in some manner at a previous time sensitized to horse protein. They present a picture which is almost the counterpart of typical anaphylactic shock in guinea-pigs, and the most striking thing n them is that practically all give a history of piratory trouble in the past, especially horse- ,1,1a. Schultz and .Ionian suggest that these occasional cases of sudden death in man may perhaps be due to an abnormal development or condition of mucous membrane and smooth muscle of the bronchi (as in asthmatics), and that the smooth muscle, being hypersensitive, produces asphyxia by sudden contraction. One thing is clear, that (hese immediate and sometimes fatal reactions are not dependent upon any peculiar property in the in. bul to an altered powered of reaction of the individual to the foreign protein injected.* The anaphylactic reactions following the injection of serum in man may l>e summed up briefly as follows: Reactions following first injection: 'Serum sickness," incubation eight to twelve days. Vcute anaphylactic shock, with collapse or death i rarely). Reactions following second injection: interval between injections less than eight days, iction. b | interval twelve to forty days, immediate reaction. c) interval fifteen days to six months, either immediate or accelerated reaction, or both. ,/ interval over six months, accelerated reaction. The above table represents the usual course of events, but exceptions may occur, and the time intervals are only approximate. Sometimes the reactions in man do not appear until the third, fourth, or some subse- quent injection. Two precautions are suggested in serum therapy: 1. Except in urgent cases, avoid injecting horse serum into individuals known to be asthmatic, or to have symptoms when around horses. 2, If hypersensitiveness is suspected, give at first a very small portion of the dose, following it in an hour or so with the rest, injecting it exceedingly slowly and avoiding a direct injection into the circulation. Experimental Anaphylaxis. — 1. The Anaphy- lactic Agents, or Allergens. — A great variety of pro- teins, animal, vegetable, and bacterial, can induce hypersensitiveness. Such substances also give rise to antibodies, and are therefore true antigens; toxins which are also antigens are not able to produce a -late of true anaphylaxis. Gelatin, a protein of a Eeculiar sort, is not an allergenic substance. This as led to the supposition that sensitizing power has some connection with the aromatic radicle of the pro- tein molecule, which is not found in gelatin. The stability of anaphylactic antigens is remarkable. Chemicals can destroy the sensitizing power only by breaking down the protein molecule into cleavage products as low as peptones. The antigens are ther- mostable to a high degree. Eel serum, naturally a very toxic substance, is rendered quite non-toxic at 60°, but its sensitizing power is unaffected. When ths physical state of a substance is altered by heat, as in coagulation, its allergenic properties disappear, but if coagulable substances such as egg-white, horse serum and milk are first carefully dried, thev may then be heated to 130° C. for two hours, or to 170° C. for ten minutes without appreciably affecting their ♦Rosenau and Amoss have recently indicated a possible explanation of the way in which such persons may become sensi- tized. They have proved that a protein material is given off in the expired breath of human beings. There is thus some reason to suppose that an interchange of protein may take place between two individuals of different species by way of the lungs. anaphylactic powers i Rosenau and Anderson). \:e also is proved to have no appreciable effect, Bince I'lilenhuth has sensitized animals with the flesh of mummies. An incredibly small amount of ant igen is sufficient to induce hypersuseept ibilii v. Uoseiiau and Ander- son used on an average 0.004 CC. of serum in their experi ntS, and once sensitized a guinea-pig with one one-millionth of a cubic, centimeter. Well; sensitized a guinea-pig with such a minute amount as one twenty-millionth of a gram of purified egg-albu- min. The first injection or sensitizing dose may be given subcutaneously, intraperitoneally or directly into the circulation. In fact, susceptible animals may be sensitized by intrpducing the alien protein into the body by any route through which it may be absorbed. For example, guinea-pigs have been sensitized by the inhalation of a fine spray of serum, and even by tier ingestion of horse serum or horse meat over a period of two or three weeks (Rosenau ami Anderson). As an interesting parallel to the latter fact Uhlenhuth has shown that precipitins are formed in the blood after the prolonged ingestion of meat and Carrol has induced the production of specific agglutinins by the ingestion of dead typhoid bacilli. The second injec- tion or reacting dose must be relatively larger than the sensitizing dose, but the actual quantity required to produce poisonous symptoms is nevertheless very small. One-tenth of a cubic centimeter of horse serum injected into the peritoneal cavity is sometimes sufficient to cause death in a sensitized guinea-pig; 0.1 c.e. subcutaneously may cause symptoms, while much smaller amounts given into the brain or directly into the circulation may be fatal. Proteins vary in this respect; for example, egg-white is effective in even smaller quantities than horse serum at the second injection, whereas a larger amount of milk is necessary to produce an equivalent reaction. The anaphylactic reaction is specific. Thus a guinea-pig sensitized with horse serum does not react to a subsequent injection of egg-white, vege- table protein or milk. The specificity extends even further than this: in order to give rise to anaphylactic symptoms, the protein material given at the first and second injections must be from the same species or from some closely related species. Thus a guinea-pig sensitized with cow's milk will not react to a subse- quent injection of woman's milk. Guinea-pigs sensitized with the albumin of hen's eggs will not react to a subsequent injection of the albumin of the eggs of pigeons, but do react mildly to duck egg-white (Rosenau and Anderson). This specificity according to species is therefore of the same degree as that of certain immune reactions, notably the precipitins. That is, there is a group reaction in the proteins of allied species, but no reaction between the proteins of widely different species or between proteins of widely different origin. The maximum effect at second injection is obtained by the use of the identical protein used for sensitization. Certain sera which react interchangeably to precipitins, as, for example, human and ape, horse and ass, sheep and goat, rat and mouse, remain indistinguishable also by the anaphylactic reaction. The same specificity holds with respect to bacterial proteins: an animal sensitized with typhoid bacilli will react strongly toward paraty- phoid, and somewhat toward colon bacilli, but not at all to unrelated species. One of the remarkable facts in relation to the specificity of anaphylaxis is that guinea-pigs may be in a condition of anaphylaxis to three protein sub- stances at the same time. For instance, a guinea- pig may be sensitized with egg-white, milk and horse serum, and subsequently react separately to a second injection of each one of these substances. The guinea-pig may be sensitized by giving these strange proteins either at the same time or at different times, 313 Anaphylaxis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES in the same place or in different places, or by in- jecting them separately or mixed. The guinea-pig differentiates each anaphylactogenic protein in a perfectly distinct and separate manner. The animal is susceptible to the second injection of each one of the three substances in the same sense that it is susceptible to three separate infectious diseases (Rosenau and Anderson). That there may be exceptions to the rule of species- specificity is shown in the case of the crystalline lens. A guinea-pig sensitized to the lens-extract of one species of animal will react to the lens-extracts of widely different species, or even of its own species but not to other tissues (Andrejew). Here too there is an exact parallel in the precipitin reaction which fails to distinguish the lens of one species from that of another (Uhlenhuth). This is an example of organ- specificity. It is said, but without definite confirma- tion, that the tissue of the uveal tract, and of neo- plasms also contain organ-specific proteins. In the vegetable world, Osborne has shown that whereas preparations of globulins from hemp, flax, and squash do not react with each other, gliadin from rye reacts strongly with gliadin from wheat, a result in accord with the fact that by chemical and physical means, no differences have been detected which were sufficient to indicate that these gliadins were different substances. It is probable that only proteins which have a complete or partial chemical identity of structure will react with each other. Differences too small to be detected by analytic means at our disposal, may yet prevent any tendency toward interaction, and the anaphylactic phenomenon may thus be used to deter- mine the finer relationships of proteins. It is evident from these facts, as Osborne concludes, that struc- tural differences exist between very similar proteins of different origin, and that chemically identical proteins apparently do not occur in animals and plants of different species unless they are biologically very closely related. The identity of the sensitizing with the intoxicating substance has been frequently brought into question in the past. Besredka, Vaughan, and others report results which led them to the conclusion that anaphy- lactic antigens contain two separable substances, one of which acts as sensitizer, the other as the reacting agent. The impossibility of obtaining, at present, a chemically pure protein to work with, renders it difficult to establish this point. Wells, however, has shown that the purer the protein, the smaller is the amount necessary both to sensitize and to intoxicate, a fact pointing to the identity of the two substances. Rosenau and Anderson as well as Doerr and Russ have shown that both qualities of a foreign serum are affected equally by age, heat, and other modifying influences, indicating that both phases of the anaphy- lactic phenomenon have to do with one and the same sul i-tance. 2. Incubation Period. — Sensitization in an animal appears only after a period of from eight to twelve days after the first injection. This corresponds to the incubation period of a large group of the infectious diseases, and to that of serum-sickness in man. That infection and sensitization are in some way correlated phenomena has long been believed. Von Pirquet's explanation of the incubation period of both in common terms of "allergy" with be discussed later. A second injection, given within the incuba- tion period, produces no symptoms of reaction, and indeed postpones or prevents the appearance of sensitization. Similarly it has been said that a large initial dose prolongs the incubation period. However, once the condition of hypersensitiveness is established, it lasts (with perhaps a slight but gradual waning of intensity) for an indefinite period. The exact limit is not known, but Rosenau and Anderson have found a guinea-pig highly sensitive 1,096 days after the first injection, and they believe that the condition is persistent throughout life. 3. The Refractory Slate (antianaphylaxis, anergy immunity). — If a sensitized animal recovers from acute anaphylactic shock, or is given a second comparatively large dose of protein within the incubation period, it immediately enters a so-called refractory state or antianaphylaxis (Nicolle), in which it is "immune" to further injections of that particular protein and acts like an animal that has never been sensitized. The state of antianaphylaxis is not believed to be a true "immunity" in a serological sense, becau.-e it appears at once, without any incubation period; it disappears in the course of a few weeks leaving the animal again sensitive; and the serum of refractory animals is not protective against anaphylaxis when introduced into other animals, but on the contrary actually confers a condition of hypersensitiveness. No adequate explanation of this state has been advanced; it is commonly attributed either to dis- appearance of complement, which is apparently a necessary factor in anaphylactic shock, or to neutral- ization (saturation) of the antibodies upon which the state of hypersensitiveness seems to depend (Friedberger). A pseudo-refractory ' state may be induced by certain drugs, notably the anesthetics which merely mask the symptoms of shock by paralyzing the central nervous system; or by large intravenous injections of physiological salt solution, which seem to prevent shock by temporary deviation of complement. A correct conception of this interest- ing phenomenon of antianaphylaxis is not possible until we have mastered the fundamental principles underlying anaphylaxis. 4. Passive Hypersusceptibility (passive anaphy- laxis). — Otto was the first to describe the passive sensitization of guinea-pigs. He noted that if serum from a sensitized animal be transferred directly to a normal animal, the recipient becomes hypersuscep- tible without the intervention of the usual incubation period and remains hypersusceptible for one or two weeks. Otto, Gay, and Southard, and others found that a latent period of about twenty-four hours must elapse after the transference of serum before a reaction could be elicited. It has recenth' been stated (Doerr and Russ) that under proper conditions, an immediate passive hypersusceptibility can be obtained. This would make the condition analogous to passive immunity and it is generally known therefore as "passive anaphylaxis." At the same time, as Hektoen points out, the period of latency observed in so many of the experiments in passive anaphylaxis has not been explained altogether satisfactorily. Furthermore, it has not been conclusively proved that sensitiveness is capable of heterogenous trans- mission, i.e. from one species to another, as in the case of passive antitoxic immunity. Hypersuscepti- bility is transmitted by the mother guinea-pig to her young, which may remain sensitive for as much as a year after birth. This fact (as first pointed out by Rosenau and Anderson) may throw some light on the transmission of a tendency to a disease from generation to generation. 5. Local Anaphylaxis. — The fact that a second subcutaneous injection of alien protein in a rabbit may cause local edema and necrosis instead of acute systemic shock has been referred to as an example of local anaphylaxis. The ocular instillation of tuberculin may lead to a sensitization which is local to a certain extent, and w-hieh renders a subsequent application liable to misinterpretation. In experi- ments by Rosenau and Anderson, out of twelve men who gave an absolutely negative test to the first conjunctival application of tuberculin, ten reacted typically to a second application of the same material after an interval of fifty-one days. Bloch infected himself with a new species of ringworm which he 314 REFERENCE HANDBOOK OF THE MEDICAL SCIKXCES Anaphylaxis ,■ ., Isolating, and two years later found thai he still gave a vigorous cutaneous reaction to an extract of the fungus, prepared like tuberculin. He now skin- grafted a patient from himself, and discovered thai these graft 3 continued to give a cuti-reaction toward the same extract, although the patient's own skin failed to react. This bespeaks a local effecl upon the in addition to changes in the blood during certain forms of sensitization— in other word-; ana- phylaxis is probably a cellular as well as a humoral omenon. Practical Relation of Anaphylaxis to Medi- , im . -One effecf of serum therapy (viz. serum-sick- i:i- been noted above, but ol her forms of treat- ment in which protein matter is injected are liable to be followed by anaphylactic manifestations. In the Pasteur prophylactic treatment for rallies for example, there is apl to be a sudden and simultaneous Baring up of previous points of inoculation sometime during the second week. Vaughan reports a case receiving the Pasteur treatment for the bite of a rabid dog in January, 1906. In March, 19U7, the patient was bitten by a rabid cat and received a second course of treatment. Each injection produced almost at once a local area of aseptic inflammation three inches in diameter which disappeared in forty-eight hours. The patient 's sister who received the same emulsion I no reaction. Hay fever and asthma form a group of diseases which are undoubtedly anaphylactic in origin. The different types of hay fever are characterized by uniform symptoms at definite seasons, namely, redden- ing and swelling of mucous membranes and watering of the eves, sneezing, asthma, and a soreness in the throat and larynx. Elliotson in 1831 showed the cause to be pollen. The disease can be produced at will, even in winter, by exposing sensitive individuals to pollen; normal persons do not react. Appreci- ation of this reaction as a phenomenon of hyper- sensitiveness is due to Wolff-Eisner from whose monograph the following data are taken. The pollen test consists in suspending one centigram of pollen in 5 c.c. of salt solution, and instilling two drops into the eye. Normal persons feel a slight itching, but sensitive individuals react with typical symptoms: the conjunctivae become injected and rapidly che- motic; the nasal mucous membrane swells and there are sneezing and asthma. The analogy to serum disease and to hypersensitiveness to tuberculin is strength- ened by the fact that the same symptom-complex may be obtained by subcutaneous injection of the pollen suspension, in which case an urticaria develops about the point of inoculation as well. Asthmatics of the various types presumably are sensitized to different protein substances found in their environ- ment. Tims certain individuals may have symp- toms of hay fever (including asthma) in the presence of horses, rabbits, guinea-pigs and other animals. Many substances, which as far as can be discovered, possess no inherent toxic properties of their own, and to which the vast majority of human beings are utterly insensible, cause in certain people intense inflammatory reactions when they are brought into contact with their bodies, either directly upon the skin or in the alimentary tract. Of the external irritants cases have been reported of severe general urticaria following contact with satinwood, prim- roses, and many other substances. Idiosyncrasies with regard to articles of diet belong to the same ■ gory. Apparently almost every variety of protein food has at some time or other been reported as intolerable to certain individuals. Buck had a patient who was sensitized to pork and suffered urticaria whenever he ingested it in any form or any quantity. Ten cubic centimeters of the patient's serum were put into a guinea-pig, which twenty-four hours later reacted with acute fatal anaphylactic shock to 5 c.c. of pig serum, evidently an example of passive anaphylaxis. Egg-albumin not infrequently produces the most severe gastrointestinal disturb- ances, with vomiting ami watery diarrhea, as well as a generalized urticaria ami asthmatic crises even when disguised in minute quantities in other funds. Egg-white as well a-, any other protein substance to which the individual has bet le sensitized, may produce; a local reaction when rubbed into the skin. This is analogous to the von Pirquet reaction with tuberculin, which will be discussed later. All forms of sea-f 1 (oysters, lobsters, fish, etc.) an' notorious intoxicating agents in some people, and among the vegetables, buckwheat, tomatoes, and strawberries may cause the same unpleasant effects. In such cases, it is unknown how the sensitization is originally 'Heeled, but both the alimentary and respiratory t ract s have been suspected. Besides serum-sickness, hay-fever, as well as most of t he asthmas and urticarias, w hich are now generally accepted as anaphylacl ic in nature, there are a number of other phenomena which are now being explained in terms of anaphylaxis. Light is thrown on puerperal t clampsia by the fact that a pregnant guinea-pig can be sensitized to her own placental extracts (Rosenau and Anderson) and probably to her own amniotic fluid and the serum of her young. This sensitive- ness has also been passively transferred (Gozony and Wiesinger). Hektoen points out the fact that sympathetic ophthalmia may be an allergic phenome- non, since it has been shown that the lens protein and possibly also uveal tract protein may cause antibodies in the same animal from which they are obtained. The tuberculous diathesis (as well as other diatheses) is explained in part as an hereditary transmission of hypersusceptibility. And anaphylaxis has been sug- gested now and again as a factor in the onset of labor, the crisis in pneumonia, the spasmophilic diathesis, the symptoms attendant on the rupture of the cysts in echinococcus disease, and the effect of quinine in suddenly liberating hemoglobin in black-water fever. Anaphylaxis in Diagnosis. — The most important of the special anaphylactic phenomena are the tuberculin and mallein reactions. The hypodermic injection of tuberculin was intro- duced by Koch in 1S90, but its diagnostic as well as its therapeutic use was abandoned for a long while, when its dangers were discovered. The reaction was determined by the rise in temperature. In a tubercu- lous individual, the temperature rises in six to twelve hours, is at its height from twelve to twenty-four hours, and declines to normal in twenty-four to thirty- six hours. The patients compare their symptoms to those of grippe; headache, prostration, pains in the joints and limbs. In 1907 von Pirquet introduced the cutaneous tuberculin test, in which a drop of "old" tuberculin is placed upon a scarified point on the skin. The specific reaction appears within twenty-four hours as a red papule at least five milli- meters in diameter. The reaction reaches its maxi- mum in forty-eight hours and fades out slowly, ulti- mately leaving no trace. Simple contact of the outer skin with "old" tuberculin is sufficient for the specific reaction where there is a high degree of sensitiveness of the skin (Lautier). Upon intense rubbing with a fifty per cent, tuberculin ointment (Moro's percu- taneous test) the reaction is nearly as delicate as the cutaneous. The mucous membranes are even more sensitive than the skin, e.g. the conjunctiva, nose, urethra, rectum, and vagina. In all tests a non-sen- sitized person will give no reaction. The explanation of this advanced by Koch was that the small addition of the injected tuberculin to the antigen already in the body is sufficient to cause general symp- toms. Marmorek thought the dose stimulated old foci to renewed activity. It is now generally accepted as an anaphylactic reaction. Indeed it is analogous to the "accelerated reaction" in serum disease. 315 Anaphylaxis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Tuberculin is believed to be a suspension of ultra- microscopic particles of the protein material contained in the bodies of tubercle bacilli. The old tuberculous focus plays no part except as the sensitizing agent; the tuberculin injection or cutaneous application acts as the reacting dose. It is the rapid destruction of the protein material by the prepared organism which liberates poisonous products and gives rise to symp- toms of local inflammation, or of systemic reaction. Both the prevention and cure of tuberculosis may be explained on the basis of anaphylaxis. The power of defense against the tubercle bacillus is directly pro- portional to the power of the body to react and thus prevent the invasion, growth, and multiplication of the parasites. If a tubercle bacillus lodges in a sen- sitized organ or tissue, a vigorous reaction takes place at once. The bacillus is attacked by the cells and fluids which are concentrated upon the point where they are most needed. If the organ or tissue is not sensitized, no reaction occurs and the natural defences of the body are not brought into operation; little or no obstacle is presented to the development of a tuberculous focus. The cure of tuberculosis also depends upon the power of the tissues to react in the anaphylactic sense. Thus, the tissues immediately surrounding a tuberculous focus become sensitized by the autolytic products of the tubercle bacillus. The power of such tissues to react may be seen with the naked eye as a red zone of congestion when tuberculin is injected into such an animal. The cure of tuberculosis depends upon the ability of the surrounding tissues to react promptly and vigorously enough to wall off and thus neutralize or destroy the tuberculous focus. In case the power of reaction fails, the primary focus spreads and the disease advances to a fatal termination. If instead of the minute quantity of tuberculous material which gains entrance into the animal body by natural or artificial inoculation, we inject large amounts of tubercle bacilli into infected animals, we get very intense and usually fatal anaphylactic symptoms, which are elicited equally by living or dead bacteria, or by bacterial extracts. Von Pirquet points out that the tuberculin test fails under the following conditions: 1. Very early in life, i.e. in nurslings. Schlossman and Moll found that serum disease also is very rare in nurslings. This led them to experiment on rabbits, and they showed that no demonstrable antibodies (such as precipitins and agglutinins) are formed before the eighth week, and that injections of albumin pro- duce no anaphylaxis during this period. 2. In advanced stages, in chronic or cachectic forms, in miliary tuberculosis, and in tuberculous meningitis, tuberculin tests fail. This is probably due (according to von Pirquet) to saturation of the antibodies owing to preponderance of antigen (antianaphylaxis?). 3. Continued treatment with tuberculin will destroy the reaction for the same reason. 4. A long interval following a healed infection will allow the antibodies to disappear. The mallein and leprolin tests in the diagnosis of glanders and leprosy are precisely similar in theory and practice to that of tuberculin. A similar test has been put to use in actinomycosis. The recent preparation of syphilitic virus in the form of " luet in" by Xoguchi, may perhaps offer a similar opportunity to diagnose syphilis by a cutaneous test. Individuals with many other bacterial infections will respond to the cutaneous or conjunctival application of the corresponding bacterial extract, and the test has been proposed in typhoid fever, gonorrhea, pneumonia, and other diseases. Passive anaphylaxis has been tried, but rather un- successfully as an aid to diagnosis of tuberculosis and cancer. Yamanouchi (1908) claimed to have sensi- tized rabbits passively with serum from tuberculous pa- tients or cadavers, and Capelle has recently (1911) transferred sensitiveness to tuberculin from one animal to another. These results have not been rigidly confirmed, nor applied in any practical manner toward the diagnosis of the disease. According to Pfeiffer the serum of cancer patients renders guinea- pigs passively sensitive to cancer proteins. The assumption is that the cancer protein is specifically different from that of the host. This, if confirmed, would aid not only in the diagnosis of malignant dis- ease, but in its treatment. The anaphylactic reaction has forensic value in the identification of blood stains. Thomsen at the State Serum Institution in Copenhagen easily rendered guinea-pigs anaphylactic to homologous serum by means of an aqueous extract of the blood spot in question. The specificity of the reaction has made it valuable in the detection of protein adulterants in food, such as horse meat in sausages, etc. Anaphylaxis as a Scientific Instrument. — In the detection of minute quantities of protein, and in the study of the relationships of different proteins, the anaphylactic reaction is invaluable. Rosenau and Amoss have determined that the expired breath of human beings contains protein material enough to sensitize guinea-pigs, a fact which may have a bearing on the cause of symptoms in crowded, ill-ventilated places, and also offers an explanation of the way in which individuals may become sensitive to horse serum and some other foreign proteins. In cases of alimentary albuminuria, "Wells has found by this reaction that the albumin excreted is not chemically identical with that ingested. Doerr has suggested using anaphylaxis in the differentiation and grouping of bacteria. The potentialities of the anaphylactic reaction are therefore rather broad in the domain of scientific research. A limitation in the practical application of anaphylaxis is that the only method of observing the reaction is in the production of acute symptoms in experimental animals, a test at present less capable of accurate, quantitative determination than hemolysis or precipitatii in in a test-tube, and of no greater specificity. On the other hand, the minute quantity required for sensitization gives anaphylaxis a certain advantage over other specific tests. Theory of Anaphylaxis. — The literature on this subject is already immense; the basic facts upon which it is founded are few and somewhat contradictory. In general, the theories may be divided into those which assume the formation of specific antibodies as necessary to the anaphylactic state, and those which dispense with antibodies altogether as a factor in the phenomenon. Examples of the latter group are Gay and Southard's " anaphylactin " theory and Vaughan's "proteolytic enzyme" theory, neither of which can be discussed here for want of space. The prevailing view is that sensitization depends in some way upon antibody formation, and that the anaphylactic reaction is essentially an antibody reaction. This theory finds support in the facts already noted above, namely, (1) all anaphylactic agents are true antigens; (2) the incubation period agrees precisely with that necessary to the production of antibodies; (3) complement is a necessary factor in the anaphylactic reaction; (4) hypersusceptibility is capable of passive transference in serum; (5) in point of specificity it bears the closest relation to the immune reactions of the second order (Ehrlich), particularly the precipitin reaction. In its simplest terms, the present conception is that the sensitizing dose of anaphylactic antigen gives rise after the usual period, to substances of the general nature of amboceptors. These combine with the reacting dose of antigen and form with the aid of complement, poisonous products which cause the anaphylactic symptoms and lesions. These toxic substances according to Vaughan are protein cleavage products formed during the sudden destruction of the antigen 316 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anaphylaxis in the body of the sensitized animal. He has pro- duced from ege-albumin, by chemical means, cleavage products which are exceedingly poisonous and cause death in guinea-pigs resembling that of acute lethal anaphylaxis. Friedberger has mixed together an- tigen, complement, and serum containing the supposed antibodies in a test-tube and has obtained a poisonous product (anaphylatoxin) of which a single injection in a guinea-pig causes symptoms like those of acute anaphylactic shock. This is the so-called "ana- phylaxis in vitro." He concludes that the antigen is first precipitated and then destroyed by specific antibodies which have all the characteristics of pre- cipitins. Opposed to this theory Is the very minute amount of antigen required to produce a high degree of itization, and the further fact that although the ipitin reaction is very clear in the rabbit, the anaphylactic reaction is much less intense than in the guinea-pig in w hich there is a very small production of antibodies of any sort. Many other theories have : proposed, but as yet none is regarded as entirely satisfactory, for it seems plain that the cells as well as the blood and allergenic substance play a role in tin- phenomenon. Rklation op Anaphylaxis to Infection and Im- munity. — The experiments of Vaughan with egg-white and those of Friedberger with bacterial proteins have led them to the conclusion that infection and anaphyl- axis are different expressions of the same proce Vaughan finds that cleavage products of egg-white and other harmless proteins are quite as toxic as the cleavage products obtained from the bodies of patho- ■ bacteria. We might suppose that if egg-white Id grow and multiply in the animal body, it would as a result of such growth and subsequent age by proteolytic antibodies be just as deadly as the bacilli of the infectious diseases. In fact, in the invasion of the body by bacteria, the incubation period necessary for the education of the tissues to produce antibodies, the destruction of the bacteria with the simultaneous appearance of symptoms and lesions,and the storing of the surplus antibodies, we have an exact if theoretical analogy to our conception of the processes leading to "serum-sickness." In other words, the question is whether in bacterial diseases we have to do with preformed endotoxins or with the poisonous cleavage-products of a protein substance endowed with the powers of growth and reproduction. Rosenau and Anderson, Friedberger, and many others have shown that bacterial protein acts like any other antigen in producing acute anaphylactic -hock, if injected a second time in sufficient quantity. Rosenow, after much patient work with the pneumo- coccus has shown that autolytic products of disinte- grated cocci will cause anaphylactic symptoms in a tea-pig at the first injection. These facts have led I i iedberger to hazard the conclusion that anaphylaxis is only an extreme and acute form of infection, and infection a mild, protracted form of anaphylaxis. It cannot be said that this view is as yet justified, but it is at least an interesting and suggestive theory. The exact relation between anaphylaxis and immunity is not yet clearly understood, although all workers in the field have recognized that there must be a close connection between the two, on account of the many striking analogies, already recounted under the heading -'Theory of Anaphylaxis" and elsewhere in this article. The clearest elucidation of the two processes as part and parcel of the same general phenomenon has been furnished by von Pirquet. In his own words, "an immune person does not become insensible to inoculation, but the time, quality, ami quantity of his reaction are changed." He would combine therefore the conceptions ,of immunity and hypersensitiveness in the one work "allergy" — or the changed reactivity of an organism to a second invasion of a foreign antigen. Of all the infectious diseases conferring immunity, the one best luted lor experimental and clinical study in man is COWpoX, or vaccinia. When we vaccinate for I lie first time, we note a fairly constant symptom-com- plex, tin the third or fourth day a small red papule appear- which is the specific la- distinct from the traumatic) reaction. From the fourth to the sixth day the middle of the papule bee ! elevated into the papilla, and is surrounded by a flat, peripheral "areola" or zone of inflammation. From the eighth to the eleventh day we see firs! a vesile, then a pustule which is attended by fever and leucopenia. from tin- time the reaction subsides, leaving the well-known vaccina- tion scar. If we revaccinate daily for a fortnight, the papillae appear in order uninfluenced by each other; but the "areola" appears on all the vaccination points simultaneously, i.e. at the time when its development is due on the first vaccination. From this time on, no papillse develop; we get another type of reaction — the "early reaction" — in which the papule is at its maximum in twenty-four hours, then disappears. This occurs whenever vaccination is repeated. Some years later, we get a "torpid early reaction," or accelerated reaction, in which the maximum comes on the third or fourth day. Just as in serum sickness, the altered reaction (allergy), which follows reinoculation with the antigen, ex- presses itself temporally in a shortened incubation period, quantitatively in a heightened intensity of reaction which is, however, of short duration, and qualitatively in the kind of lesions produced. It is interesting at this point to refer to Jenner's own observation of this phenomenon, recorded in 1 798. He says, " It is remarkable that variolous mat- ter, when the system is disposed to reject it, should excite inflammation on the part to which it is applied more speedily than when it produces the smallpox. Indeed, it becomes almost a criterion by which we can determine whether the infection will be received or not. It seems as if a change, which endures through life, had been produced in the action, or disposition to action, in the vessels of the skin: and it is remarkable, too, that whether this change has been effected by the smallpox or the cowpox, the disposition to sudden cuticular inflammation is the same on the application of variolous matter." This remarkably clear statement (quoted by Hektoen) probably records the first observation of allergy in an infectious disease. The actual processes underlying these different types of reaction are described by von Pirquet as follows: We implant a colony of microorganisms on the skin. They grow day by day, and on the eighth i lay there are an enormous number of them. The contents of the blister will start new colonies on thousands of other arms. But now the antibody appears and the colony is attacked and digested, and a toxic body formed. This is diffused in the neighbor- hood and we get an intense local inflammation called the areola. Some of the toxic bodies enter into the circulation and cause fever. But the microorganisms are killed and we can no longer vaccinate with the contents of the now yellow pustule. After two or three days, the struggle is over, but the antibodies remain a long time. Let us now- revaccinate. The microorganisms are immediately attacked and di- gested — they are given no chance to multiply and little toxin is binned. This is the immediate reaction. After a few years, antibodies are no longer present, but can be formed more quickly than the first time. This causes the accelerated reaction. A smallpox germ deposited in the throat of an unvaccinated individual, multiplies without opposition throughout the incubation period, and the individual goes through the whole course of the disease. In the throat of a vaccinated person, it is overwhelmed by the early reaction in the first tw r enty-four hours; a slight 317 Anaphylaxis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES redness appears about its disintegrating body, and that is all. According to this attractive theory, then, infection produces sensitization, like the preliminary injection of horse serum or egg-white. A second inoculation of the same antigen, whether it be living pathogenic bacteria, or a tenth of a cubic centimeter uf foreign serum, produces an allergic reaction, differing from the first in time, quantity, and quality. The antigen is broken down with fulminating rapidity, and if the amount is minute, the reaction is correspondingly trifling. But if the amount of antigen is large (as in the guinea-pig experiment) poisonous cleavage products are liberated en masse, which overwhelm the organism and produce acute anaphylactic shock. New light is thrown on that mysterious factor in infectious disease, the incubation period. According to the usual theory, microorganisms have to reach a certain development before toxins enough are produced to cause symptoms. If this were true, one would suppose that in a body rendered somewhat immune by previous infection, microorganisms would grow more slowly and the incubation period would be pro- longed. But vaccinia (and serum-sickness) exhibits just the opposite condition. Von Pirquet concludes that in most diseases, the clinical reaction is not an immediate consequence of infection, but a phenom- enon of a more complicated nature, not explicable simply by the action of microorganisms and other foreign substances on the tissues, but involving the existence of a third factor which appeal's only some time after the first infection. Thus far antibodies have been numbered among the protective substances. Now it is conceived that disease may be due to the ac- tion of some antibodies and immunity is based, not on an acquired insensibility to virus, but on an altered power of reaction toward it. There are, then, three general theories of immunity in vogue today: Ehrlich's side-chain theory, Metchni- koff's phagocytosis theory, and the theory of the ana- phylactic or allergic reaction. Curiously enough each one of these apparently divergent theories is based upon the metabolism of the cell. In the side- chain theory, it is the hungry receptors seeking a chemical union with protein food molecules; in phagocytosis, it is the hungry ameboid cell engulfing protein food particles; and finally anaphylaxis is an adjustment to alein food proteins in the sense of a defence. All three theories are intimately concerned with protein metabolism. No one theory fully explains the mechanism of immunity to all diseases. Each has distinctive features, although all overlap more or less. The only satisfactory explanation of the immunity to a certain large and important group of diseases finds its solution in terms of anaphylaxis. Lewis Wendell Hackett. Anaplasia. — This word (from dm, again, and irk&ais a moulding) is used by some writers synonymously with anaplasty, having the meaning of a repair of in- jured parts by means of plastic operation. In 1893 its use in an entirely different sense was introduced by von Hansemann, who wished to designate by some specific term the morphological and physiological differences which exist between the cells of malignant tumors and those of the normal parent tissue. The type and character of the parent cells are usually preserved to some extent in the tumor cells which arise from them; as, for example, the cells of a squamous-cell carcinoma of the skin may undergo a horny change; those of an adenocarcinoma arising from cylindrical cells are more or less cylindrical in shape; the cells of an adenocarcinoma of the thyroid m iv produce a colloid-like substance; metastases of an adenocarcinoma of the liver may secrete a bile- like fluid; and the sarcomata arising from the chromatophores of the skin produce melanin. These resemblances uf tumor cells to their parent cells are not so marked as the differences which exist between them, both in morphological and physiological characteristics. The latter are shown by striking variations in size and form; by changes in the finer structure of the nucleus and cell body as shown by staining reactions (hyperchromatosis, hypochro- matosis, etc.); by abnormal cell-division forms; by the changed chemical character or total absence iif cell function; by increased vegetative activity(habit of growth); and by the tendency to undergo degen- eration. To all of these alterations in cell character which constitute malignancy von Hansemann would apply the term anaplasia, as opposed to heteroplasia and metaplasia. According to his view, the signifi- cance of these changes must be that the cells of ma- lignant tumors have lost in differentiation (Entdiffer- enzierung) and so have acquired the powerof individual existence. The manner in which the cells have undergone this change or the etiology of malignant tumors is not included in the meaning of the term. There can be no doubt that the use of the term anaplasia in this application is of great service, and though von Hansemann's views have "met with much opposition, it has gained a wide acceptance in modern pathology. As used now anaplasia em- braces all these qualities of tumor cells as shown in their lessened differentiation and increased poirer of independent existence. Various other expressions are also in use to indicate the same peculiarities of tumor cells, such as kataplasia (Beneke), "new cell- races" (Hauser), "reversion from organotypical to cytotypical growth" (R. Hertwig). For a fuller discussion of the problems of malignancy included under anaplasia see the article on Neoplasms. Aldred Scott Warthin. Bibliography. Von Hansemann: Studien iiber Specificitat, Altruismus und Anaplasia der Zellen, Berlin, 1S93. Die mikroscopische Diagnose der bosartigen Geschwulste, Berlin, 1S97. Anatomical Nomenclature, the Basle. — The expres- sion BNA is an abbreviated title for the Basle Nomina Anatomica, or anatomical nomenclature, adopted by the Anatomische Gesellschaft of Germany, during their ninth session at Basle, 1895. The list comprises some 4,500 terms, regarded as the most fitting de-d- ilations for the various structures of human macro- scopic anatomy. The terms were selected by a Commission of Anatomists, appointed six years pre- viously, by the Gesellschaft, at the instigation of the late Professor Wilhelm His, for the purpose of revising anatomical terminology. The official list is constructed in Latin under the various headings of Osteology, Myology, S3'ndesmology Splanchnology, Angiology, and Neurology. A large proportion of the terms embodied in the list were culled from the many synonyms already in use in the standard text-books of gross anatomy, or in anatom- ical monographs, preference in each case being given to the shortest and most suitable name for the part. A few of the terms are new, such being introduced only in those cases where a search of the literature failed to reveal a designation deemed proper for the part under consideration. Only one name was given to a part, and while the list may in no way be styled a new nomenclature, it has served to simplify anatom- ical terminology by greatly reducing the number of anatomical terms in current use. The reasons for undertaking a revision of anatomical nomenclature at the time Professor His brought the matter before the Anatomische Gesellschaft, most urgent. Hitherto, there had been no authentic principles governing the formation and usage of ana- tomical terms. With the rapid progress of the science of anatomy and the stimulation of research, in 318 1 ; i : i KliKXCi: IIAXDBOOK OF THE MEDICAL SCIENCES Anatnmir.il Nomenclature) the Basle ope and America, the reduplication of anatomical rune- had grow a excessive. The naming of a sti ure was left to tin- choice of the individual investi- 'ator, who was not infrequently ignorant of the work lone by his fellows in the same field. As a resull >ach teacher, each school, and each country acquired i peculiar group of anatomical names. These multiple is gradually found their way into tin- anatomical ext-books, each author adopting, or discarding whatever names he chose. One of the larger standard ol tin- era contained as many as 10,000 lames, over one-half of which were synonyms, while , , of the various synonyms employed in i number of standard works revealed a list of -ohm mii names. Indeed, for the approximately 500 >. a structures of the brain alone, Professor Wilder able to collect from the literature a list of no less ■ i mi names. This cumbersome multiplication of terms was a jriovous burden to both teacher and student, and rise to much ambiguity and confusion. The of double names for each pari in the schools was isl the rule. Such multiple synonyms as Valvula coli, vel ileocoecalis, vel Bauhini, vel Tulpi, vel ipii, wen' not infrequent. Anatomical termi- ■, was necessarily wholly lacking in uniformity and in any plan of construction. To usage alone left the final justification of a new term in the science. Important structures were differently named in the various countries, the Corpuscula lamellosa g known as the corpuscles of Vater in Germany and the corpuscles of Pacini in Italy. Xor, indeed, i his species of anatomical patois alone national in extent, but was characteristic of the various universities. Each great medical school had, in asure, its own anatomical language, and a student migrating from one university to another often forced to acquire a new set of anatom ical terms. I Ine of the first anatomists to revolt againstethe tyranny of multiple anatomical terms was J. Honle, who. in writing his well-known treatise on anatgmy, only one name for each part, relegatinfe all synonyms to the footnote. To his example Provissor His attributed his conception of an official reacsion of anatomical nomenclature. Henle further attacked the use of personal names in terminology and re- placed them by objective terms, on the ground hat- the use of such names frequently gave rise to this torical injustice. His efforts to simplify anatomical terminology, strangely, only tended to create still greater confusion, due to the fact that he himself introduced many new terms, and while his terminology found favor with many anatomists, others refused to pt it, and a third group became eclectic, reserving the right to retain the use of personal names. Individual endeavor, such as that of Henle, could not hope to effect a speedy reform in anatomical nomenclature, yet the efforts of a few pioneers paved the way for a concerted action on the part of the anatomical societies. Early in the nineteenth cen- tury John Barclay, Owen, and Pye-Smith began a crusade of reform in England, while later in America (1861) Dr. Leidy, the first president of the American Association of Anatomists, published a work on Human Anatomy, in which he eliminated all synonyms from the text, retaining only such terms, one for each Mire, as seemed most suitable. Numerous foot- notes supplied a list of synonyms. The use of proper names was also much restricted. Unfortunately his attempt to simplify American anatomical terminology met with little encouragement. A decade later Professor Wilder began to advocate a simplification of anatomical language and called attention to the special need of a revision of neurological nomencla- ture. Largely owing to his efforts, Committees on Anatomical Nomenclature had been appointed by the American Association for the Advancement of Science, the American Neurological Society, ami the American \ o ol Anatomists, prior to the adoption of the report of the German Commission. When the AnatOD chafl was founded at Leipzig, in 1887, one of the firsl matters discussed was the need of establishing a uniform nomenclal \ resolution was passed instructing the officers of the Society to undertake a revision of anatomical terms. However, a- soon as the task was begun. numerous unforeseen difficulties presented themselves and it at once became apparent that an undertaking involving so much detail would require the coopera- tion of many anat ists, and a period of se\ oral years, for its execution. At Berlin in 1889 His brought these difficulties before the ( lesellschafl and advocated the formation ol a permanent Commission on Nomen- clature with the appointment of an editor-in-chief, who might devote his time a! st exclusively for several year- to the work of revision. Hi- suggestions were adopted and the Commission was appointed with Professor v. Kolliker a- chairman and Professors 0. Hertwig, His. Kollmann, Merkel, Bardeleben, Toldt, Waldeyer, and Schwalbe as members. The two remaining need- of the Commission, viz., the securing of an editor-in-chief and the assurance of financial aid for carrying on the work, were quickly Professor W. Krause of Berlin accepted the post of editor. The expenses of the undertaking amounted to some 11,000 Marks, slightly in excess of the original modest estimate of 10,000 Marks. To defray this sum, the Anatomische Gesellschaft voted 3.S00 Marks, the balance being secured by grants from the scientific academies of Munich, Berlin, Leipzig, Vienna, and Budape-t. Before beginning their task the Commission wisely realized the necessity of limiting the scope of their undertaking. It was obvious that any attempt to establish a rigid terminology 7 for structures still the subject of dispute, could only end in failure. Accord- ingly the Commission decided to confine its work to the descriptive anatomy 7 of structures visible to the naked eye, or at least with the aid of a hand lens. The designating of the finer structures of microscopic anatomy was sedulously avoided. While the terms of the list were to be constructed in Latin, the Com- mission made it clear that anatomists, who might accept the terminology, should be left free to translate these terms into their native tongue. A further preliminary question of a delicate nature for the Commission to decide, was to what extent the nomenclature might assume an international charac- ter. The Commission attempted to establish clearly its position on this point. It was granted that the list was to be a product of the Anatomische Gesell- schaft, but as Professor His has stated, this Society, while founded in Berlin, from the first day of its origin, assumed a character broader than German. At the time of its organization a small majority 7 of its members were Germans (145), while the remaining members (129) came from Belgium, Denmark, Eng- land, Sweden. Russia, Austria, and France. The Commission reasoned that the composition of the Gesellschaft was sufficient cause for establishing an in- ternational standard of nomenclature. With this end in view, anatomical terms used in the standard text- books of anatomy 7 of countries other than Germany were considered in compiling the lists. Opportunely a meeting of the Anatomische Gesellschaft conjoint ly with the section of anatomy of the International Medical Congress at Berlin afforded the Commission a means of enlisting the services of such foreign anato- mists as Sir William Turner, Cunningham, Romiti. and Leboucq. At a later time Professor Thane of London was also included in the Commission. Amer- ica, it is true, was not represented on the Commission, nor were the representatives of France and England present at the signing of the report in 1895. Recogni- tion of the desirability 7 of imparting an international 319 Anatomical Nomenclature, the Basle REFERENCE HANDBOOK OF THE MEDICAL SCIENCES character to the -work of the Commission was acknowl- edged by the action of the Anatomical Society of Great Britain and Ireland in the appointment of a Committee in 1S93 to consider adapting the sugges- tions of the Commission to English needs, while from America, Professor Wilder had forwarded to the Commission a series of reports of Committees on Anatomical Nomenclature of the various scientific societies. In order to secure uniformity in the character of the revised nomenclature, the Commission formulated certain general rules, which they followed in the selection of anatomical terms. These fixed principles, as stated by the Editor, were: 1. Each part of the body shall have one Latin name; there shall be no synonyms separated by " sive" or "seu." Each nation using the Latin name may translate it in the way that seems best. 2. The name shall be as short and simple as pos- sible, and should recall some point of description, or distinctive character. 3. No part of the body shall have an unnecessarily long Latin name. 4. No two parts of the body shall have the same name unless they are truly homologous structures. 5. The names shall be consistent with Latin gram- mar and orthography. 6. Personal names shall, as far as possible, be re- moved from anatomical terms, except where they actually mark historical observation. 7. In the whole work the Commission shall endeavor to be as conservative as possible. 8. The same names shall be used for arteries, veins, and nerves, where they run together; e.g. A. fem- oralis, V. femoralis, N. femoralis. 9. The same names shall be given to foramina and to the vessels and other structures which pass through them. 10. Adjectives shall, as far as possible, be used as opposites; e.g. profundus and superficialis. 11. Ligaments shall be named according to their attachments, the final part of the name indicating the proximal attachment; e.g. sacroiliac, not, iliosacral. 12. There shall be no hybrid names. While the Commission followed these guiding prin- ciples as closely as possible, in certain instances, a deviation from the rules in the selection of a term seemed advisable. Thus, while such cumbersome terms as M. petrosalpingostaphylinus could read- ily be discarded, no good substitute could be found for so commonly a used term as M. sternocleido- mastoideus. In a few instances dual terms were retained, as in the case of Valvula bicuspidalis ve] mitralis, the latter term being retained out of eon- cession to the clinicians. Nor did it seem wise in every case to affix similar terms to neighborhood structures, such a term as Foramen spinosum being retained as being preferable to styling it Foramen meningeum medium by virtue of its penetration by the A. meningea media. A systematic plan for the execution of the work to which the Commission adhered during the early years of the work, was elaborated by the Editor and sanc- tioned by the Commission. He suggested a compila- tion of the lisl of anatomical terms used in a stand- ard text-book of Anatomy (Gegenbauer's "Lehrbueh der Anatomie des Menschen" being so employed). These terms were arranged in vertical columns, while parallel to them, in other columns, were placed the various synonyms from a number of other widely used text-books of anatomy. A copy of this list compiled by the Editor was sent to each member of the Commission, with a request that he indicate the term of his choice for the part, from one of the syno- nyms submitted, or in case none of the terms seemed suitable for the part, that he propose a new name. The lists, along with comments upon the terms, were then returned to the Editor. Following this plan, the terms of Myology were first subjected to the ballot. The result of the first vote was most gratifying to the Commissioners, since eighty-five per cent, of the terms considered received a majority vote, and of this number, more than forty percent, received an almost unanimous approval. A second revised list was issued, containing the selected terras and those still in dispute, together with the new- names proposed by the members and comments thereon. Whatever terms the second written bal- lot left undecided, were finally adjusted in personal meetings of the Commission. The fact that such meetings of the Nomenclature Commission were held during the annual session of the Anatomische Gesellschaft afforded the Commission an opportunity of seeking the advice of the distinguished members of that bod} T . In such manner the terminologv of Myology was completed at Munich in 1S91 with a list of 300 accepted terms. At a later session in Vienna the terms for Osteology and Angiology were similarly brought to completion. As the process of balloting by correspondence for the proper terms of the list progressed, it became evident that a repeated voting over terms in dispute gave no more satisfactory results than a single ballot. Frequently it happened that newly proposed names, representing the fruit of much thought and special knowledge, received too scanty consideration, and were rejected without sufficient testing. In order to obviate this fault, the Commission, somewhat hastily, decided that all new terms and comments should be considered in verbal discussion. This scheme, however, proved to be wholly impracticable, owing to the tedious discussions provoked. As a wise alternative it was resolved to allot the work under certain headings, in charge of special commit- tees. At Vienna a committee, consisting of Profess- ors Merkel, Thane, and Toldt, was appointed to take charge of Angiology. At a later time Profess- ors Rudinger, Toldt, and Merkel were assigned to regional Anatom}', and Professor Toldt was appointed a committee of one in charge of Syndesmology. The need of correlation of the work of these special committees next forced itself upon the Commission. Since the balloting for the terms had taken place at different times, and frequently at long intervals, a certain element of dissimilarity, and in a few instances, contradictory expressions, had crept into the lists. In order to adjust these difficulties and to impart uniformity and logical sequence to the nomencla- ture, a general editing Committee composed of Pro- fessors Hi-. Krause, and Waldeyer was appointed. This Committee soon found its task of smoothing out inequalities and correcting contradictions a most arduous one, working continuously for three years partly by correspondence, and partly by per- sonal interviews. Frequently authorities were con- sulted in order to arrive at clearness and unity in regard to disputed and difficult points in terminol- ogy. The most perplexing sections of the work proved to be Neurology and Splanchnology. With the appointment of a general editing Committee its original plan of execution was somewhat altered, and the work much facilitated. The individual mem- bers of the Commission were invited to forward their various suggestions and comments for the terms of the sections under discussion, prior to the first ('al- lot, in order that such suggestions might receive due consideration before the voting. After the vote was taken, the lists were rearranged by the editor and sub- mitted to the general editing Committee. In this way the value and precise meaning of each express ion was subjected to critical examination. In many instances the bibliography was consulted and dissec- tions undertaken, to verify the fitness of the decli- nations for structures in question. The lists, thus revised, were again submitted to the members of the Commission for approbation, or further comments, 320 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anatomical Nomenclature, the Basle which in turn received the consideration of the edit- ing Committee. The final revision of the various chapters was sent to the members of the Commission in July, 1894. This revised list was again critically studied and tested by the members. After a care- ful consideration of the comments and suggestions arising from this examination the definitive lis! of anatomical terms was presented to the Anatomische Cesellschaft as a whole, for adoption, during the jion at Basle, 1895. The task of sweeping out of anatomical terminology tic great ma" of synonyms, which usage had well established, was one that presented many difficul- ties. One of the greatest of these was in respect to the use of personal names as designations for structures. The question of eliminating these from the nomenclature was very carefully weighed by the Commission. Many convincing reasons were urged by Professor His against their retention. It was stated that the use of personal names frequently rise to historical injustice, the name applied to a structure not being that of the real discoverer, hut of some later observer. Personal names of dif- it anatomists in two or more countries were frequently chosen for the same structures, the glands of bieberkuhn in Germany being those of Galeati in Italy. Moreover, no system had been followed in I he choice of names of the old anatomists. The names of such famous anatomists as Harvey and Vesalius were wanting in anatomical literature, while the names of Malpighius and Eustachius had been duplicated. A more cogent reason for dropping personal names was found in the fact that a great mass of proper names had accumulated in modern anatomical writings, especially in the literature of the specialties, where frequently names of very questionable scien- tific importance were encountered. On the other hand, in favor of the retention of personal names in the lists, Professor His pointed out that the use of such names may at times furnish good mnemotechnic material. It was believed that the use of such terms as Poupart's, Gimbernat's and is's ligaments might incite a student to acquire the meaning of such expressions, whereas his interest in a Ligamentum inguinale, L. lacunare, or L. ingui- nale rcflexum, was apt to be less certain. Again the members of the Commission were dominated by a cer- tain feeling of piety, which inhibited them from drop- ping personal names. It was a question in their minds whether names of the immortals, which for centuries had served a good and useful purpose in anatomical literature, should be sacrificed for a prin- ciple. Moreover, it was doubtless advantageous for the student in his first semester to encounter such names as Fallopius, Eustachius, and Malpighius, for thereby a _ certain historical interest was aroused which is stimulating. As a solution of this perplexing question, the Commission, very wisely it seems, effected a com- promise in place of arbitrarily banishing all personal names from the lists. For each structure a material objective designation was given, and the better known personal names were added in brackets. Following the precedent of the Zoological Nomenclature Com- mission, such names were put in the genitive case. Further, the use of personal names was much cur- tailed, being retained only where these were common to a majority of the national anatomical terminol- ogies. This mode of treatment, while less simple than the use of material terms alone, offered the advantage of leaving to time the final decision as to which of the two terms would survive. Another problem which confronted the Commis- sion was the need of incorporating the terminology of the medical specialties into their list. The many- specialists, who had carried on investigations in their own special fields, notably in Neurology, Otology, Vol. I.— 21 Ophthalmology, and Laryngology had introduced itito the literature an anatomical nomenclature whirl, deviated greatly from the terms used in tin' stand- ard text-books. A danger had arisen of a veritable terminological crevice. The question arose should the ( lommission adhere to the old plan, or should eon- cessions be made to tin' specialists.' Careful consid- eration of the matter convinced the members of the Commission that the nomenclature of the special- i-t - had arisen through a real need of the same, the terms of the text-books being no longer adequate. It was clearly the duty of the Commission i" aco pt the terms of the specialists, or to supply better ones. A conference was held with a number of the lead- ing specialists, active as investigators, and a mutual adjustment was effected w hereby a full list of the names of macroscopic structures in these special regions was to be included in the nomenclature. In return the Commission was assured that the nomen- clature of the Anatomische Gesellschaft would be accepteil as soon as it covered the requirements of the specialties. In the course of selecting the list of terms from the text-books, the Commission encountered many antiquated and obscure names, some of which \ used by one author in a sense different from that of another, owing, in certain cases at least, to obscure or inexact views. The fact was revealed in the dis- cussions that the members of the Commission them- selves were frequently at variance regarding the pre- cise meaning of an expression. In the case of such ambiguous terms there arose the need of searching the bibliography, making dissections, and in a few instances undertaking research, over a given term. Such investigations led to the introduction of a num- ber of new terms into the lists, where these were demanded for the sake of clarity and accuracy. Pro- fessor His and his colleagues have written explanatory notes indicating the sense in which these new terms were employed, such notes being inserted at the end of the list of terms in the official publication of the BNA. With the completion of the work of the Commission, representing six consecutive years of arduous appli- cation to their task, the final report was officially presented to the Anatomische Gesellschaft by Pro- fessor His at Basle, 1895. The report was unani- mously adopted by the Gesellschaft. In presenting their report the Commissioners emphasized the fact that they regarded their list as only provisional, and by no means complete. There remained an undoubted need of a revision of certain gaps in the lists. Their aim had been to prepare a common teaching nomenclature, and at the same time to create a uniform standard, which might serve for use in anatomical literature, especially that of an international character. Professor Waldeyer, in his presidential address at the following meeting of the Gesellschaft, invited his colleagues to point out errors and defects in the lists along with suggestions for improvement and referred to the advisability of having separate sections of the nomenclature taken up by the Commission for revision. The BNA nomenclature may now be justly re- garded as the standard of anatomical terminology in the leading anatomical laboratories of the world. The official list was published not only in the anatomical journals, but also separately by Professors Krause and His, in the form of hand-books containing the list of terms with explanatory notes. The appear- ance of such widely used atlases as those of Spalte- holz, Toldt, and Sobotta couched in the BNA terms, shortly following the report of the Commission, ensured at once its use in the leading German uni- versities. Nor was its recognition in foreign coun- tries long deferred. The Anatomical Society of Great Britain and Ireland appointed a Committee in 1893 to consider the adaptation of this nomenclature 321 Anatomical Nomenclature, the Basle REFERENCE HANDBOOK OF THE MEDICAL SCIENCES to the needs <>f English anatomists. Professor Cun- ningham introduced the BNA terms in the first edition of his text-book, published in 1902, adding separately a glossary of the terms. In America in 1898 the Committee on Anatomical Nomenclature of the American Association of Anatomists gave an official recognition of the BNA terminology by a recommendation of the use of many of its terms, the Committee, however, in respect of many terms, pre- ferring mononyms, as suggested by Professor Wilder, in place of the less simple dionyms of the BNA list. At a later time Professor Barker in his translation of Spalteholz's Atlas, rendered the complete list of the BNA available for students and teachers, while in a monograph on Anatomical Terminology with special reference to the BNA, published in 1907, he made a strong plea for the adoption of the nomen- clature in its entirety in America. Gradually a ma- jority of the authors of the leading American anatom- ical text-books have come to employ the BNA terminology, either exclusively or in part, some of the authors preferring the anglicized forms, while others append the Latin terms in brackets. The Commission has rendered an invaluable serv- ice to medical science in establishing an international code of anatomical terminology and in abolishing a mass of needless terms. The use of the nomenclature in anatomical journals has greatly facilitated the reading of articles published in a foreign country. It was acknowledged by the Commission that the terms of research lay wholly beyond their province, and the right of the investigator to apply special names to parts which have no designations was fully recognized. Their aim had been to prepare a common school speech, free from ambiguous expres- sions, realizing that research requires a terminology of its own, which lias no pretension of coming into school usage. As a result of their efforts the work of the student has been reduced by at least one-half with a sparing of the memorizing of over 5,000 names during his anatomical studies. A further result, of great importance, achieved through the labors of the Commission, was the establishment of certain principles regarding the formation and use of anatom- ical terms, which will tend to impart uniformity and simplicity to anatomical terminology, and which may serve as a basis for future revisions of the same. Although the advantages to be gained by the adop- tion of a uniform standard of terminology were read- ily conceded, it was nevertheless to be expected that for a time a certain strife must exist between the use of the older terminologies and the BNA list. The Commission was fully aware of the impossibility of forcing any fixed nomenclature, however superior, either on teacher or pupil, believing that its adoption must be a matter of gradual growth dependent on its intrinsic merits. Indeed, among the Commis- sioners themselves, it was questioned whether a rigid terminology might not act as a stumbling block and retard the progress of research. In order to enlist the good will and cooperation of anatomists generally in accepting the list, they carefully re- frained from giving names to structures still under investigation. Despite the care exercised by the Commission there has crept into the lists a number of defects and errors, which have evoked lively criticism, and have given rise, in certain quarters, to objections, which have served to retard in some measure a uni- versal acceptance of the nomenclature. Some of the objections urged have arisen through a misconception of the intention of the Commission. The fact that it has been erroneously styled a new terminology, has im- peded its adoption on the part of clinicians who have acquired their anatomical terms from the older text- books. Yet, as a matter of fact over ninety per cent, of the terms are already familiar to English-speaking anatomists, and in the few instances where new terms have been introduced these are, in much the greater ma- jority of cases, preferable to the older terms. Another misapprehension, which has deterred many from using the BNA list, is the false impression that the Latin names, as constructed in the lists, were to be used as such in every day speech. This was clearly not the purpose of the Commission, it being intended that the anatomists of the various countries, would in spoken language, translate the terms into their native tongue. The fact that the BNA terms more closely resemble the corresponding English names than those of any other language, should render them readily acceptable to English-speaking anatomists. It has been urged with some degree of justice that the BNA terms do not always afford the simplest form possible. In numerous instances dionyms have, been used where mononyms would seem to suffice. The use of polynyms had already grown burdensome to both student and clinician and the tendency, in daily speech, had been to discard the use of such in favor of mononyms. Thus one commonly hears cecum in place of the official Caput ccecum coli, and cortex rather than Substantia corticalis, while the popular term appendix would seem preferable to the more authentic Processus vermiformis. The nomen- clature Committee of the American Association of Anatomists have recommended the use of mononyms, in many instances, as substitutes for the more cumber- some dionyms of the BNA list. In defense of the attitude of the Commission on this point, it may be said that a desire to avoid ambiguity restrained them from selecting the simplest term in many cases. Moreover, it was shown that the free use of mononj'ms would require the coining of many new terms, and the creation of etymological barbarisms. Following the critical examination to which the nomenclature has been subjected since its publication, it is not surprising that a few inconsistencies, and inappropriate expressions, have been demonstrated. The Commission has been accused of deviating from the principles laid down in the selection of terms, in the introduction of new, or comparatively unfamilar names for structures, where the older terms would seem preferable, notably in the case of the names given to several of the carpal bones. It was obviously inconsistent that, while the term maxilla was applied to the upper jaw and mandibula to the lower, the name Glandula submaxillaris should be retained. The, term Bursa mucosa has been pointed out as a misnomer, since the secretion of a bursa is not mucus, and Bursa synovialis or serosa lias been proposed as more ap- propriate. Again the Commission has been charged with violating the rules that "each term in Latin shall be philologically correct." Triepel and others have pointed out numerous etymological defects in the terminology, and a proposed etymological reform of the entire list, employing only classical Latin and latinized Greek expressions, has been instituted by Triepel. The introduction of many hybrid names into the lists has been criticized, although it is admitted by the critics that there is a certain justification for the use of such hybrid terms as urethralis in place of the more correct urethricus on the ground of euphony. Again it may be grammatically proper, but whether preferable or not, seems doubtful, to use carpiaeus, or carpicus, for carpeus, and coccygicus for coccygcus. It has been stated with respect to certain adjectives in the list ending in -icalis that there is correctly no such termination and that such terms as A. umbilicalis and M. lumbricalis should be A. umbilicaris and M. lumbricosus. Another defect is the undifferentiated use of the ending -ideus. A number of anatomists hold the opinion that the ending -ides for the Greek ending -sidris should remain in anatomical ter- minology, the term Os hyoides being preferable to the BNA term Os hyoideum. Some would prefer the writing of anulus in place of the less correct annulus, while the term antibrachium should be more properly written antebrachium. 322 Kl I IMM.XCK HANDBOOK OF THE MEDICAL SCIENCES Anatomy, History of It [a admitted that the UNA nomenclature does ,,,,t tneel the need of comparative anatomy. Most of the expressions, especially those for muscles been constructed in application to human anatomy and hence are misleading for vertebrate anatomy. Thus the use of the terms M. pectoralis major a minor would be erroneous if applied to the relative proportions of those muscles in the vertebrates, in, from the view point of morphology, the BNA grouping is at times quite artificial. As pointed out Professor McMurrich certain of the facial muscle: have been grouped as a M. quadrants labii superioris credited with three heads of origin, which have elsewhere been more properly regarded as distinct muscles. A revision of the BNA list to render it applicable to vertebrate anatomy is highly desirable. The appointment of an International Commission on logical Nomenclature has already proven a rec- ognition of this need. There has been, it is stated, a certain reluctance on the part of some American ami English anatomists ept the BNA nomenclature, for the reason that it is the product of a German organization, and uch is not adapted to the needs of English- ting anatomists. However, as has already been pointed out, the Anatomische Gesellschaft might fairly claim to be international in its composition and the Nomenclature Commission embraced representa- tives from several countries. America was not represented on the Commission, doubtless due to the that anatomical laboratories had not yet attained a high degree of organization, and but few American anatomists attended the meetings of the Gesellschaft at the time of the formation of the Commission. In the various international nomenclature committees which have been formed since then, American anat- omists have obtained full representation. Moreover, in defense of the initiative taken by Germany in under- taking a revision of terminology of an international character, it would seem probable that at the time the reform was instituted, no other country could have provided so distinguished a group of anatomists, who might devote so much of their time for so long a period to the undertaking. The scientific world. which recognizes no national boundaries is under great obligation to the Anatomische Gesellschaft for initiating terminological reform, and even should the nomenclature established by it not prove the ideal one, the obvious benefits gained for anatomical science through the general adoption of it as the international terminology, would seem to offset any sacrifices attendant upon the relinquishing of a few- national colloquialisms. The ultimate result of the efforts of the Anatomische llschaft toward terminological reform has been broader in extent than the mere production of the BNA nomenclature. The BNA list of terms has been welcomed by anatomists as providing the best common anatomical terminology yet presented. Further than this the work of the Commission estab- lished a basis for future and more comprehensive revisions of anatomical terms. Since the presenta- tion of the Basle report a number of Nomenclature Committees of truly international character have been formed. Some years ago an International Com- mittee was appointed to revise Myological Nomencla- ture, with a view of coordinating, if possible, the comparative and human anatomical terminologies. Professors McMurrich and Harrison were made the American representatives. As yet no report of the Committee has appeared. At the third meeting of the Commissionfor Brain Investigation, appointed by the International Association of Academies, at Vienna. 1906, a committee for the revision of neurological nomenclature was formed, with Professor Waldeyer as chairman. During the second International Congress of Anatomists at Brussels, 1910, Professor Minot, on behalf of the American Association of Anatomists, presented a recommendation for the formation of an International Committee to revise embryological nomenclature and prepare a li-t of standard terms. Pi M chairman) and Mall represented America on the I ommittee. With the cooperation of these various nomenclature com- mittees, revising and elaborating the work of the B Commission as they will, the establishment of a uniform international standard of terminology for tin' various anatomical would seem ftdly assured. Benson Amhkose Cohoe. BlBLIOGRAPHT. Annahme der Nomenklatur durch dii '-haft. Anat. Ariz., Bd. X.. Erganz., S. L61, 1895 v. Bardeleben, K.: Einige Vorschlage zur Nomenklatur. Anat. Am., D.I. xxiv., S. 301-304, L904 Barker, L. F.: Anatomical Terminology with Special Reference t.. the UNA. Blakiston, Phila., L907. Chaine, J.: Reforme de la nomenclature myologique. Anat. Any, , Bd, xxvii., Erganz.. S. 38-39, ton.-,. genbauer, C.: Bemerkungcn zur anatomiechen Nomen- klatur. Morphol. Jarhbuch, Bd. XV., S. 151, 1S98. Bis, W.: Die anatomische Nomenklatur. Nomina anatomica. (Reprinted from the Arch, f. Anat. u. Physiol., Anat. Abth., Leipzig, 1895. Supplement-Band.) Krause, \V.: -Die anatomische Nomenklatur. Internat. Mo- natsschr. f. Anat. u. Physiol., Bd. jr., S. 313, 1893. Spitzka, E. A : Review of Dr. Barker's Book. Bulletin of the Johns Hopkins Hospital, Vol. xviii.. No. 195, 1907. Triepel, H.: Die anatomischen Nanien, ihre Ableitung u. iche. 2 aufl. Wiesbaden. 190S. Triepel, H.: Die anatomische Nomenklatur. Ergebn. d. Anat. u. Entwickl., Bd. xvii., S. 531-554, 1909. Triepel, H.: Nomina anatomica mit Unterstutzung von Fach- philologen bearbeitet. Wiesbaden, 1910. Triepel, H. : Merkblatter zur anatomischen Nomenklatur. Anat., Anz., Bd. xxxviii., S. 161-165, 1911. Yiorordt, H. : Bemerkungen zu BNA. Anat. Anz., Bd. xiii., S. 1S1-1S3, 1S97. Waldeyer, W.: Eroffungsrede, 11 Vers. d. Anat. Gesell., Anat. Anz., Bd. xiii., S. 2-3. 1S97. Wilder, B. G.: The Fundamental Principles of Anatomical Terminology. Med. News, Phila., Dec. 19, 1S91. Wilder, B. G.: Some Misapprehensions as to the Simplified Nomenclature of Anatomy. Proc. of the Amer. Assoc, of Anat., X. Y . 1895, pp. 35-39. Report of the Majority of the Committee on Anatomical Nomen- clature. Proc. of the Amer. Assoc, of Anat., 11th session, N. Y., 1S9S. Anatomy, History of. — Considering the necessity of the anatomical sciences as a basis for the proper study of the healing art, and the high position assigned them in modern times, it may seem strange that their early development was slow, and the knowledge of the ancients concerning the structure of the human body crude and superficial. The principal cause of this was the prevalence of animistic ideas, it being thought that extraneous spirits inhabited or controlled the body in some mysterious way. Involuntary movements, such as the pulsation of the heart and arteries, the twitching of muscles, the phenomena of respiration and bodily heat, were all considered indubitable signs of the presence of such spirits, to which were ascribed most cases of disease and disordered action. After leaving the body the psychical entity that ani- mated it was thought to maintain some occult relation to it; hence the corporeal remains were either preserved with pious care, or burned or entombed to prevent their suffering insult or injury that might affect the career of the spirit in the other world. Mingled with these superstitious ideas were others derived from horror of death and repulsion from corrupting flesh. Contact with a dead body was usually held to be a defilement requiring long purification, and to attempt to in- spect its internal structure was a sacrilege meriting the severest punishment. Dissection was, under such circumstances, practically impossible. It is certain that but few writers of antiquity were able to avail themselves of this method of research. The sources of information were therefore indirect. 323 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Animals killed either for food or sacrifice, the occasional examination of persons severely wounded or suffering from eroding diseases, the noting of the effects of putre- faction which displayed the deeper structures, es- pecially the bones, were the usual means employed for the investigation of the human body. In Egypt, it is true, bodies were eviscerated for the purpose of preserving them as mummies; but this appears to have been done by a low class of servants under the direction of priests who regarded the interests of the spirit in the other world as the only essential, and who therefore gave no thought to exact anatomical knowledge. Yet among the ancient Egyptians are found some of the earliest attempts at recording anatomical data. They were acquainted with the heart, the lymphatic glands and the crystalline lens. The Ebers papyrus, of about 1550 B.C., and said to be the oldest complete book extant, relates to the healing art and contains incidental allusion to the structure of the body. Vessels and nerves are together des- ignated as "metu"; of which four are distributed to the nostrils, four to the temples, four. to the head, two in each hand and foot, etc. The heart is regarded as the center of the vascular system, and vessels con- taining blood, air, water and other fluids pass from it to all parts of the body. Vital spirits are said to enter one nostril and penetrate to the heart; an idea which was to have a great effect upon anatomy and physiology as far down as the seventeenth century. Similar determinations, of no greater value, are found in papyri of a somewhat later date. Contemporary with the Egyptian culture, or possibly anterior to it, was that of Chaldaea and Assyria from which the Phoenicians and Hebrews derived much. One of the contributors to the Ebers papyrus is stated to be from Byblus, a town of Phoenicia. Certain cuneiform inscriptions indicate that the situation of the vessels of the neck was known, as they describe the compression of these structures to relieve the pains of circumcision. These inscrip- tions refer to the heart as the seat of the mind, the liver as the central organ for the blood. The anatomy of the Hebrews was probably derived mainly from Chaldean, Assyrian, and Egyptian sources. The principle of life was by them believed to reside in the blood (Gen. ix. 4; Lev. xvii. 11), which was accordingly forbidden as food and used as a pro- pitiatory offering. The heart was supposed to be the seat of the understanding, courage, and love; to dilate with joy, contract with sadness, harden or soften with the passions. These expressions, which have become wholly figurative in modern times, were formerly believed to be literally true. The later Talmudists had some anatomical knowledge of the female geni- talia, the oesophagus, the lungs, the kidneys, the spinal cord, and the cauda equina. One of the rabbis, at the close of the first century, is said to have boiled a body for the purpose of obtaining the skeleton. A fabulous bone, "luz," was thought to become the seed of the body from which it is to be renewed at the resurrection. The early writings of India contain no anatomical knowledge except names of a few parts of the body. Somewhat later (900-200 b.c.) there are rude attempts at the enumeration of structures. To what extent these enumerations are based upon actual examina- tion and misinterpretation of anatomical facts it is impossible to say. In them the primitive elements of the body are air, bile, and phlegm, air having its seat below the navel, the bile between the navel and the heart, the phlegm above the heart. Seven organic products were believed to be formed from these primitive elements: watery chyle which in the liver and spleen forms blood, from which arises flesh which forms cellular tissue, from whence comes bone which generates marrow, which gives origin to semen and menstrual blood. The ancient Hindoos are 324 said to have practised dissection, it being held lawful to pursue such investigations for scientific purposes though under many limitations and restrictions; but the sculptures of the rock-cut temples of Elephanta and Ellora show ignorance of the anatomy of muscles. Later authors appear to have had a vague idea of the circulation of the blood, as they state that the watery chyle circulates through the vessels and irrigates the system as water does a field. The Chinese have not, even at the present day, any exact anatomical knowledge. The tracing of their crude notions back to the mists of the past is of purely archeologic interest, and it is difficult to say whether the alleged great antiquity of some of their medical writings is based upon authentic facts. They considered the elements of the body to be air, water, "metal," and "wood"; the liver to be the seat of the intelligence, the seat of life to be in the middle of the breast. Arteries and veins were not separately distinguished, but some notion of a circulation or translation of the blood appears to have been ad- vanced, as it is stated that it completes a course throughout the body fifty times in twenty-four hours. In rare instances only was dissection allowed. It is alleged that in the fourth century a.d. forty corpses of decapitated persons were turned over to phy- sicians for dissection, and that in the eighteenth century the emperor Khang-hi, inspired by the Jesuit fathers, had the anatomical works of Dionis and ThomasBartholin translated into Chinese. The Japanese in matters of anatomy copied from the Chinese. Their older writings are curious mixtures of fact and error. They teach that the heart contains blood, rules all the other viscera, and is connected with the liver, lungs, spleen, and kidneys; that blood is prepared in three "combustion organs" of rather mythical character, perhaps the thoracic duct, the pancreas, and the lacteals. They assert the structure of the lungs to be like that of a honeycomb, and state that they contain a nourishing gas which penetrate the whole body outside the vessels that carry the blood. The brain, the spinal cord, and the marrow are said to be of one nature, the brain having the highest rank. The seat of the soul is stated by most authors to be the heart, as it has been seen in some animals to beat after the severing of the head from the body. Others place it in the brain, the spleen, the lungs, the kidneys, or the liver. The nerves are often confounded with the tendons, often described as tubular canals. In the middle of the eighteenth century, a physician named Yamawaki obtained per- mission from his prince to dissect a body, an illegal act that could be done only under powerful protection. He published his observations and declared that the older teaching should no longer be thoughtlessly followed. Dissection was thereafter surreptitiously practised, and very accurate wooden models of the skeleton were made. About 1775 the Dutch edition of an anatomical work by Kulmus, Professor at Dantzig, was translated into Japanese. It is among the Greeks that we first meet with a knowledge of anatomy that can be called scientific. With keen and active intelligence they examined and speculated upon all things in the world around them. Prepossessed with the anthropocentric theory of the universe, they attained only a partial and distorted view of natural phenomena, but often showed aston- ishing powers of generalization in speculative theories. Among them arose the group of so-called "natural philosophers," at the head of whom we find Pytha- goras (584-504 B.C.). He attempted to explain natural phenomena by means of harmonic numbers which he considered as actual entities having myste- rious powers, the elements of the body being comprised in the number 10, each single number (1+2+3+4) having therein a counterpart. He was the first to deny the spontaneous generation of animals, holding that all life must spring from germs preexisting in the REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anatomy! History of semen which, formed from the brain of the male, combines with moisture from the brain of the female, Ml | is t In' perfected foam of (he blood. This idea is perhaps connected with thai of the origin of the god- dess of generation, Aphrodite (aas' work into Latin, by Constantinus Afer, a Benedictine monk {circa 1080), is probably the work on anatomy in that Language (Hyrtl). The leavening influence of the crusades now began to be felt. The uniting of the scattered peoples of Western Europe into vast armies that made long journeys by land and sea, and came in contact with nations of totally different culture and habits of thought, had great effect in c billing the small, warring, feudal factions into larger social units more susceptible of advancement, in opening new avenues of com rce, in diffusing a knowledge of t he learning of the East, and in bringing about a revival of intel- lectual activity. New universities were founded throughout Europe; at Bologna in 11 10, at Padua in 1228, at Salamanca in 123'.), at the Sorbonne in 1253. Others whose foundations dated back to the Roman period received new accessions. Among the latter were Salerno and Montpellier, at each of which an active medical school was established. At Salerno was seen the first symptom of a revival of practical anatomy, for the Emperor Frederick II. (1212-12.">(l) made a law in 1240 that no one should practise surgery without having been previously examined in anatomy, and provided that a dissection of the human body should be made at Salerno once every five years, inviting physicians and surgeons from all parts of the empire to witness it. It has been erroneously stated that the bull, dc sepulturis, of Pope Boniface, issued in 1300, was an interdict against dissection; but it was really intended to prevent the gruesome practice of dismembering and boiling dead crusaders, "more teutonico," for the purpose of more easily transporting their bones to their native land. The bodies of the Emperor Barbarossa, of Saint Louis (King Louis XL of France), and of many nobles were treated in this manner. The Senate of Venice, in 1308, decreed that a human body should be dissected annually. It is uncertain to what extent these dissections were carried, but it is prob- able that only the larger viscera were examined. Among the products of the school of Salerno that have survived are the "Anatome Porci" of Copho, and the anonymous "Demonstratio Anatomica." These are both based wholly upon dissection of animals. There is evidence that at this period autopsies were occasionally held to determine the cause of death, whether by poisoning or otherwise. It is also said that the bodies of those who had been hanged were, in Italy, not infrequently given over to physicians for dissection. Occasionally bodies were stolen for anatomical purposes. It is at about this time that occurred the first attempts at pictorial representations of bodily structure. These are found in a translation of Galen made by Nicholas Regio and published at Dresden in the fourteenth century. Two manuscripts on anatomy by Mondeville and Magister Ricardus that have survived from the school of Montpellier also contain rude drawings of structures. The credit of first establishing systematic public demonstrations of anatomy belongs undoubtedly to Mundinus (Raimondo de Luzzi, Mondino, 1275-1326), who taught at Bologna. Not content with expound- ing Galen, Abbas, and Avicenna, he brought the science back to the correct path of ocular investiga- tion. At least three bodies of women were publicly dissected by him, and there is reason to believe that the number was considerably greater. He is the author of a small work known as the "Anathomia 327 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Mundini," that was circulated extensively in manu- script before the invention of printing, and afterward ran through at least twenty-three editions. Although very incomplete and containing numerous errors, it was used as a text-book for two hundred years. It is very difficult to read, as much of the nomenclature is borrowed directly from Arabian authors. The abdomen appears as the "myrach," the peritoneum the "cyphach," the omentum the "zirbus," the sternum "the shield of the mouth of the stomach." Some of his appellations are still used: as "nucha" for the nape of the neck, "saphena" for the great superficial vein of the thigh. His anatomy is crude and incomplete rather than positively erroneous. He held that the body has three cavities (ventres): the head, containing animal members; the thorax, spiritual members; the abdomen, natural members. His anatomy of the heart and of the pulmonary circulation is fairly accurate as he follows Galen. In view of the imperfect and incomplete character of this treatise of Mundinus, it is difficult to under- stand its great influence upon the anatomical instruc- tion of that age. It was, however, the first work since Galen avowedly based upon personal inspection of the human body, and it appealed to the medieval spirit of curiosity that now began to manifest itself. The same impulses that led Marco Polo to the terri- tories of the Great Khan and impelled the alchemists to new discoveries in their search for the transmuta- tion of metals, animated many physicians of that time in their examination of the body of man. A zeal for anatomical studies arose, first in the Italian, afterward in the French and German universities. At Mundinus' own university of Bologna definite rules for dissection were established. At Venice (1308), Florence_(13S8), Padua (1429), also at Ferrara and Pisa dissection was either required or allowed as an aid to medical instruction. Pope Clement VII (1523-24) granted it at Rome. At Montpellier in 1376 or 1377 the medical faculty obtained from the Duke of Anjou a regular license to dissect the cadavers of criminals, which was successivelv continued by the kings of France (Charles VI., 1396; Charles VIII., 1496). In Prague dissection was practised from the very foundation of the university in 134S, and a building was given for that special purpose in 1460. At Vienna dissection was practised as early as 1404, and made a definite part of the medical curriculum in 1433. Pope Sixtus IV. granted special authority for dissections at Wittenberg in 14.82 and it was practised at Tubingen in 1485. The first anatomy act in England was passed in 1540, allowing the company of barbers and surgeons of London four bodies annually for dissection. In Paris we hear of it as early as 1478 and Moreau says it was customary to make four dissections annually. In 1483 the Paris Faculty decreed that graduates in medicine should be required to have anatomical knowledge. No doubt the actual number of dissections was greater than is shown by these scattered records. Yet this was nowhere carried on with the care and precision that characterize work in modern schools. The freeing of muscles, vessels, and nerves from the tissues that envelop them seems not to have been understood. Usually the great cavities of the body were opened and the principal viscera therein con- tained were displayed and demonstrated. Slices were removed from the cadaver by a razor in the hands of an attendant. The modern methods of injection and preservation were, of course, unknown; and a cadaver was soon a mass of disgusting and noxious putrescence. There was as yet no approach to exact and complete anatomical investigation. That anatomy was but of slight assistance to either medicine or surgery is amply shown by the records of the time. Indeed, it fell into such disrepute that Paracelsus (Theophrastus Bombastus von Hohenheim, 1 193-1541) declared it to be useless to know the internal structure of the body, that a knowledge of the shape or situation of the lungs, heart, or stomach was of no value in the diagnosis or treatment of dis- ease. In 1525 he burned the works of Galen and Avicenna before his pupils at Basle, denouncing these teachers as blind guides. This was at the close of an address in which he denounced scholasticism which he felt was retarding the progress of true science. He said "I would admonish you to put aside for awhile the mere dreams and opinions of others who think by rote and not by experience. Of what use is the rain that fell a thousand years ago? We are more interested in that which falls to-day." Some of the doctrines of Paracelsus reappear at later periods. He considered the body to be a microcosm representing the entire external universe, formed from preexisting and indestructible germs (Weis- mann's germ plasm), and governed by astrological influences, the sun affecting the heart, the moon the brain, Mercury the liver, etc., etc. The functions of the body he supposed to be carried on by the archcens, a sort of dcus in machina, that resided in the belly. He made many other fantastic specula- tions, especially in therapeutics and appears to be the original author of the homeopathic doctrine of " like cures like." Among those who carried on the work started by Mundinus and somewhat extended the domain of anatomy are: Gabriele de Zerbi (1468-1505), professor at Padua, Bologna, and Rome, who first separated the organs into systems, described the musculature of the stomach, and the puncta lachrymalia. He knew that the tunica vaginalis testis is derived from the peritoneum. Achillinus (Alessandro Achillini, 1463-1512), pro- fessor at Bologna and Padua, author of a commentary on Mundinus, who discovered the malleus and the incus, the labyrinth of the ear, the patheticus nerve, the ileocecal valve, and the entrance of the bile duct into the duodenum. Alessandro Benedetti (1460-1525), professor at Padua in 1490, afterward at Venice, built the first anatomical amphitheater. His demonstrations were public and he complains of the "numerous populace" that crowded to them. He wrote a work on anatomy that is one of the very best of the period. Berengarius Carpensis (Jacopo Berengario Carpi, 1470-1530), professor at Pavia and Bologna, author of a commentary on Mundinus. He showed the mythical character of the rete mirabile which Galen had described as existing on the internal carotid arteries (as in the herbivora), and was the first to deny that orifices existed in the interventricular septum. He stated that he had dissected more than a hundred cadavers, but does not say that these were all human. Marcus Antonius (Marc Antonio della Torre, 14S1- 1512), professor at Padua and Pavia, the pupil of Lionardo da Vinci who is said to have designed plates for his work. Lionardo was himself an anatomist fully equal to any of the pre-Vesalian epoch. He made many dissections and carefully reproduced them in drawings that show a great deal of anatomical knowledge. William Hunter says: " I expected to find in the drawings of Lionardo da Vinci at most only the anatomical indications indispensable for a painter in practising his art; but to my great astonish- ment I discovered that Lionardo had studied anatomy as a whole and that very profoundly. When I consider the care with which he studied every part of the human body, I am persuaded that he ought to be considered the best and greatest anatomist of his epoch." He seems to have come nearer to the circulation of the blood than any of his contempora- ries. "The heart," he says "is a muscle of great strength, much stronger than the other muscles. The blood that returns when the heart opens again 328 REFERENCE HANDBOOK OF TIIF. MEDICAL SCIENCES Anatomy, History of j, not the same as that which closes tin 1 valves." It should I"' remembered thai Raphael, Michael Angelo, Bandinelli, Pollajuolo, Verocchio, and Donatello all studied anatiitiiy and left anatomical drawings, Concerning Michael Angelo, the slanderous story was circulated that he had practised vivisection of a criminal in order to gel the expression that ho desired to portray in a picture of the crucifixion. Vidus Vidius (Guido Guidi, 1545-1569), physician to Francis [., and professor at Talis and Pisa, whose name is retained in the Vidian canal and t ho Vidian nerve; Guintherus Andernacensis (Gtinther von lernach, 1487-1574), professor at I.ouvain and Paris; and Jacobus Sylvius (Jacques Dubois, 1478- 1555), professor at Paris, are all chiefly famous as being the instructors of Vesalius. Gunther had both \ esaiius and Servetus as prosectors in his laboratory at the same time. His description of the valves of the heart is good, and he appears to have been the first to discover that both air and blood undergo changes in passing through the lungs. Sylvius fly improved nomenclature, assigning designa- tion- to muscles and vessels, distinguishing voluntary from involuntary muscles, and demonstrating more by personal dissection than was done in other schools. In his little "Introduction to Anatomy" he says: ■■ 1 would have you look carefully and recognize by eye when you are attending dissections or when you see anyone else who may be better supplied with instruments than yourself. For my judgment is that it is much better that you should learn the manner of cutting by eye and touch than by reading and listening. For reading alone never taught any- how to sail a ship, to lead an army, nor to com- pound a medicine, which is done rather by the use of one's own sight and the training of one's own hands." fie discovered valves in some of the veins, but appears to have had no idea of their function. The time was now ripe for a new advance. The invention of printing and consequent general dif- fusion of ancient literature, the discovery of new countries and continents, the progress of invention and the flourishing condition of pictorial and plastic art, created an intellectual activity that would no longer brook the restraints of schools and the un- supported dicta of the ancients. The power of tradition, which had weighed like an incubus upon anatomical teaching for over thirteen hundred year-, was now to be rudely shaken. There arose a group of anatomists who were to pursue their work again in the proper spirit of free inquiry and to institute for the first time in the history of the science of careful examination of the human body made with thorough- ness and skill. The chief of these was Andrew Wesel, more commonly known by his Latin ap- pellative of Andreas Vesalius, who was born at Brussels, December 31, 1514. He was the son, grand- son, and great-grandson of distinguished physicians, a fact of which he was justly proud. He showed a taste for anatomical investigations at an early age, and after an excellent training in Latin, Greek, and perhaps in Arabic, at the university of Louvain, he went to Paris to work in the laboratory conducted by Vidius and afterward by Sylvius at the school founded in 1.330 by Francis I. His description of the way in which anatomy was pursued there shows the state of teaching at that time. The demonstrations were mostly upon animals, and upon those rare occasions when the human body was examined it was hurried over in three lessons, the teacher merely opening the great cavities and so hastening over the demonstration that "more anatomy might be learned in the shop of a butcher than in such a dissecting room." Except the eight muscles of the abdomen which were badly mangled and improperly prepared, not a muscle was demonstrated, nor were any bones shown, much less were nerves, veins, and arteries properly dissected and displayed. At odd times Ve aim haunt'-,! tin- city Cemeti ii' to procure chance hour- turned up by t he spade of the Sexton. He early noted errors in the description "I Galen and Mundinus. Returning to Louvain he con- ducted anatomical demonstrations there, and pos- Sessed himself, it is said, of an entire human skeleton by remaining all night beyond the city gates and robbing the gibbet of a bnd\ partially destroyed by birds. Jle afterward went to Italy, and received, in 1537, at twenty-three years of age, the appointment of professor of anatomy at Padua, already famous for its anatomical instruction. II. n- he at once achieved a striking success. His demonstrations were crowded; the clergy, the laity, even women thronging to hear him. He remained in Italy seven years, delivering courses in I'isa and Bologna as well as at Padua, a proceeding rendered possible by the short duration of each course, viz., seven weeks. While not employed in teaching he gave his time to the composition of his great work, " De Huniani Corporis Fabrica, Libri VII.," the first attempt at a complete exposition of the structure of the human body. In this we find the result of his own personal re- searches, a careful and generally accurate description of the anatomical features of man made for the first time from actual inspection. As Vesalius himself says, it is an attempt to demonstrate the structure of man upon himself. Galen's many errors, caused by his almost exclusive study of inferior animals, were unsparingly noted. Excellent plates made from drawings of preparations illustrated the work. These were so good that they were often ascribed to Titian, but they were probably the work of Stephen von Calcar, one of Titian's pupils, with perhaps some aid and advice from the master and an occasional drawing from Vesalius himself, who was skilful with the pencil. From this epoch-making work modern anatomy may be said to have its birth. It is, however, by no means free from errors, both those due to hasty preparation, and those arising from the preconcep- tions then current. Vesalius still supposed that mucus passed through the holes in the cribriform plate, that the tubular nerves distributed animal spirits, etc. Many of his errors were pointed out by his contemporaries This new departure should be considered as belong- ing to the movement of the age. As has been already noted, the world was becoming impatient of tradi- tionary authority and seeking for facts by personal observation and research. Vesalius' great work appeared in 1543, in the same year that Copernicus published his treatise "On the Motions of the Heav- enly Bodies"; it was in 1521 that Luther made his memorable appeal before the Diet of Worms, and in 1534 that he completed his translation of the Bible. The adherents of ancient tradition did not yield without a struggle. Vesalius was denounced by many, his former teacher Sylvius calling him an impious madman whose breath poisoned Europe. The errors of Galen which Vesalius had pointed out were explained in the most grotesque manner, either by supposing a corruption of Galen's text, or by the hypothesis that the human body had changed since Galen's time. The seven pieces of the sternum which Galen had described (from apes) were supposed to indicate how much larger and more developed the thorax was in Galen's time; the curvature of the thigh bones, not seen in modern man, was said to be their natural free condition before they were straightened by the wearing of tight breeches. More important were criticisms directed toward Vesalius' own demon- strations by Eustachius, who pointed out a number of errors, and thoroughly disapproved of the conduct of Sylvius. Vesalius seems to have taken this opposition very much to heart. He had previously resigned his chair, and now he went to Madrid, where, in the gloomy 329 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES court of Philip II., he found a most uncongenial atmosphere. He was surrounded by enemies who attempted to stop his work by the power of the In- quisition. Philip asked from the University of Salamanca an opinion as to the permissibility of dissection, and the reply of the learned doctors was that since it is useful to man it may be allowed (1556). Restless and ill at ease, Vesalius wished to return to his chair in Italy, now vacant by the death of Fal- lopius. He was destined never to do this. Making a voyage to Palestine in the fulfilment of some vow,* recalled while there by the Senate of Venice to re- sume his chair, he was shipwrecked on the island of Zante, and suffered so much from exposure that he died there, October 15, 1564. He was one of the great pioneers and pathmakers of science, worthy to rank with Copernicus and Columbus. Anatomy has never lost the impulsion due to his arduous efforts. He found it a mass of crude speculations based on ancient authority, he left it a recognized science hav- ing for its basis actual observation of structure. ■ Vesalius was by no means alone. Two other great figures stand out at this epoch, Eustachius (Barto- lommeo Eustacchi, 1520-1574), professor of an- atomy at Rome, and Fallopius (Gabriele Fallopio, 1523-1562), professor at Ferrara, Pisa, and Padua. It is to Eustachius that we owe the first idea of in- vestigating the tissues, also the conception that to understand adult structures we should examine the fetal ones. To correct the current errors in Vesalius and others, he prepared a great illustrated work on the controversies of anatomists, but it was never published, and the plates that he had made for it at great expense were long supposed to be lost, but were finally discovered in the Vatican library and presented by Pope Clement XI. to Lancisi, who published them in 1714. They were the first copper plates used for anatomical illustrations, and show that their author had anticipated many of the discoveries of his successors. The Gasserian ganglion and the pan- creatic duct are clearly shown, and the ciliary muscle not only figured but given its modern designation. The name of Eustachius is preserved in the Eustachian tube, said to have been first discovered by Alcmreon, and the Eustachian valve of the fetal heart mentioned previously by Jacobus Sylvius. He first described the membranous cochlea and the tensor tympani muscle, the origin of the optic nerve, the suprarenal capsules, and the ventricles of the larynx. Fallopius was especially renowned for his exact description of the organs of hearing. He discovered the facial canal and its hiatus, the communication of the mastoid cells with the middle ear, the fenestra ovalis, the chorda tympani, the aqueductus vestibuli, and the lamina spiralis. He gave the membrana tympani its present name and named the oviducts (previously discovered by Herophilus) the tuba' seminales. The inguinal ligament (Poupart's) was first described by him, as also the hymen, the clitoris, the seminal vesicles, and the uriniferous tubules. He also described the ileocecal valve, which was, however, probably known to Achillinus. He discussed the development of bones and teeth, and knew the ganglia of the spinal nerves. In their zeal for knowledge the anatomists of that age are reputed to have not infrequently overstepped the bounds of common humanity. Vesalius, following the example of Herophilus, is said to have vivisected criminals, and the records found in the criminal archives of Florence (1545-1570) show beyond dis- pute that it was by no means uncommon to send living persons to Pisa "to be made an anatomy." While this language seems to indicate that such * The report that he was condemned to death by the Inquisition for opening by accidenl the body of a living man, and that his sentence was by Philip commuted t<> a pilgrimage, appears to be wholly without foundation, unsupported by the records of the Inquisition or of 1 he royal archives. subjects were dissected alive, there is, on the other hand, some evidence to show that they were first executed by smothering or otherwise. Many other almost equally famous men contrib- uted to the anatomical knowledge of the period. Among these are the following: Servetus (Miguel Serveto, 1509-1553), a Spaniard from Villanova, in Arragon, burned at the stake by Calvin, at Geneva, for heretical opinions. He was the first clearly to describe the pulmonary circulation and the change from venous to arterial blood that occurs in the lung. This description occurs in the rare work " Christianismi Restitutio," published by him at Vienne in 1553. In this he clearly states that air mixed with blood passes from the lungs to the heart. "A pulmonibus ad cor non simplex aer sed mixtia sanguine mittitur per arteriam venosam." He had, however, no idea of the greater or general circulation. Columbus (Matteo Realdo Colombo, 1494-1559), a bitter opponent of Vesalius, and who immediately succeeded him at Padua and afterward taught at Pisa and Rome, dissected with great assiduity, completing at least fourteen bodies in a year. He also ransacked old charnel houses for bones and is said to have compared about half a million of skulls. He was an ardent investigator, demonstrated ex- perimentally the lesser circulation, perhaps with knowledge of the prior work of Servetus, and had an accurate idea of the functions of the valves of the heart. Ingrassias (Giovanni Filipo Ingrassia, 1510-15S0), professor at Naples, of high rank as an osteologist, who discovered the stapes and studied the sphenoid and ethmoid bones. Cananus (Giambattista C'anano, 1515-1579), one of the earliest to mention the valves of the veins (1547). Coesalpinus (Andreas Cfesalpini, 1519-1603), the first to use the term circulatio in speaking of the move- ment of the blood. He seems to have anticipated Harvey in holding that the blood returns from the general tissues to the heart by the veins alone. He lacked, however, the precise demonstration which characterizes Harvey's work. Arantius (Giulio Cesare Aranzio, 1530-1589), professor at Bologna, who discovered the ductus arteriosus, the corpora Arantii, named the hippo- campus major, carefully described the gravid uterus, which he considered a muscular organ, and first spoke of a separation of the maternal and fetal blood. Coiterus(VolcherKoyter, 1534-1600), of Groningen, who investigated the osteology of the fetus and the de- velopment of the bones. Varolius (Constanzo Varolio, 1543-1575), pro- fessor at Rome, who made special researches into the brain and nervous system, describing the base of the brain and the apparent origin of the cranial nerves. His name is preserved in the pons Varolii. Bauhinus (Caspar Bauhin, 1560-1624), professaj at Basle, who made improvements in terminology, (The discovery of the ileocecal valve, ascribed to him, is apparently due to Achillinus.) Spigelius (Adrian van den Spieghel, 1578-1625), of Brussels, who made a special study of the liver, one of whose lobes still bears his name. Fabricius ab Aquapendente (Girolamo Fabrizio, 1537-1613, so called to distinguish him from Fabriciua Hildanus, a celebrated surgeon of the period), who was the successor of Fallopius at Padua, and worthily maintained the reputation of that celebrated school. He erected at his own expense an anatomical amphi- theater which still remains. It is a small dark pit with seats risintr almost perpendicularly about it, excluding the light so that all dissections must have been by candle light! It was here that Harvey learned anatomy ami obtained from Fabricius the germs of the knowledge which was to result in the discovery of the circulation of the blood. Fabricius 330 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anatomy, History »t was the first to demonstrate in a complete manner the valves of the veins. , The first mention of these i~ by Stephanus (Charles Etienne) of Paris in 1545, who , to them as "apophyses membranarum," in- tended to prevent the regurgitation of the blood. Sylvius i 1555) noted them in several veins, Eustachius in the coronary vein (1563). Vesalius seems not to have realized their importance, but figures them in the hepatic veins. Fabricius, however, wrote a cum; treatise upon them ("De Venarum Ostiolis," 1603 and .stated that they prevent the overdistention of Is when blood passes from the larger to the small- er veins. He also .studied the development of the human fetus and of the embryo chick, tho muscular of the bladder, tho esophagus, stomach, and intes- tines, particularly the appendix vermiformis. He was leeded at Padua by C'asserius (Giulio Casserio, 1561-1616), who paid especial attention to the organs of voice and hearing and discovered the stapedius muscle. The musculo-cutaneous nerve of the arm is sometimes called the nervus perforans Casserii. The zeal for investigation instituted by Vesalius and carried on by his contemporaries and immediate was undoubtedly a great advance over the ignorant apathy that preceded it, but it was not so ij a new movement as a revival of an old one. The anatomy of that time was, after all, the anatomy of the Greeks, carried to a greater degree of detail, it is true, but marred by the same teleological errors. The spiritualistic theories of Hippocrates, Aristotle, and Qalen still prevailed and blinded the eyes of anato- mists to the true significance of structure. The doctrine of the tissues, hinted at by Aristotle, and dimly groped after by Eustachius and Fallopius, had borne as yet no fruit. The development of the embryo had been but little studied and its details were im- perfectly known. In osteology and arthrology the advances were greatest, the general features of the ■s, joints, and ligaments being well described; but their nomenclature was as yet undeveloped, they being mated in each region by numbers. In the vascular system the veins were considered the most important vessels, it being supposed that the blood in them had an oscillatory movement which the valves modified without absolutely controlling its direction. The heart had been fairly well described, but as no one had shown experimentally the impossibility of regur- gitation of blood into it from the aorta and the pulmon- ary artery, it was still supposed to be a sort of mixing reservoir for the blood and animal spirits. The permeability of the interventricular septum was still in dispute, it being held necessary for the mixing of the blood. The powerful muscular character of the heart was still unrecognized, and though the lesser or pulmonary circulation had been mentioned by Bervetus and Columbus, it was not generally ac- cepted. The lymphatics, although seen and vaguely mentioned by several ancient authors, were not understood. The macroscopic anatomy of the brain was not yet well known; the ventricles were supposed to be the reservoirs of the vital spirits, and the nerves to be tubular in character. The distribution of the cranial nerves was not clearly made out. In splanchnology vague ideas prevailed. The liver and spleen were thought to be potent organs for the elaboration of blood, which was made in them as fast as it was distributed by the heart through the veins and arteries to be poured out into the substance of the organs. The pancreas, although discovered by Herophilus, was overlooked, as it is evident that \ esalius mistook for that organ the collective mesen- teric glands. The ovaries were believed to produce a female semen. Anatomical instruction was still carried on mainly by demonstrations by the professor. The prosectors usually made dissections in sight of the pupils, the professor sitting opposite and with, a little wand pointing oui the part described. The muscles dissected in one day, the contents of the head, chi t, and abdomen in a second, the bones and ligaments in a third. It was not usually practicable to extend this lime on account of the rapid decay oi tie- body. As, however, the whole day was occupied by each demon- tration, the work was nut as superficial as might at first appear. Another great advance was now made in a domain which, although physiological in its scope, yet reacted powerfully upon anatomy by affecting conceptions of bodily structure. This was the careful inductive demonstration (commonly called discovery) of the circulation of the blood made by the renowned William Harvey who was born April 1, l~>7s. He studied at Cambridge and Padua, graduating from both universities in lfi()2. In Italy he became ac- quainted with the views of Fabricius whose pupil he was, as to the wide distribution of the valves of the veins, and those of Columbus regarding the pulmonary circulation. It was not, however, until lie had made many vivisections and studied the movements of the heart in many living animals, under varying conditions, that he attained to a correct idea of the double circuit made by the blood. Harvey began to teach the new doctrine in his lectures at the Royal College of Physicians as early as 1615, but did not publish them until 1028, when appeared, at Frankfort, his "Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus" (An anatomical treatise on the movements of the heart and the blood in animals). In this he frankly breaks with traditional teaching: " I profess to learn and teach anatomy not from books, but from dissections; not from the suppositions of philosophers, but from the fabric of nature."* Showing that the anatomical arrangement of the valves of the veins and of the heart necessarily implies a movement of the blood from the veins toward the heart and from the heart into the arteries, he demonstrated such movement by a compression of veins and arteries and by various other experiments in living animals, making an ear- nest plea for comparative anatomy: "Had anatomi-ts only been as conversant with the dissection of the lower animals as they are with that of the human body, the matters that have hitherto kept them in a perplexity of doubt would, in my opinion, have met them freed from every kind of difficulty." For the first time we see doubt cast upon the doctrine of "spirits." Says Harvey: "We are too much in the habit of worship- ping names to the neglect of things. The word blood has nothing of grandiloquence, about it, for it signifies a substance which we have before our eyes and can touch; but before such titles as spirit and innate heat we stand agape." The new doctrine was at first universally rejected, especially in Italy where most of the preliminary discoveries had been made that led to Harvey's con- elusions. As in the case of Vesalius, the innovator was greeted with abuse and detraction instead of demonstration and legitimate argument. Harvey received this, however, with a singularly calm and judicial spirit. He says: "To return evil speaking with evil speaking I hold to be unworthy in a philoso- pher and searcher after truth. I believe that I shall do better and more advisedly' if I meet so many indica- tions of ill-breeding with the light of faithful and con- clusive observation." The only opponent he deigned to answer was Jean Riolan (Riolanus, Jr., 1.577-1657), professor at Paris, so renowned for his acerbity in con- troversy that it was said of him that he would rather give up a friend than yield an opinion. Harvey's * In the possession of the Royal College of Physicians of London are preparations of tin- blood-vessels, mounted on boards and show- ing the aortic valves, that are said to have been prepared by Har- viv when a student in Italy and used for demonstration to his classes. Hyrtl believes them to be the oldest anatomical prepara- tions extant. 331 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES reply was judicial and complete, but failed to con- vince Riolan, who obtained a decree from the Faculty at Paris forbidding the teaching of the new doctrine, and opposed it up to the time of his death. Harvey lived to see his views almost universally accepted, dying in 1657, a few years before Malpighi discovered the capillaries and thus placed the anatomical basis of the circulation beyond cavil (1661). Harvey's work called more attention to the heart, and many points in its gross anatomy were now estab- lished. Among those who worked to this end may be mentioned Richard Lower of London (1631-1691, tuberculum Loweri), Raymond Vieussens(1641-1715 or 16, fossa ovalis), professor at Montpellier, Nils Stensen (Nicholas Stenonis, 1638-16S6), professor at Copenhagen, who worked at the musculature and looped fibers, and Adam Christian Thebesius (1686- 1732), who discovered the foramina Thebesii. As a consequence of the doctrine of the circulation, the distribution of blood-vessels was more accurately studied. A passage in Sylvius is sometimes cited to show that he suggested injections, but it is clear that he could not have made any effective use of them. The first to do this was Stephen Blancaard, of Middle- burg, Holland (1650-1702), who, in 1675, succeeded in injecting the blood-vessels. Others obtained great success with this method, especially Frederick Ruysch (1638—1731), professor at Amsterdam, whose prepara- tions were justly famous. It is to him we owe the dem- onstration of the vascular distribution in the choroid of the eye (tunica Ruyschiana =choriocapillaris). Using fine injections he found vessels in every part of the body in such numbers that he inclined to the belief that the body was mainly composed of them, "totum corpus ex vasculis." Closely associated with the anatomy of the blood- vascular system is that of the lymphatics. These structures were probably seen in goats by Aristotle and Herophilus, but as their course and termination were not determined, the remarks of those authors concerning them were overlooked or misunderstood. Eustachius saw and described the thoracic duct in the horse, supposing it to be a vein for the nourishment of the thorax. The chyliferous lymphatics were first ob- served in 1622 by Gaspare Aselli (1581-1626), professor at Pa via, in the mesentery of a dog lately fed. Misled by the prevalent conceptions as to blood formation, he thought they could be traced to the liver. His dis- covery was not published until 1627, and the next year such vessels were demonstrated in the mesentery of a criminal two hours after death by Fabrice de Peiresc, a senator of Aix, to whom Gassendi had com- municated Asellius' discovery. In 1647, Jean Pecquet (1622-1674), a student at Montpellier, accidentally discovered the thoracic duct in a dog and traced it through the diaphragm to the receptaculum chyli (reservoir of Pecquet). It was still considered a vein, though further research showed its connection with the mesenteric glands. The distinction between the lymphatics and the mesenteric veins was first made by Nathanael Highmore (1613-16S4), of Shaftesbury. Jan Van Home (1621-1670), professor at Leyden was the first to observe the thoracic duct in man, though Olaus Rudbeck (1630-1702), professor at Upsala, noted it about the same time. The latter also dis- covered the general lymphatics, distinguishing them as vasa serosa in 1651, their present name being given by Thomas Bartholin (1616-1680), professorat Copen- hagen, who greatly extended the knowledge of them. Finally Anton Nuck (1650-1692), professorat Leyden, invented the method of injecting these vessels with mercury and traced them to nearly all parts of the body. It was at about this period that anatomical science obtained great assistance by the invention of the microscope. As an instrument of research the simple microscope was not used until the seventeenth century, although the magnifying power of lenses seems to have been known in remote antiquity. The greater power of the compound microscope invented about 1608 by Hans and Zacharias Janssen, of Middelburg, Holland, still further stimulated inves- tigation and led to the discoveries of Malpighi, Leeuwenhoek, Redi, and others. The imperfection of the instrument so greatly affected its utility that many anatomists distrusted the results obtained from its use. After many attempts and partial successes by others, Chevalier of Paris (1824) and Amiei of Modena (1827) finally succeeded in correcting chromatic and spherical aberration, thus producing an instrument by which minute structure can be accurately investigated. The immediate result of microscopical investigation was, on the one hand, greatly to extend the knowledge of structure, and, on the other, to introduce novel ideas regarding generation and the diffusion of animal life. Marcello Malpighi (1628-1694), professor at Bologna, Pisa, and Messina, a man of great scientific force, laid the foundations of modern botany, of histological anatomy, and of embryology. His discovery of the capillaries in the lung of the frog has already been mentioned. Molyneux (1683) and Leeuwenhoek (1688) almost immediately extended this by finding them in the extremities of lizards and tadpoles. Malpighi discovered the red corpuscles of the blood in 1665 and thought them to be fatty globules. He was, however, anticipated in this by Johannes Swammerdam (1637-1680) who not only saw them but correctly described them in 1658. Malpighi published the first accurate account of the consecutive development of the chick, carrying his investigations as far as the imperfect instruments and methods of his time would permit. He greatly advanced the knowledge of glands, showing the structure of acini and ducts, demonstrated the glomer- uli of the kidney and the splenic corpuscles which still bear his name, and by inflating the air vesicles showed the glandular structure of the lungs and the impossibility of air passing into the vessels by mechanical means. Misled by his imperfect instru- ments and crude methods of preparation he endeav- ored to show that the brain also has a glandular character. Having cooked the organ he thought that the gray matter appeared on examination to be composed of minute spherules connected with the fibrous central portion. He assumed that these spherules secreted the nervous fluid which was dis- tributed by the nerves. This accorded with the prevalent ideas and greatly retarded a true apprecia- tion of the structure of the brain. Many other anatomists added to our knowledge of glands: Francis Glisson (1597-1677), professor at Cambridge, gave a description of the liver that is the basis of our knowledge at the present day; Johann Georg Wirsung, professor at Padua in 1642, discovered in man the pancreatic duct, alleged to have been previously found in the fowl by his pupil Moritz Hofmann (1621-1698), afterward professor at Altorf; a discovery that retarded rather than advanced anatomical science, for the pancreas was supposed to be a lymphatic gland and the duct a lymphatic leading from the intestine to the liver, and thus were confirmed erroneous views of lymphatic distribution; Thomas Wharton of London (1610-1673) wrote of the nature and classification of glands, and discovered the duct of the submaxillary gland that bears his name. At Paris a remarkable advance was made by the establishment by Jean Riolan, Jr., of the Jardin du Roi, afterward the Jardin des Plantes, which was, in effect, a biological laboratory where various prob- lems of human and comparative anatomy could be studied. Jean Guichard Duverney (1648-1730) was an able demonstrator there, so popular that noblemen flocked to hear him. He discovered the vulvovaginal glands (in the cow), to which Caspar Bartholin's 332 REFERENCE HANDBOOK OF THE MEDICAL SCIENt ES Anatomy, History of name was afterward attached. H>' also confirmed the existence of the bulbourethral glands, first discovered by Mery (1645-1722) and named after nglish anatomist Cowper. \1, ixis I.ittrc i Hi.")S-17'_'(i) described the urethral elands that bear bis name, and Martin Naboth (1675-1721) the glands of the neck of the uterus and the closed follicles of the same region. Lorenzo Bellini (1643-1704), professor at Pisa, examined , - fully the structure of the kidney (uriniferous tubules). Thomas Bartholin (1616-1680), professor at Copenhagen, one of the most distinguished anatom- ists ef the seventeenth century, discovered the duct of the sublingual gland which joins Wharton's duct, while the ducts of that gland that open separately into the mouth were found by August Quiriu Bach- i (Rivinus, 1652-1723), professor at Leipsic. The duet of the parotid gland, seen and described as I iment by C'asserius, was first recognized as a duct by Walter Needham, of London, in 1655. Nils sen i Nicholas Stenonis, 1638-1(386), professor ipenhagen, mentioned it in his inaugural thesis in , and its discovery is often assigned to him. Stensen was one of the most able thinkers of his time. He held that in order to understand the function of organs we must first determine their structure, and that no accurate knowledge of the brain can be had until we understand its conducting tracts. He declared, contrary to the prevailing opinion, that petrifactions are not mere erratic freaks of nature, but the remains of plants and animals that formerly lived. The glands of the intestinal tract were investigated by Johann Conrad Brunner (1653-1727) and Johann Conrad Peyer (1653-1712); those of the eye-lids by Heinrich Meibom (1638-1700), professor at Helmstadt; while Conrad Victor Schneider (1614- 1680), professor at Wittenberg, demonstrated the true nature of the lining membrane of the nasal fosse, and thus overthrew the ancient doctrine of the tion of mucus (pituita) by the brain and of the cerebral origin of catarrhal disorders. Antonio Pacchioni(1665-1726), professor at Rome, discovered the bodies that bear his name, situated near the superior longitudinal sinus; and the synovial fringes and so-called synovial glands were described by Clopton Havers (1692). The Pythagorean and Galenical doctrine that the embryo is formed from two kinds of semen, generated respectively by the male and female, was generally held. Harvey, following in the footsteps of his master Fabricius, investigated the course of develop- ment not only in fowls but in mammals, and published (1651) a treatise on development in which he formu- lated the famous proposition that the egg is the primary stage of development for all animals. The original phrase is, "Ovum esse primordium commune omnibus animalibus," afterward currently abbreviated as, "Omne vivum ex ovo." According to this view the ovum is the essential element in the generative process. This belief was shaken by the discovery, in 1(>77, by Johann Ham, a pupil of Leeuwenhoek, at Leyden, of the spermatozoa, which were at once accepted by many as the true generative elements, and were even considered to be minute but completely formed creatures, possessing in miniature all the organs of the adult. There thus arose two schools, the Animalculists and the Ovists, that respectively maintained the efficacy of the male and female products. Nathanael Highmore (1613-1684), a phy- sician of Shaftesbury, England, investigated the testicle, the seminal ducts, and the epididymis. His name is preserved in the corpus Highmorianum (mediastinum testis) and the antrum of Highmore (maxillary sinus). Wharton described the round ligament of the uterus as the excretory duct for the female semen, but the question of this hypothetical product was finally settled by Caspar Bartholin, who correctly described the functions of the vulvo- vaginal glands. The mammalian ovum eluded research for a long time. The ovisacs (Graafian follicles) were described by Etegnier de Graaf (1641 1673), who says that they were known and mentioned by Vesalius and others. He supposed them at first to be ova, though he ei m later to have had a correct idea of their nature. When Naboth discovered the closed follicles of the luck of the uterus, he too supposed that he had found the ova (nvula Nabothi). It is said that Van Borne I 1621-1670), professor at Leyden, saw the ovum in Kills, but it was not definitely and unquestionably recognized until von Baer demonstrated it in L827. Nicolas Andry do Boisregard (1658-1742) was the first to note the entrance of a spermatozoon into an ovum, and believed that it did this in order to feed. Antonio Vallisneri (1661-1730), professor at Padua, held, on the contrary, that the ovum was necessary for generation, and supposed the spermatozoon to be unessential. Needham first showed that the fetus was nourished by maternal blood. In the nervous system considerable advances were made during this period. Although Harvey stated that he was unable to discover the animal spirits, yet he does not seem to have been able wholly to free himself from the influence of the prevailing doctrine. Ren£ Descartes (Cartesius, 1596-16.50,) the eminent mathematician, held that although the soul was im- manent throughout the whole body, it must be specially centralized in the pineal gland, that being the only unpaired organ of the brain and situated so as effectually to control the animal spirits contained in the ventricles. He held that the brain is the seat of sensation, motion, and thought, sensation being due to impulses transmitted to that organ by nerves, motion to the contraction of muscles induced by impulses also transmitted by the nerves. He seems to have been aware of reflex action, noting that sen- sation may cause motion independently of the will. He thus anticipated discoveries made nearly two hundred years later, and was the first to attempt to explain the phenomena of life by purely physical causes. He was a warm adherent of Harvey's doctrine of the circulation, though he would not admit that the blood was impelled by the action of the heart. Johann Jacob Wepffer (1620-1695) was the first distinctly to deny that spirits were generated in the cavities of the brain. Pacchioni considered the dura mater as an organ for effecting the circulation of the spirits, and provided it with three muscles and four tendons. Francois de le Boe (Franciscus Sylvius, 1614- 1672), professor at Leyden, carefully studied the brain and gave true ideas of its interior spaces. His name is preserved in the aqueduct, fissure, fossa, and artery of Sylvius. The fifth ventricle which he discovered is sometimes called the Sylvian ventricle. Raymond Vieussens (1641-1715), of Montpellier, also investigated the brain. He was the first to describe the anterior pyramids of the medulla oblon- gata, the olive, and the centrum ovale. His name remains in the valve of Vieussens or anterior medullary velum. Duverney described the decussation of the pyramids and the connection of the jugular sinuses with the jugular vein; while Humphrey Ridley (1653—1708) described the restiform body and the circular sinus. Malpighi recognized the functional importance of the gray matter of the brain, and Burrhus (1616-1695) showed that one-fourth of the cerebral substance was a spermaceti-like fat. Much advance was made by the investigations of Thomas Willis (1622-1675), professor at Oxford, who showed that the brain gradually increases in complexity as we ascend the animal series, and considered that only by comparative studies could its anatomy be prop- erly understood. He renamed and rearranged the cranial nerves, separating the nervus intercostalis or sympathetic from the vagus. In his enumeration he 333 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES made ten pairs, including the first cervical nerve, and classing as single pairs the auditory and facial, and the glossopharyngeal, vagus, and spinal accessory. He described the optic thalamus and the corpus striatum. Osteology continued to be assiduously cultivated. It is from Ole Worm (158S-1054), professor at Copen- hagen, that the Wormian or sutural bones are named; and Clopton Havers (1692), an English physician, demonstrated the structure of bone (Haversian canals and systems). The structure and action of muscles were specially investigated by Stensen, by Borelli (1608-1679), the celebrated mathematician, and by Hooke. (1635-1703), who was the first to recognize the primitive fibrillar. Knowledge of the viscera was essentially advanced by John Mayow (1643-1679), of Oxford, who was the first to recognize the true function of the lungs; by Theodor Kerckring of Amsterdam (1640-1693), who described the valvuke conniventes (plicae circulares BNA) of the intestine; by Jacques Benigne 1 Winslow (1669-1760) of Paris (foramen of Winslow, posterior ligament of knee joint), and by James Douglas (1675- 1742) of London (Douglas' pouch of peritoneum, semilunar fold, etc.). The eye was specially examined by several investi- gators, who considered it because of its interest as an optical instrument. Among these we may mention Johann Kepler (1571-1630) the astronomer, who demonstrated the optical properties of the crystalline lens and showed that it is not the seat of vision, as was held by Hippocrates; Christoph Scheiner (1575- 1650), who demonstrated the image on the retina and studied the movements of the pupil and the mechanism of accommodation; Descartes, who compared the eye to a camera obscura and suggested that accom- modation for near vision was effected by changing the figure of the lens; and Edme. Mariotte (1620-16S4), who discovered the "blind spot" of the retina. Another great result of the introduction of the mi- croscope was a vast increase in the knowledge of living things. The source of life and the "vital principle" had been favorite subjects for speculation among the philosophers and poets of antiquity, and the generation of living from non-living matter was held to be demonstrated by many ordinary phe- nomena, such as the appearance of maggots in putrefy- ing meat and of other insect larva? in stagnant water. Aristotle even held that tadpoles and snakes were generated from the mud of the Nile. As the laws of development were more carefully studied this "generatio oequivoca" was controverted, especially, in the case of the chick, by Harvey and Fabricius. Francesco Redi (1626-1694), professor at Pisa, by a scries of well-conducted experiments, showed that meat did not produce maggots when protected from flies by means of gauze. The doctrine, discarded for the higher forms of life, was, however, revived by the discoveries of the microscope. Antony van Leeuwenhoek of Delft (1632-1723) discovered that stagnant water and infusions containing animal or vegetable matter swarmed in a few days with minute forms of life, the "infusoria." Nicolaas Hartsoeker (1656-1725) extended these researches and held that the air was filled with animalculce that settled upon plants and from them passed into infusions. This view, afterward conclusively demonstrated by Spal- lanzani, became known as "panspermatism" and is the forerunner of the modern "germ theory." The eighteenth century was distinguished rather for its work in elaborating and defining what had previously been discovered than by any great ad- vances in anatomical science. A few remarkable men appeared who advanced generalizations that were afterward to bear fruit, but they were in advance of their time and had but little influence upon their contemporaries. The microscope was still very defective and felt to be a wholly untrustworthy instrument when used with the higher powers. Speculation was rife, and in the absence of direct observation philosophers held the field. Of these should be mentioned Leibnitz (1646-1716), who shares with Newton the renown of inventing calculus. He supposed the universe to be composed of monads, minute, invisible, intelligent constituents of all bodies and beings, that in the human body are gov- erned by a central monad, the soul; as the universe is governed by a central monad, God. He was a firm believer in the uniformity of action of natural causes and the author of the celebrated aphorism, " Natura mm facit saltum." Like Paracelsus, Georg Ernst Stahl (1660-1734) scorned anatomy and physiology, holding the soul, which eludes investigation, to be the supreme principle. This doctrine was termed "animism." Friedrich Hoffmann (1600-1742), pro- fessor at Halle, taught that the medulla oblongata is the chief reservoir of collier, an extremely volatile principle circulating through the vessels and nerves. David Hartley (1705-1757) considered the white medullary substance of the brain as an organ for the secretion of thought, and explained mental processes as caused by minute vibrations (vibratiuncles) of particles in the nerves. Cabanis (1757-1808) had a similar idea, which he expressed rather grossly, com- paring the brain to the stomach, sense impressions to food, thought to excrement, etc. Theophile de Bordeu (1722-1776) considered the stomach, heart, and brain as the "tripod of life," regulating the other organs. Finally, there should be mentioned among these speculative philosophers Lorenzo Oken (1779- 1851), who held that the entire organic world origi- nated from sea slime formed of microscopically minute vesicles. This is apparently an adumbration of Bathybius and the cellular theory, but appears to be only a chance hit not derived from observation. Oken also independently worked out a theory of the veretebral character of the skull, but many of his speculations were wild and absurd. It is in this century that we first see the influence of speculative ideas concerning the relation of the structure of man to that of other organisms — ideas which have had a powerful effect upon modern ana- tomical science. The collection of materials in the field of biology had become so vast that some system of classification became necessary. Steps toward this were first taken in the realm of plants by John Ray (1628-1705), who revived the Aristotelian idea of genera and species and established, as criteria for species, immutability of form and non-fertility with other species. Tournefort (1656-1708) gave a clear definition of a species as individuals having some dis- tinct characteristic, and of a genus as a collection of species resembling each other in structure. It was, however, Karl von Linne 1 (Linnaeus, 1707-177S), of Rashult in Smaland, Sweden, professor at Upsala, who, by inventing the binomial nomenclature and applying it widely to all known species of animals and plants, finally established firmly the idea of the immutability of species. He even extended his system of classification to diseases, of which he described three hundred and twenty-five genera. His earlier view was that all the species of plants and animals were immutably created at the be- ginning of the world, but in his later works he ap- pears to admit a certain amount of variation. In the classification of Linne man was placed at the head of the order Primates, comprising also apes, lemurs, and bats. The recently discovered orang was classified in the same genus with man as "Homo silvestris," and the great naturalist declares himself unable to discern any character by which the great apes can be made genericallv distinct from man. The race of man himself, Homo sapiens, he subdivided into six groups: H. fcrus (savage); H. americanus; H. europceus; H. asiaticus; H. asser(negroes) ; H. monstrosus (abnormal). The great rival and contemporary of Linne 1 was George Louis Leclerc de Buffon (1 707-1 7S8), director 334 REFERENCE HANDBOOK <»!•' THE MEDICAL SCIENCES \ li:itom> '. Illstnry of if the Jardin du Roi at Paris, and a very prolific .vriter in all domains of natural history. At Brsl Buffon agreed with Linne - a- to the immutability of species, but in his studies of comparative anatomy met with many difficulties, and soon admitted thai uany variations may arise through changes of climate, uod, etc.; that t he least perfected species disappear: finally he even hinted at the possibility that all ies of animals were derived fr a common stock. While he by no means clearly worked out these ideas, contain the germs of the doctrine of adaptation the survival of t he tit test, and it is evident that he realized that genera and species are merely human ons made for convenience in classification. In like manner we may discern in Maupertuis (1698- . president of the Berlin Academy and a cele- d mathematician and astronomer, an approach ome modern theories of heredity and variation. Il<' held that all matter has psychic qualities, that the particles of the embryo retain and transmit impressions derived from their parents, chance combinations pro- ducing differences which accumulate and thus form new species. It was Charles Bonnet (1720-1793) who lirst advanced the view that animals can be arranged in a graded series with man at the head. His conception of the series was that it was necessarily linear. Erasmus Darwin (1731-1S02), the grand- father of the great naturalist, anticipated some of the - that afterward made his grandson famous. He showed that the structure of animals changes be- se of their exertions, that many of these changes are transmitted to posterityl transmission of acquired characters), and that many anatomical features of man indicate that his primitive attitude was quadru- pedal. Reasoning from such data, he maintained that all warm-blooded animals may have arisen from a single living filament which improved and transmitted its improvements to posterity. The poet Goethe (1749-1S32) was also famous for his morphological researches. Besides the remark- able contribution to botany in which he advanced the thesis of the metamorphosis of leaves into parts of the flower and fruit, he also suggested that the skull of vertebrates is composed of modified vertebrae. He recognized the importance and significance of vestigia] structures and predicted that a premaxillary bone would be found in the human fetus. Widely different from these philosophers who sought to explain the complicated structure of man by the at ions of natural forces, were the views of the eminent philosopher and metaphysician Emmanuel Kant (1724-1804), who held that a great gap neces- sarily exists between organic and inorganic matter, and that while in the latter natural causes prevail, the former is the product of preordained intention, be- yond the power of man to comprehend. Closely allied with these theories of the relation of the structure of man to that of other animals are others regarding his individual deve'opment. The imperfections of the microscope and of technical methods prevented an accurate determination of the earlier embryonic stages, and it was imagined that all details of the completed structures are prefigured in the impregnated ovum. This necessarily involved the conclusion that the successive generations of offspring must also be prefigured in the same manner. Burden accordingly declared that the semen of Adam must have contained the archetype of all mankind. The whole of the past and present organic life of the globe was held to have been contained in miniature in the first created beings, the successive individuals merely developing by growth from these preformed and structurally complete miniatures. This is the celebrated theory of preformation or encasement (cm- boitcment) which has profoundly interested biologists for the past one hundred and fifty years. It was to this unfolding that Bonnet applied the term evolution, a meaning widely different from that now in common use. Tin' great weigh) of authority at lirst favored this view, ami the celebrated Albrechl von Haller 1708— 1777), professor al Berne and Gottingen, a most learned and acute observer, whose reputation v. a greal that he practically controlled the scientific thought of the latter half of the eighteenth century, i alculated the number of i a ed in the ovary of Eve, the mother of mankind, placing it at. about 200,000,000,000. In opposition to this is the theory of post -format ion 01 i pigenesis advanced by Hippocrates and Aristotle, according to which the human body develops from a structureless blastema by successive stages not qi sarily resembling the adult individual. This view was revived by Caspar Friedrich Wolff (1733-1794), who published, in 17.V.I, his now celebrated thesis, "Theoria Generationis," which contained an account of accurate observations showing that the organs of the body are not preformed in the fetus, but devel- oped from membranous sheets (the blastodermic membranes of later embryologists) which are them- selves composed of globules or vesicles (cells). These ideas were not accepted by the anatomists of his day. Opposed to them was the great authority of Haller, who declared, "Nulla est epigenesis," and they were quite forgotten until fifty years later when Meckel called attention to them. Wolff's name remains to us in the Wolffian bodies or primordial kidneys. It was from Haller that the doctrine of the vital and animal spirits finally 7 received its coup de grace. By a series of most carefully conducted experiments he showed that there exists in living tissues a property of motility independent of the nervous or vascular systems. This he termed irritability. Haller is often justly termed the father of physiology, which he him- self loved to call living anatomy. His works abound in most excellent anatomical observations. He was an indefatigable worker, dissecting as many r as four hundred bodies in the space of seventeen years. He classified structures according to their properties and thus paved the way for Bichat. Many structures have been at one time or another named after him. He was the first to describe the pes hippocampi. The doctrine of spontaneous generation continued to be discussed. Antonio Maria Valsalva (1666-1723) professor at Bologna, a pupil of Malpighi and a teacher of Morgagni, finding that living forms still appeared in liquids that he had heated and then enclosed in vessels, concluded that they must have originated from the liquids themselves; but this was overthrown by the experiments of Lazzaro Spallanzani (1729-1799), professor at Reggio, Modena, and Pavia, who repeated the experiments with careful precautions and failed to produce life. It was to this observer that we owe the demonstration that the spermatozoa are the con- stituents of semen essential to fertilization. He showed that the fluid obtained by filtering semen has no effect, also that no exhalations from semen can cause impregnation. Thus were overthrown some of the more fanciful hypotheses of generation. Throughout the eighteenth century we find isolated attempts at generalizing the complicated structures of the body under a few categories. Almost equally famous with Haller for his erudition was Hermann Boerhaave (1668-1738), professor at Leyden, a skilful anatomist who discovered the sudoriparous glands of the skin, and held that the elementary structures composing the body are vessels and fibers. In Andreas Bonn (173S-181S), professor at Amster- dam, we discern a decided advance. He endeavored to show that ail structures can finally be reduced to membranes. Of these he made four classes: (1) the tectorial — skin, mucous membrane, etc.; (2) fibrous — fascia and aponeuroses; (3) synovial, and (4) serous. The real founder of the science of general anatomy was, however, Marie Francois Xavier Bichat (1771- 1S02) who, by his philosophical insight and great energy in research, demonstrated the existence of the 335 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tissues of the body in a complete and definite manner. Distrusting the microscope, he made his distinctions by the chemical, physical, or vital properties of each tissue — i.e. by its behavior with various reagents; by its color, density, etc.; or by its alterations in health and dN^ase. Of these tissues or tissue systems he made twenty-one, such as the cellular, the osseous, the fibrous, the arterial, etc. As these tissues are everywhere the same, their diseases must be identical, hence this separation is a proper foundation for pathological anatomy. He considered life to be the composite effect of the separate interaction of the forces resident in these tissues. He died at the early age of thirty-one, from overwork and disease con- tracted in the putrid dissecting rooms of his day, having effected the greatest advance in anatomical knowledge made since the time of Vesalius. The anatomy of diseased organs was, prior to Bichat, specially investigated by the illustrious Giovanni Battista Morgagni (1682-1771), who may be said to be the founder of pathological anatomy. He was likewise an ardent investigator in the normal field, as will appear from the large number of struc- tures that bear his name; as the caruncula Morgagni (middle lobe of prostate), frenum Morgagni (near ileocecal valve), fossa Morgagni (navicular fossa of urethra), hydatids of Morgagni (on fimbria of Fallopian tube), columns of Morgagni (in the rectum), etc., etc. Closely allied to pathological anatomy is surgical anatomy, which made many important advances. John Hunter ( 172S— lTO^), an indefatigable investi- gator, is said to have dissected some thousands of bodies. It is to him that we owe a demonstration of the ease with which collateral circulation is estab- lished after ligation of vessels, and the reparative significance of inflammation. He also appears to have been aware of the law of recapitulation in em- bryology, by which the fetus of an animal successively passes through forms resembling creatures below it in the animal scale. During thirty years he worked at collecting a museum illustrative of comparative and human anatomy and pathology, which finally comprised some fourteen thousand specimens. It is still considered one of the best extant. It is from him that is named the canal traversed by the femoral artery under the adductor magnus. Other workers in surgical anatomy were Antonio Scarpa (1752-1832), professor at Modena (Scarpa's triangle, fascia, nerve, ganglion, etc.); Franz Caspar Hesselbach (1759-1816), professor at Wiirzburg (Hesselbach's triangle); Antonio de Gimbernat (latter part of 18th century), professor at Barcelona (Gimbernat's ligament-ligamentum lacunare BNA). Certain beginnings were now made in the study of the comparative anatomy of the races of man. Pieter Camper (1722-1789), professor at Amsterdam, Franeker, and Groningen, was a widely learned man; at once an anatomist, a zoologist, a geologist, and an artist, he published in almost every branch of natural history essays remarkable for their originality and research. He was the first to show that the hollow bones of birds are connected wdth their respiratory apparatus, and wrote an important memoir on the anatomy of the orang, showing that that animal could not be considered as degenerated from man, as had been supposed by some. Noticing that painters took no pains to depict the special physiognomy of the races of mankind, he began to study racial types and invented the celebrated "facial angle," formed by a plane tangent to the most prominent points of the forehead and face and another drawn through the auditory openings and the ate of the nose. He found that this angle gradually decreases as we descend througli the animal kingdom, and concluded that the different races of mankind might be distinguished by it. A wider examination has shown that this view is incorrect, but the method instituted by him of 336 measuring portions of the skull by means of angles has been extensively used in other directions. Another famous angular measurement was that of the occipital angle of L. J. M. Daubenton (1716-1799) the curator and almost the creator of the splendid museum of the Jardin des Plantes. This was intended to measure the inclination of the foramen magnum which also varies very much in the animal scale, and has relation to the erect position of the body. The comparison of crania was systematically pur- sued by Johann Friedrich Blumenbach (1752-1840) professor at Gottingen, who prescribed for the exam- ination of skulls certain positions that are still in use. He possessed a very large collection of crania, and made important generalizations regarding the races of men. While considering these as very numerous, he grouped them in five principal divisions, to which he applied designations that held for more than a century. Three of these he considered primary: the Caucasian, Mon- golian, and Ethiopian; two secondary or intermediate: the American and Malayan. Logically connected with this, although not devel- oped until early in the nineteenth century, was the curious doctrine widely known as "phrenology," though its founder, Franz Joseph Gall, of Baden (1758-1828), called it "organology." Gall was by no means ignorant of the gross anatomy of the brain, but he knew nothing of its histology and supposed the white substance to be equally active with the gray in intellectual processes. Noticing the conver- gent fibers of the corona radiata, he conceived the idea that the brain was a series of pyramidal "organs'' whose bases were superficial and whose apices were deeply buried in the medulla oblongata. These organs correspond to supposed functions of the mind, concerning which he appears not to have had any well- digested philosophical ideas. He believed that he had demonstrated that the organs varied in size and external prominence in different individuals to such an extent that character and mental aptitudes could be told by palpation of the protuberances of the cranium, due allowance being made for the natu- ral bony prominences common to all skulls. Gall described twenty-seven organs, his pupil Spurzheim added ten more, and his followers in this country increased these by six, making a total of forty-three. When the nerve cells were discovered and it was seen that the gray matter was the effective working element of the brain, and that the surface projecting externally was only a small portion of the cortical area, phrenology had no longer a satisfactory reason for existence as a doctrine. However, it retained a considerable vogue for a time, being especially diffused by peripatetic lecturers whose influence in spreading among the people a knowledge of the physical basis of mind was often considerable. A correct appreciation of some parts of the body was now greatly aided by the advancement of chemistry. Oxygen was discovered by Priestley in 1774. Its true significance was not, however, understood until the demonstrations of Lavoisier (1743-1794), who showed its importance in combustion and respiration. Antoine Francois de Fourcroy (1755-1809) was the first to investigate the composition of organic prod- ucts, and William C. Cruikshank (1745-1800) dis- covered urea. The delimitation of the organs of the body in the living, which may be said to be an anatomical art, was now much advanced by the invention of per- cussion by Joseph Leopold Auenbrugger (1722-1S09), a physician of Vienna. The advances made in the knowledge of the grosser structures were rather refinements upon what was already roughly sketched out than incursions into new fields. Josias Weitbrecht (1702-1747) was the author of a celebrated treatise upon syndesmology that contains the elements of our knowledge of ligaments to-day. Exupere Joseph Bertin (1712- REFEKKNCK HANDBOOK OF THE MEDICAL SCIKNCES Anatomy, History of 1781), an academician of Paris, described the ilio- femoral ligament, the sphenoidal turbinated bones, and the septa of the kidney. Bernhard Siegfried Ubinus (Weiss, 10 { .)7-177(>), professor at Leyden, itly improved myology by the publication of ni'licvni plates showing the muscular system lm ,st carefully delineated. He was also the first to demonstrate by injections the relation between the [at ystems of the mother and the fetus. In the vascular system considerable advances were made. Gilbert Breschet (1784-1845) described the veins and canals of the diploS; William Hunter (1718-1783). brother of John and lecturer at Middle- go pital, demonstrated the arrangement of the lymphatics and showed them to be absorbents. He llso the author of a paper on the anatomy of the id uterus which is the basis of all subsequent descriptions. It particularly notes the changes in the cavity and the formation of the decidua. He care- fully described the descent of the testes, and his name is often coupled with the round ligament of the uterus ami the gubernaculum testis. William Hewson (1739-1774) also contributed to knowledge of the ils and lymphatics, tracing them in birds, 3, and reptiles. Paolo Mascagni (1752—1815) fessor at Siena, Pisa, and Florence, published studies of the lymphatics which were after- ward continued by Vincenz Frohmann (1794-1837), professor at Heidelberg and Louvain. In the realm of the nervous system considerable lines were made. Giovanni Maria Lancisi 1654-1720), the teacher of Morgagni and physician to I he Pope, described more carefully than had been ■ before some features of the brain (nerves of Lancisi = longitudinal striae of corpus callosum). Alexander Monro I. (1097-1767), one of Boerhaave's favorite pupils, professor at Edinburgh, gave an excellent description of the bones and nerves; but his fame was eclipsed by that of his son, Alexander Monro II. (1733-1817), also professor at Edinburgh, who was especially noted for his work in the anatomy > >f the brain (foramen of Monro = foramen inter- ventriculare, sulcus of Monro = sulcus hypothal- amicus). He was the first to attempt a description of all the bursa? mucosae of the body. Felix Vicq d'.Vzyr (174X-1794), an academician of Paris, demon- strator at the Jardin du Roi, and excellently versed in comparative and veterinary anatomy, also studied the brain and added to our knowledge of the minute structure of the white and gray matter (line and bundle of Vicq d'Azyr). Johann Christian Reil 1 1759-1813) first described the insula or island of Reil. Luigi Rolando (1773-1831), professor at Turin, distinguished himself by careful researches in both the brain and spinal cord (fissure, gelatinous sub- stance, and tubercle of Rolando). The cranial nerves received renewed attention. It was Johann Jacob Huber (1707-1778), professor al Gottingen and Cassel, who clearly pointed out the error of Willis in placing the suboccipital nerve among the cranial nerves, though Haller also com- mented upon this. Carl Samuel Andersch (1732- 1777) distinguished from each other for the first time the ninth, tenth, and eleventh nerves, and discovered the petrous ganglion. Samuel Thomas Sommering (1755-1830) is credited with being the first to sepa- rate the facial and the auditory nerves, thus estab- lishing the twelve cranial nerves as we now enumerate them. This enumeration, however, was really first definitely proposed, in 1794, by Johann Christoph Mayer (1747-1801). The little intermediary nerve that makes the tale of the cranial nerves absolutely complete was first described by Heinrich August Wrisberg (1739-1808), professor in Gottingen, who also made other discoveries, his name remaining in the medial cutaneous nerve of the arm, in the cuneiform cartilages of the larynx, and in a small ganglion in the substance of the heart. Vol. I.— 22 Johann Friedrieh Meckel (1721-1771), the In I in a succession of famous anatomists of the name, professor at Berlin, gave especial attention to the trigeminus and facial nerves and was the first to describe the sphenopalatine and submaxillary ganglia and the space in the dura mater that con- tains the semilunar ganglion of the trigeminus. The latter struct ure appears to have been firsl recognized as a ganglion by .1. Lorenz Gasser, of Vienna, about 17"i(l. Meckel had previously described it as a tenia nervosa, and Vieussens as a plexus ganglioni- formis, and Eustachius had figured it in his cele- brated plates. It was named by Hirsch as the gang- lion Gasserianum, in honor of his illustrious master. The tympanic nerve and the superior ganglion of the glosso-pharyngeal nerve were first described by Johann Ehrenritter (about 1775), professor at Vienna, although from the exact researches of L. L. Jacobson (1783-1843), professor at Copenhagen, the nerve usually bears his name. To the latter author is also ascribed the discovery of the vomeronasal organ in the nasal fossa- of the sheep and of its vestiges in man. A physiological discovery of much importance in the elucidation of the anatomy of the nervous system was that of the distinction between the motor and the sensory roots of the spinal nerves made by Georg Pro- chaska, (1749-1S20), professor at Prague. This was afterward clearly established by Magendie (1783- 1855) and by the Edinburgh anatomist, Sir Charles Bell (1774-1S42), who also showed conclusively the motor function of the facial nerve. The long thoracic nerve is often called the external respira- tory nerve of Bell. In the anatomy of the viscera there should be men- tioned the investigations of Lorenz Heister (1083- 1758), professor at Altorf and Helmstadt, who dis- covered the spiral valve in the neck of the gall-bladder; Antoine Ferrein (1693-1709), professor at Paris, who investigated the kidney and the organs of voice; Joseph Lieutaud (1703-1780), who described anew the bladder, mentioning for the first time the trigone. He was famous in pathological anatomy, publishing a work based on the examination of twelve hundred bodies. Johann Nathanael Lieberkiihn (1711-1765) was famous for injected preparations and made some excellent observations on the minute anatomy of the intestinal mucous membrane, including the villi and glands. Johann Christian Rosenmiiller (1771-1820), professor at Leipsic, investigated the nasal fossce and the annexes of the uterus. The anatomy of the vocal organs was also investigated by Denis Dodart (1634-1707), who held that the voice was caused by a vibration of the air in the larynx, while Ferrein held that it was due to a vibration of the vocal chords. Giovanni Domenico Santorini (1081-1737) also paid especial attention to the organs of voice, to the emissary veins of the cranium, and to the muscles of the face (corniculate cartilage of the larynx, emissaria Santorini, musculus riso- rius Santorini of the face). The anatomy of the eye was especially enriched by important discoveries during this period. Francois Pourfour du Petit (1604-1741) paid especial attention to the lens and described the zonular spaces in the suspensory ligament, often called the canal of Petit. Jacob Hovius, a Dutch anatomist (about 1702), appears to have discovered the choriocapillary layer of the chorioid, afterward accredited to Ruysch (tunica Ruyschiana). He also described the vena? vorticosas. Eberhard Jacob von Wachendorff dis- covered the pupillary membrane in 1740, though it is possible that it may have been previously known to Albinos. Jacques Rene 1 Tenon (1724-1816), an academician at Paris, described the fascial attach- ments of the eyeball more accurately than had been heretofore done (capsule of Tenon = fascia bulbi, space of Tenon = interfaseial space). In some cases 337 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES controversies arose as to priority of discovery: the separable posterior elastic layer of the cornea, which was apparently seen and described by Benedict Duddell, an oculist of London in 1729, was rediscovered by Jean Descemet, professor at Paris (1732-1810), and at about the same time by Pierre Demours (1702-1795), demonstrator at the Jardin du Roi. The most important treatise on the anatomy of the eye that appeared during the 18th century, and the basis of all that has since been published, is that of Johann Ciottfried Zinn (1727-1759), professor at Gottingen (zonule of Zinn = ciliary zonule, ligament of Zinn = common tendinous ring of ocular muscles). Felice Font ana (1730-1805), professor at Pisa, described the attachment of the iris and the trabecular tissue since known as the spaces of Fontana (spaces of the angle of the iris BNA). Johann Gottfried Berger (1059-1736) was probably the first to indicate the existence of the orbicular fibers of the iris. The profound and exact researches in the anatomy of the internal ear made by Domenico Cotugno (Cotun- nius, 1736-1822), professor at Naples, were probably the most significant of any made in this region during the century. He also investigated the pathological anatomy of the skin, and was the first to demonstrate by boiling the existence of albumin in urine. His name remains in the liquor of Cotunnius or perilymph, the aqueduct of Cotunnius (aqueductus vestibuli), and the nerve of Cotunnius (nasopalatine nerve). The great advance in the anatomical sciences during the nineteenth century has been primarily due to what may be termed their secularization, that is to say, to the extension of research by placing it in the hands of all students inclined to pursue it. At the beginning of the century the old method of teaching by means of demonstration was still almost every- where pursued. Students were rarely able to dis- sect, and the procuring of bodies for anatomical purposes was beset with difficulties. In 1S27 the University of Edinburgh, with nine hundred students, made dissection compulsory, and this excellent example was immediately followed by London, Liver- pool, and Dublin. In consequence of this the demand for human cadavers was greatly increased and the price so en- hanced that unscrupulous persons were tempted to procure them by surreptitious means. Grave- robbing, hitherto exceptional, now became common, and in every large city where medical schools flourished there became established a set of ruffians who made it their business to supply dissecting tables with bodies ruthlessly torn from the graves to which they had been consigned by sorrowing friends. The large iron cages built over many graves and the for- midable enclosures of cemeteries of this period in England and Scotland testify to a widespread fear, and a glance at the literature of the early part of this century will show what an effect this ghastly practice had upon the popular mind. It would be easy to give many authentic examples which were not confined to disreputable law-breakers; for, led by a youthful love for adventure or perhaps in some cases by a real zeal for knowledge, bands of students and even of professional men broke into cemeteries and violated graves. The law required of medical practi- tioners a competent knowledge of anatomy, and yet denied them the means necessary for attaining it. The absurdity of such a position was not realized until the shocking disclosures of the trial of Burke and Hare at Edinburgh in December, 1828. It was shown that these scoundrels had murdered at least sixteen persons for the purpose of selling their bodies. Similar cases were those of Bishop and Williams, executed in London in 1831. Bishop had followed his nefarious trade for twelve years, and had sold to the colleges at least five hundred bodies, some of which were doubtless those of murdered victims. The excitement occasioned by these trials led to a parliamentary inquiry and the passage of the War- burton anatomy act, August 1, 1832, which legalized dissection under certain restrictions and provided for turning over to the medical schools the bodies of unclaimed paupers. Upon the continent of Europe similar regulations had already been for some time established. The cooperation of a large number of additional workers led to greater precision in all anatomical work, to the accumulation of a vast body of additional facts, and finally to a more comprehensive and satis- factory generalization of the principles that underlie and affect anatomical structure. The idea of the filiation and progressive development of all organic beings — considered a wild and unsubstantial hypothe- sis_ during the eighteenth century — has constantly gained in weight and force by increasing knowledge of existing forms — comparative anatomy; of extinct forms — paleontology; and of individual development — embryology. This increase in knowledge has been greatly aided by improvement in the microscope, which has become an efficient and reliable instrument of research, and by the application of chemical and mechanical methods to the preparation of (is- sues for microscopical examination, which met I: are grouped together under the term of microscopical technology. Fragments from the writings of some of the ancient philosophers, notably Empedocles and Democritus, show that ideas of adaptation and mutability of forms had occurred to them. So, too, we find traces of such speculations in the writers of the last century: Buffon, Erasmus Darwin, and Goethe. These ideas were developed into a coherent system by Jean Lamarck (1774-1829), professor of natural history at the Jardin des Plantes and one of the most acute minds of his age. His force as a naturalist will be appreciated when we recall that we owe to him the division of animals into vertebrates and invertebrates, and also the separation of the groups Crustacea, arachnida, and annelida. He invented the term biology for the sciences of life, though Treviranus suggested it during the same year (1802). In his " Philosophie zoologique" is first scientifically stated and systematically supported the mutability of species and their origin by adaptation. Lamarck thought that such changes were caused mainly by the needs of the animal and the use and disuse of organs, be- coming cumulative in the race by the transmission of acquired characters. For these changes three factors — space, time, and matter — are requisite; and these are produced by nature in unlimited quantities, hence the multiplicity of organic forms. He was the first to conceive the ancestral record of man as a branching tree instead of a series of ascend- ing steps. The formation of the lowest animal from mucilaginous matter was suggested by him, prior to Oken's sea-slime theory. The views of Lamarck, although widely accepted in a modified form by the naturalists of to-day, were very coldly received at that time. This was largely due to the powerful opposition of Georges Cuvier (1769-1832), professor at the Musee d'Histoire Nat- urelle at Paris, and the foremost naturalist of his time. He greatly advanced knowledge of both living and extinct forms of animal life and has been called (he founder of comparative anatomy and of paleontology. From a modern point of view his work is most con- tradictory. While he founded a true natural system in zoology, showing that the forms of the animal world may be reduced to a few distinct types, he yet upheld the absolute fixity of species. While investi- gating fossil remains with an ardor and success never before equalled, he advanced the theory that all organic living forms had been repeatedly wiped out of existence by unexplained cosmic catastrophes. In opposition to the epigenetic views of Wolff and others, he also upheld the evolution of the embryo 338 REFERENCE HANDBOOK OK Till': MEDICAL S< II \< is Anatomy, History nf •om a preformed miniature. Throwing the weight f his great influence against the development theory, e was able, owing to the lack of data, to discredit almost wholly, and to control the trend of biolog- ■al thought, until after the middle of the century. A growing revolt against this domination was, how- ver, caused by the advances of knowledge. Gott- ["reviranus of Bremen t,1777) a remarkable ape-like skull associated with bones of the cave bear; at La Naulette, in Belgium, near Dinant, a fragment of a human jaw of very low type, together with bones of the mammoth and woolly rhinoceros; and in 1886, in the grotto of Spy, bank of the Orneau River, in Belgium, were un- earthed two skeletons associated with similar bones of extinct animals. Other discoveries of like nature were made in Kent, England, near Prague, in Mor- avia, in the Balkan peninsula, in Bohemia, at many places in France, in the pampas of South America and in Patagonia, the latter being associated with the huge carapaces of the glyptodon. The most remarkable find of all was, however, that of Dr. Eugene Dubois, who during explorations in Java (1890-1S95) discovered a fossil skull cap, a femur, and two molar teeth embedded in rock and associated with the remains of extinct animals belonging to the Pliocene epoch. These remains appear to be transi- tion forms between those of the higher apes and the lowest existing men. At the time of Darwin the intimate structure of the cell was little understood or considered, but the re- searches of Oscar Hertwig, van Beneden, Flemming, and man}' others have shown the great importance of this branch of anatomical inquiry, and it is about the problems here found that the principal discus- sions of more recent times have been raised. In 1S66 the lowest form of a cell was considered to be simply a mass of structureless protoplasm endowed with vital properties, the cell membrane and the nucleus having been successively dismissed as non- essential elements. Protoplasm was considered as a homogeneous, semi-fluid substance, with little or no trace of organization, whose chemical constitution was only approximately known, but was believed to I"- highly complex. S • daring spirits ventun d to surmise that it might be possible to produce pro- topla in iii i he chemical laboral ory. The elaborate investigations of recent jreai have shown the futility of such a pretension, indicating that protoplasm has an almost inconceivable insta- bility, that it differs in composition in different o in different parts of the body, and under different stimuli. The substance of which it is composed are among the most complicated known to chemistry, and there is reason t<> suppose that in the living body it is much more unstable than in tlie cadaver. There appears to be a wide distinction to be made between those organic bodies thai an- products of secretion and excretion such as sugar, starch, and urea, and the organi ed bodies such as the different proto- plasms that are produced by the slow and peculiar processes of biotlC growth. The morphological character of protoplasm has also been found to be much more complicated than had been supposed. First granules were observed, then striations, then vacuolizations. The appear- ances being often contradictory and varying much with varying conditions, it is not surprising that they have led to diverse views as to its structure. These are by no means settled as yet, but they may be succinctly grouped as follows: 1. The reticular theory, first brought clearly for- ward by Karl Heitzmann (1830-1896) in 1873, and still maintained, under various modifications, by a great number of cytologists. According to this all protoplasm is composed of two substances: a more solid network — the cytoreticulum or spongioplasm, and a more fluid interstitial substance — the cyto- lymph, hyaloplasma, or enchylema. The granules observed in cells, when not foreign inclusions or masses of dead protoplasm, are the intersections of this network. There is no doubt but that the great majority of cells, when fixed by the usual methods and treated with staining reagents, show some traces of such a reticulum. 2. The filar theory, advocated by Flemming (1887), who by studying cells unaffected by reagents concludes that they are structurally composed of free thread-, the cytomitom, not combined into a reticulum but often containing numerous nodosities. 3. The granular theory, first brought forward by Arndt, and afterward advocated by Altmann (1S87). This supposes protoplasm to be formed of granula- tions embedded in a homogeneous basis substance. These granules, Altmann's bioblasts, are held to be themselves morphological units of a still lower order than the cells. Special means of preparation are required to demonstrate them. 4. The alveolar theory of Biitschli (professor at Heidelberg, 1S89) and his school, who hold that the structure of protoplasm is like that of a fine viscous froth or foam, that is to say, composed of alveoli with extremely thin walls. This structure is be- lieved to be a physical consequence of the peculiar conditions of tension and surface flow possessed by the substance, and may be imitated by emulsions of thickened oil and various salts. This view attempts to explain the appearances of the other theories either by the optical conditions under which the alveoli are viewed or by the reaction of the reagents employed. To demonstrate the alveoli in perfection the protoplasm must be living and the best attain- able optical conditions secured. Under such cir- cumstances they are seen actively to change their forms and relations to each other, these phenomena being so swiftly evanescent that it is impossible accurately to represent them in a camera drawing — ■ while the hand is tracing one part another is rapidly changing. Attempts have been made to reconcile these con- 341 Anatamy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES flirting views. Kolliker considered that the different appearances are due to different states of develop- ment of the protoplasm. In young eells he supposes it to be homogeneous and without strueture, formed of a mixture of various substanres possessing different degrees of contractility and solubility in acids. In such a medium vacuoles will sooner or later appear. If these are numerous and small the structure of the protoplasm will be alveolar; if the walls of the alveoli break it becomes reticular; if the threads of the retic- ulum break it beromes filar. Doubtless this view may assist us in certain interpretations, yet it must be said that recent observations tend to show that even the earliest ovum does not possess a homogene- ous structure. Among the differentations of the protoplasmic mass of the cell the nucleus has been the most sueces- fully investigated. Flemming was the first to show that it contains several substances, one of which, from its affinity for coloring matters, he named chro- matin. The phenomena of indirect cell division (mitosis, karyokinesis) were first connectedly observed by • Anton Schneider in 1873, although Balbiani and others had previously noted separate stages. The nuclear reticulum which plays so important a part in this process was first noticed by Frommann in 1865. The fragmentation of this into separate sec- tions or chromosomes was shown by Balbiani and Carnoy. These again are separable into granular bodies, to which the name of chromomeres has been given by Fol (1891). Other investigators who have greatly advanced the knowledge of this process are Strasburger, Boveri, Oscar and Richard Hertwig, van Beneden, and Rabl. The great advance made in theoretical chemistry by the atomic theory of Dalton (180S) is well known. Although atoms and molecules have never been seen, the hypothetical constitution of bodies supposed to be formed by them is now definitely stated and pre- dirted. The signal success of this theory has led to similar speculations regarding the constitution of pro- toplasm. The first of these was that of Niigeli, who in 18S4 propounded his micellar hypothesis. Accord- ing to this, protoplasm is composed of an immense number of "micellae," elementary units of a crystal- line character, far beyond the limits of microscopic vision. As molecules are formed of atoms, so micellae, units of a next higher order, are formed of molecules. The peculiar physical properties of protoplasm, its imbibition of water, etc., are explained by the arrange- ment and affinities of the micellae. The hypothesis of Nageli has led the way to a num- ber of others of a similar character by De Vries, Wiesner, Haeckel, Hertwig, Roux, and Weismann. These have generally been directed toward explaining by this means the phenomena of heredity. By a series of beautiful experiments (1884) Oscar Hertwig has apparently succeeded in showing that the phys- ical substance upon which this transmission of characters depends is the chromatin found in the cell nucleus. Starting with this for a basis Weismann, in various publications from 1875 to 1894, has propounded an elaborate theory by which he attempts to explain the phenomena of hereditary resemblance. Accord- ing to this, the chromatin is a structure of almost inconceivable architectural complexity. In his sys- tem Weismann, following Nageli, names it "idio- plasm," and supposes it to be composed of groups called "ids," corresponding to the chromomeres seen under the microscope. During the segmentation of the ovum or any other cell division, these ids also divide, so that they are distributed to each cell throughout the body. The ids are themselves com- posed of lesser units called "determinants," because they determine the histological character of the cells within which they dwell. There are as many kinds of determinants as there are parts of the body cap- 342 able of being different. Determinants are themselves compound, being composed of "biophores," or ulti- mate units that control the vital activities of the cell. In the segmentation of the ovum certain of the cells divide so that each division retains exactly similar determinants and thus remains equal in capacity to the original ovum. Such duplicative division pro- duces the tissue denominated "germ plasm" found in the nuclei of the germinal cells of the ovary and testis. Other of the cells divide by a differer, division by which determinants of different kinds are sorted out, grouped together, and relegated to different cells. These are the somatic or body o from which the general tissues of the body are formed. Since the germ cells and body cells separate at the earliest stage, no modification of the latter can affect the germ plasm, hence it is denied that characters ac- quired by the body cells can be transmitted to the off- spring. The arrangement of the determinants by which bodily characters are affected is caused by architect- ural peculiarities inherent in the original ovum and spermatozoon. There is contained within each fecun- dated ovum an entirely closed system of interrelated units that can develop only in a predetermined manner. We have here a reappearance, under a new form, of the theory of preformation sustained by Haller and combated by Wolff. Closely connected with this is His's theory of ger- minal foci (1S74), which supposes that within the protoplasm of the egg the different parts of the adult body are prelocalized and distinct, although not yet formed. To this view many eminent anato- mists and embryologists have adhered, but recent experiments of Hertwig, which show that when the segments of a dividing ovum are shaken apart each may develop into a complete individual, appear to have dissipated these ingeniously devised theories as a puff of wind lays prostrate a house of cards. Among the most ardent and indefatigable investi- gators in the domain of general anatomy during the nineteenth century should be mentioned Jacob Henle (1809-1S85), professor at Zurich, Heidelberg, and finally at Gottingen. He was among the first to realize the importance of the cell theory and did much toward its establishment. He also advanced what may be called the modern theory of pathological processes, holding that they are merely modifications of those of health. Albert von Kolliker (1817-1905), professor at Zurich and Wiirzburg, also had great influence upon research in both general anatomy and embryology. In comparative anatomy should be mentioned Richard Owen (1S04-1892), the author of a curious i theory of the vertebral origin of the skeleton, Thomas H. Huxley (1S25-1S95), who by his writings and researches greatly furthered the doctrine of devel- opment by descent, and Carl Gegenbaur (1826-1908), at Heidelberg, whose researches upon the morphology of the head and limbs are justly famous. In tie paleontological field great advances were made by the discovery in America of fossil deposits of large extent, and of importance far surpassing anything hitherto known. These were especially investigated by Joseph Leidy (1S23-1891), professor in the University of Pennsylvania; by O. C. Marsh (18 1899), professor in Yale University; Edward D. Cope (1840-1S97), professor in the University of Penn- sylvania; Henry F. Osborn (born 1S57), professor in Columbia University; and G. Baur, professor in the University of Chicago. They have thrown great light upon human anatomy by confirming in a striking degree the theories of development and the morphological laws controlling the formation of the human body. The anatomy of the head, of the teeth, and of the vertebral column have been especially elucidated. The advancement of embryology has been greatly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anatomy, History of .icicd by the anatomists whose names have been ilready given, and also by Johannes MUller (1801- S58), professor at Bonn and Berlin, one of the most earned men of his day, who especially studied the levelopment of the genital organs, the glands and he peritoneum; and by Francis M. Balfour (1851- 1882), professor at Cambridge, whose tragic death ,n the Aiguille Blanche of the Alps was a great loss ,i science. An important advance in the establish- nent of the phyletic history of man and other ani- mals was made in 187-1 by Ernst Ilaeckel (born Is:: I), ifessor at Jena, who attempted to show that all mimals possessing a food sac or intestinal cavity descended from a common ancestor (as yet hypo- thetical), the Gastrcea, and that this is represented mbryological development by a stage which may rmed the gastrula, formed by the invagination il the blastodermic vesicle or blastula. This, the elebrated gastrwa theory, aroused violent opposi- tion from the opponents of the development hypoth- n is now quite generally accepted. The details of the intracellular phenomena of the fecundation of the ovum were first observed by Oscar Hertwig in 1N75, in the transparent eggs of the sea urchin. In osteology during the century there should be noted the work of John Goodsir (1S14-1S67) on the structure and development of bone, the discovery of the lacuna? and canaliculi by Purkinje, and that of the osteoblasts by Gegenbaur (1864). William Sharpey (1S02-18S0) did much to increase the knowl- edge of the structure and development of bone, as also did Oilier and Robin in France and H. Muller, Gegenbaur, and Kolliker in Germany. The archi- tecture of the spongy tissue of bones received especial attention from Jeffries Wyman of Harvard University and from H. von Meyer of Zurich. The develop- ment of limbs in vertebrates has been studied by R. Wiedersheim of Freiburg, the form of the skull by R. Virchow of Berlin, and Welcker of Halle, the general morphology of the skull by Gotte of Stras- burg, and Gegenbaur (1SS7). The vertebral column has been investigated by Cunningham of Dublin and Edinburgh, by Merkel and Henke. Arthrology has made important advances in pre- cision and knowledge of the mechanism of joints. Especially worthy of mention are the works of Meyer of Zurich, Braune of Leipsic, Morris of London, Heiberg of Christiania, and Bigelow and Dwight of Boston. Bland Sutton, of London, has investi- gated the nature of ligaments, Bernays, of St. Louis, the development of joints. In myology the minute anatomy of muscle has received particular attention, but cannot yet be said to be settled, as a knowledge of the intimate structure of protoplasm is as yet imperfect. Bowman, in 1M0, was the first to throw any clear light on the subject. He was followed by Leydig and Cohn- heim. Afterward Krause (1S6S) brought forward his theory of "muscle caskets," Hensen showed new details, and Merkel, Engelmann, Rollett, and Ranvier respectively advanced their views. The general morphology of the muscular system has been ad- vanced by the researches of Huxley, Humphry of Cambridge, and Gegenbaur: the study of muscular anomalies has been pursued by Wenzel Gruber, Theile, Wood, Macalister, Struthers, Chudzinsky, Testut, and Ledouble. Special groups of muscles have also received attention, Fiirbringer studying those of the larynx and of the shoulder, von Bardele- ben and Cunningham those of the hand and foot, Ruge those of the face. In the earlier part of the century the structure of the capillaries was not understood, it being believed that they were interstitial lacunae without walls. The demonstration of their independence and continuity was first made by Treviranus in 1836. The endothe- lium of the blood-vessels was first demonstrated by llenle in 18158. Johannes Muller made important discoveries in the vascular system, especially that of the helicine arteries of erectile tissue, in 1835. The study of the formed elements of the blood has greatly advanced, but still leaves much to be desired. The blood platelets (hematoblasts or third corpus- cles) were first discovered by Max Schultze in 1865, and were afterward studied by Bizzozero, Hayem, and Pouchet. Ehrlich (1891) carefully studied the white corpuscles and separated them into varieties that appear to be of great value in pathological anat- omy. Neumann and Malassez have investigated the origin and formation of the red blood corpuscles. Other angiological studies of note are those of His and Bernays on the development of the heart, of Braune on the venous system, and of Bardoleben, Thoma, and Bonnet on the variations in the struct- ure of the vascular walls. Heubner (1872) greatly elucidated the vascular distribution in the brain. A profound study of vascular anomalies has been made by W. Krause. The lymphatics, formerly believed to originate from the interstitial spaces of connective tissue (Ludwig, Brtickc), were shown by Recklinghausen, Kolliker, and Ranvier to form a closed system. The true nature of the lymphatic glands has been elucidated by the labors of His, Klein, Ranvier, and others. Impor- tant investigations into the origin of the lymphatics have been made by P. C. Sappey (1810-1896), professor at Paris, and by Ranvier; in this country by Sabin and Huntington. The connection of the serous cavities of the body with the lymphatic system has been studied by Schweigger-Seidel, Klein, Tour- neux, and Kolossow. The lymphatic tissue of the throat (pharyngeal tonsil, etc.) has been the object of research by Killian, Stohr, Flesch, and others; and von Davidoff and Klatsch have shown that the lym- phoid tissue of the intestine, the mesenteric glands and the spleen are all developed from the intestinal epithe- lium, a conception which Stieda has extended to the thymus gland. Finally Heidenhain has demon- strated the wandering of leucocytes throughout glandular tissues. The convolutions of the brain were thought by the earlier anatomists to be arranged without definite order, being compared to the irregularities of the coils of the small intestine. In 1855 Gratiolet (1815- 1865), by a careful comparative study of the brains of man and animals, showed that the apparently con- fused complexity can be reduced to a comparatively simple plan. This was further developed by Pozzi, Leuret, Ecker, Giacomini, and others. Closely connected with this is the discovery, first made by Broca, that certain motor and sensory activities can be located in definite areas of the cere- bral cortex. He noted that the loss of articulate speech known as aphasia is usually associated with a lesion of the left third frontal convolution (Broca's convolution). This doctrine has been greatly ex- panded by the experiments of Fritsch and Hitzig, Ferrier, Charcot, Horsley, and many others, and has become of great diagnostic value. It will be per- ceived that it only superficially resembles the older doctrine of Gall and Spurzheim. The nerve cells in the brain and spinal cord were probably first mentioned in 1S33 by Christian Gott- fried Ehrenberg (1795-1876), professor at Berlin. They were better described, however, in 1836, both by Gabriel Gustav Valentin (1810-1883), professor at Berne and Johannes Evangelista Purkinje (17S7- 1869), professor at Breslau and Prague, from whom are named the cells or corpuscles of Purkinje in the cerebellum. They were for some time misunderstood, Magendie, in 1839, describing them as infusoria. Their nervous character was established in 1844 by Robert Remak (1S15-1865), professor at Berlin, who at the same time suggested their connection with nerve fibers. 343 Anatomy, History of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The first to note the axis cylinder process or axone of nerve cells appears to have been Rudolph Wagner (1805-1864), professor at Gottingen, but its true nature was first shown by Otto F. K. Deiters (1S34- 1863), professor at Bonn, in 1S65. Although unable to demonstrate its actual continuity with the axis cylinder of a nerve fiber, he gave to the process the name by which it is generally known and also named the protoplasmic processes or dendrites. The con- nection of nerve cells with nerve fibers remained for some time obscure. Counting experiments instituted by Benedict Stilling (1S10-1S79), of Kassel, showed that at the level of the second cervical nerve there are found not more than half the number of fibers that reach the cord by the posterior nerve roots. Since the direct methods of anatomical research failed to resolve the complex architecture of the nervous system, recourse was had to the indirect methods of physiological experimentation, patholog- ical lesions, and embrvological development. In 1S33 Marshall Hall, of London (1790-1857), first clearly demonstrated reflex movements and the in- dependent action of the spinal cord and the medulla oblongata already surmised by Descartes. As early as 1839 Nasse snowed that wdien a nerve is cut its peripheral end degenerates, and in 1S50 this was more carefully studied by Augustus Waller (1S16-1S70), who showed that it is always the end that is detached from the nerve cell that perishes, and that when the posterior root of a spinal nerve is severed between its ganglion and the cord, an area of ascending degenera- tion will ascend to the cord. In 1852 Ludwig Tiirck, of Vienna (1810-187S), showed that a descending degeneration might occur from a lesion of the cord. Following these were similar experiments by Burdach, Goll, Charcot, Vulpian, Kahler and Pick, Gowers, and many others, showing the results of lesions of the brain or cord in producing degenerations. Connected with these are the experiments instituted by Bernhard von Chidden (1824-1886), professor at Munich, which showed that when, in a young animal, a nerve root or nerve tract is torn away or injured, the group of cells with which it is centrally connected suffers atrophy. Among the experimenters in this line of work there may be mentioned Hay em, Forel, and von Monakow. Many investigators had noticed in sections of the brain and cord a difference in coloration between fetal and adult structures which varied with advanc- ing growth. It was Paul Flechsig, of Leipsic, who first showed that this was due to the fact that different groups of fibers develop their myeline sheath at different epochs, and that by this means certain fiber systems can be made out that correspond in general to the results obtained by degenerations. Improvements in technical methods have made this means of research comparatively easy, and such in- vestigations of the nervous system have been carried on by Bechterew, Edinger, Darkschewitch, and others. Observations in the comparative anatomy of the nervous system have also led to important results. In this field should be mentioned the names of Theodor Meynert (1S33-1S92), professor at Vienna; Mathias Duval, professor at Paris; and E. C. Spitzka, professor at New York. By a combination of these methods there was gradually evolved a general idea of the architecture of the central nervous system. This was, however, necessarily somewhat vague and indefinite as long as the minute anatomical relations could not be actually demonstrated. Power to do this was at last obtained by the improvement in technical methods which made it possible to demonstrate the finest ramifi- cations of the nerve cells. Hence arose the neurone theory as advanced by Ramon y Cajal, van Gehuchten, LenhossiSk, and supported by Kolliker and Waldeyer. According to Joseph von Gerlach (1820-1896), the protoplasmic processes of cells unite in a fine anasto- motic network upon which all sensory impressions are discharged and from which, in some mysterious manner, all motor impulses originate. This doctrine was opposed by His (1886) on embryological grounds, by Forel (1887) on pathological grounds. The new methods of staining showed that nerve fibers are merely elongated processes of nerve cells. This led to the conception that the nervous system is composed of histological units (termed neurones by Waldeyer) which may comprise a cell body with its extensions, the protoplasmic processes, the axis-cylinder proc- esses, the nerve fibers, and end organs. These units are held to be substantially independent of each other, never uniting to form a plexus. This view, which has been used with great success to explain the architecture of the nervous system, is now accepted by most histologists. It should be noted, however, that the recent investigations of Apathy (1S97) on the earthworm and leech seem to show that it may require some modification. The internal structure of the body of the nerve o I! has also received much attention and is still under discussion. Remak and Max Schultze considered it fibrillary with interstitial granules. Franz Nissl, by peculiar methods of staining, thinks that he has shown that the structure is not fibrillary, but that two substances exist, one being masses of stainablc granular substance (Nissl bodies, tigroid substance), the other unstainable. He considers that different types of cells exist distinguishable by the arrangement of these substances. The finer anatomy of the organs of special sense is almost wholly the work of the nineteenth century. The development of the eye has been most carefully investigated by Hatschek, Ayers (of Cincinnati), and Kupffer, and the curious discovery was made by Ahlborn (18S6), Rabl-Ruckhard, and Spencer that the pineal body is a vestige of an eye that occurs in some reptiles. The anterior limiting layer of the cornea was discovered by Sir William Bowman (1816- 1892), professor at London; the scleral sinus (canal of Schlemm) was first described by Schlemm (1830), but was previously known to Albinus, as appears from a catalogue of his preparations. The ciliary muscle was first demonstrated as such (in the sheep) by William Clay Wallace, of New York (1835). Bruckc (1S46) and Bowman (1847) afterward described it. Even the deep circular fibers whose discovery is usually ascribed to H. Miiller appear to have been seen by Wallace. The action of the muscle was first correctly described by Helmholtz (1851). A contro- versy of long standing regarding the existence of a dilator muscle of the iris appears to have been settled affirmatively by the researches of Kolliker, Retzius, and Juler. The structure of the lids, the lacrymal apparatus, and the retina was specially studied by H. Miiller (Midler's muscle, Mailer's fibers). The layer of rods and cones (Jacob's mem- brane) was discovered by A. Jacob, of Dublin, in 1S19, the visual purple by Boll in 1876. Recently important comparative studies of the retina have been made by W. Krause and Ramon y Cajal. The complicated anatomy of the ear has been the object of research by a great number of observers, only a few of whom can be mentioned here. The membrana tvmpani has been carefully investigated by O. Shrapnell (1832), Jos. Toynbee (1851), Rudingei (1S67), and Prussak (1868); the anatomy of the auditory ossicles and the mechanism of their move- ments has been elucidated by Helmholtz (1868); the Eustachian tube has been specially studied by Rudinger, Huschke, and Kolliker; the membranous labyrinth by Botteher, Henle, and Hyrtl. The organ of Corti was discovered by the Marchese di Corti in 1851. Additional details of its structure were estab- lished by E. Reissner (1854), M. Claudius (1856). O. Deiters (1S60), and Hensen (1863). Special 344 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anderson Mineral Springs memoirs on the anatomy of the car have been written l,v Ku.liiiH'T, Wharton Jones, Ayers, and Retzius. ' \. in ihc organ of smell, the olfactory cells were described by Max Schultze in 1862, although they were probably seen previously by Ecker and Eckhardt. The tracing of the olfactory fibers has been effected by the labors of Kelliker, van Gehuch- ten and Ram6n v Cajal. The general anatomy oi the passages of the nose has been carefully studied by Zuckerkandl. The taste buds of the tongue were discovered by Schwalbe, of Strasburg. in isii7, and at aliont the same time by Loveh, of Christiania. The tactile corpuscles of the skin were first seen by Meissner and Wagner in 1852, the end bulbs by W. Krause and Kolliker 1 1850- 1858). Pacini discovered the corpuscle's that bear his name in 1836, and they described by Vater somewhat later (1841). Other nerve endings recently described are those of Golgi in tendons (1878), those of Ruffini in the fingers (1893), and the "muscle spindles" of Kiihne and others found in the substance of muscle. Most of our accurate knowledge of the minute iv of the viscera was developed during the nineteenth century. Space does not permit a detailed account of the discoveries, but mention lid be made of the work of Neumann, Lent, and Rose upon the teeth, and the attempts of Ryder, iorn, Cope, and others to obtain from paleonto- logical and other evidence a connected account of the mechanics of their development; of the work of Flemming, of Kiel, upon the principles of gland con- struction; and that of Heidenhain of Breslau upon the anatomy of the pancreas, the salivary and peptic glands." Investigations of the development of the peritoneum by Toldt, His, Treves, Brosike, and others have greatly aided our comprehension of that plicated structure. The liver has been specially investigated by Kiernan, Hering, Heidenhain, and Kanvier, and in the anatomy of the kidney great advances have been made. Henle described the loops of the uriniferous tubules that bear his name in 1862, Ludwig and Heidenhain have done much in elucidating the structure of the tubules, and Disse has studied the changes of the epithelia during tion. In the generative organs of the male researches in spermatogenesis have been carried on by La Valette St. George, Nussbaum, Flemming, Hermann, and Minot. In the female organs Pfliiger and Waldeyer have investigated the structure of the ovary and the development of ovules, and Nagel has given the first exact description of the human ovum. The situation of the pelvic organs has been carefully determined by B. Schultze and Waldeyer, and an exhaustive exami- nation of the human placenta has been made by Minot. Frank Baker. Anderson Mineral Springs. — Lake County, Cali- fornia. Location. — Twenty-one miles from Calistoga, five miles from Middletown, and ten miles from the Great Geysers. Access. — By stage from Calistoga and Clovendale. The worshipper at nature's shrine, the lover of grand and varied scenery, will find all that can be desired at the Anderson Mineral Springs. The mountain stage ride is one of the most picturesque in the State. The ever-changing picture of hill and dale, of forest and shrubbery, and of brooks with ferns and mosses forms one of those pleasing pano- ramas which the spectator loves to recall in after days. The springs with the hotel and cottages are located in a cosy nook in a large canon surrounded by forests abounding in picturesque waterfalls. The cool, leafy dells and the profound silence and solitude of the dense forests form an ideal combination to at I ract the early morning rambler. The atmosphere hen' is balmy and exhilarating and free from humidity. Fish and game abound all the year round. The accomi lations offered to guests are excellent, and \ isitors come by the thousand to enjoy the numerous advantages of the spot. There are nine important springs. The principal drinking-spring, known as the Cold Sulphur, is located about 250 yards from the hotel. It »;e .-.nil.. I'd ic 1 1; n ,: :.. and found by him to have the following composition: One United States Gallon Contains: Solids. Grains. Sodium chloride. 1 -09 Sodium carbonate. . '' -'' Sodium sulphate 6. 18 Potassium salts Traces. Magnesium carbonate 11 .73 Magnesium Bulphate 16.95 I 1 1, i inn carbonate 20.40 Calcium sulphate 9.10 Ferrous carbonate 0.46 Arsenious salts Traces. Silica 2.45 Organic matter Traces. Total 77 . 03 Cub. in, P , f Carbonic acid gas 243 50 aseS I Sulphurated hydrogen 4-20 This may be characterized as a saline sulpho- carbonated water. It has been found very beneficial in chronic skin diseases of strumous and syphilitic origin. In liver, stomach, kidney, and bowel troubles, in uterine and ovarian engorgement, and in glandular congestions, the water has also proved to be of much value. It is aperient, diuretic, and alterative in its action. The "Sour Spring" is one of the few California mineral springs containing free sulphuric acid. Its sour taste was formerly supposed to be due to alum, but the following analysis by Mr. George E. Colby, of the California State University (1889), shows that no alum is present: One United States Gallon Contains: Solids. Grains. Sodium chloride . 08 Sodium sulphate . 49 Potassium sulphate ®'„ Magnesium sulphate 4.76 Calcium sulphate 2.07 Ferric sulphate . 63 Aluminum sulphate* 7.11 Boric acid (with spectroscope) Strong test. Lithium (with spectroscope) Well-marked test. Ammonia (manganous sulphate) . 33 Silica 3 - 94 Organic matter Traces. Total 20.28 A considerable quantity of free sulphuric acid was also revealed by the analysis. The temperature of the water is 64.3° F. It possesses tonic, astringent, and gently laxative properties, and has proved bene- ficial in hemorrhages from the lungs, menorrhagia, and dyspepsia. . Another valuable water is the " Iron Spring. 1 he following is Mr. Colby's analysis, made in 1S99: * A microscopic examination of the residue obtained by slow evaporation fails to show characteristic crystals of alum. 345 Anderson Mineral Springs REFERENCE HANDBOOK OF THE MEDICAL SCIENCES One United States Gallon Contains: Solids. Grains. Sodium chloride 0.18 Sodium bicarbonate 0. 19 Sodium sulphate 3.42 Potassium sulphate 1 . 17 Maunesium sulphate 7.36 Calcium sulphate 10.88 Calcium phosphate 0.15 Ferrous carbonate 1.18 Alumina 0.93 Boric acid (with spectroscope) Strong test. Lithium (with spectroscope) Well-marked test. Manganous carbonate 177 Silica 4 . 22 Organic matter Small quantity. Total 31.45 Free carbonic acid gas, 25. SO cubic inches. Temperature of water, 124° F. This is a mild calcic-chalybeate water. It possesses tonic and slightly laxative properties, and is useful in anemia and chlorosis and in conditions requiring restorative agents. Among other valuable springs in this group may be mentioned the "Cosmopolitan," an excellent drinking water, but possessing slightly laxative properties; the "Bellmer" Spring, a light saline-sulphur water; the "Magnesia Spring" (known also as "Father Joseph's Spring"), a rich saline water having valuable laxative properties; and the "Hot Sulphur and Iron" or bath- ing spring. These last waters have a temperature of 14.5.5° F., and have been found very beneficial in rheu- matism, chronic joint swellings, constipation, and skin diseases. It is claimed that the inhalation of the hot sulphurous steam of- this water is highly useful in cases of chronic bronchitis, incipient phthisis, and catarrhal affections of the nose and throat. There are good facili- ties for bathing. The incrustations formed by the hot sulphurous vapors on the surrounding rocks are gathered and powdered and used in cases of chronic nasal catarrh, as well as for acute coryza and phar- yngitis. This powder represents all of the solid mineral ingredients found in the water. The pine forests, elevation, and climate are of undoubted value in many subacute and chronic diseases. Emma E. Walker. Andral, Gabriel. — Born in Paris, France, on Novem- ber C, 1797. He took his medical degree in 1821. In 1830 he was made Professor of Internal Pathology at the Faculty de M<§decine; and in 1839 he accepted, as the successor of Broussais, the Chair of General Pathology and Therapeutics. He performed the duties of the latter professorship, during a period of twenty-seven years, with such distinction that he was spoken of on all sides as one of the celebrities of French medicine. He was also one of the attending physicians of La Charity Hospital. In 1S66 An- dral retired from practice and from his professorial duties. He died on February 13, 1S76. Andral 's lectures were characterized by the ex- traordinary clearness with which he described all the phenomena of disease; and this same characteristic will be found to exist in his published writings. Of these the two most celebrated are: "Clinique Medieale," Paris, 1823-1S27, five volumes; and "Traite d'Anatomie Pathologique," Paris, 1X29, three volumes. A. H. B. Andre, Nicholas. — Born in Dijon, France, October 15, 1704. He practised for years in Paris and vicinity, serving as surgeon to the Maison royale de Saint-Cyr and as charity surgeon to the parish of Versailles. His chief claim for recognition rests upon the fact that he invented urethral bougies. Trea- 346 Uses published: "Dissertation sur les maladies de l'uretre qui ont besoin de bougies"; "Observations pratiques sur les maladies de l'uretre, et sur plusieurs faits convulsifs, et la gudrison de plusieurs maladies chirurgieales, avec la composition d'un remede propre a r ^:--: • -> ■,*-♦■ • ! Wt--'. i> •• m Fig. 198. — The Spinal Cord from a Case of Pernicious Anemia, Showing the Microscopic Appearances of the Gray Mutter in the Section Shown in Fig. 197. The small veins are surrounded by distended perivascular spaces and one of them is filled by a recent thrombus. The word "febrile" it will be remembered was in- corporated into one of the many descriptive names given this disease. It is well to remember that fever is not an uncommon associate of the more advanced stages of pernicious anemia. It is impossible to state any symptom-complex, even in the fairly well ad- vanced stage of the disease. The important point, here, then, is that many other conditions are suspected before pernicious anemia is thought of. This can- not be emphasized too strongly — a heart lesion or nephritis or both, in the majority of cases, are thought to be the real malady. Perhaps there are two reasons for this — first, because of the signs pointing to both the heart and the kidneys, and second, because it is hard for the physician to believe that one can walk about with a blood count of two and one-half million 349 Anemia, Pernicious REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cells. The asthenia is usually taken to mean cardiac incompetency but it is often the only symptom of a profound toxemia with a red cell count of a little over 2,000,000 and the physician is thrown off the right track by the fact that the patient "walked in." This feature of the disease is probably due to the fact that the destructive process has worked grad- ually. A healthy individual whose blood is re- duced suddenly by hemorrhage to 2,000,000 is pros- trated. Here is another evidence that the disease is of long standing before symptoms develop. It per- haps also shows that the reserve power of the blood, like that of many other organs, is considerable. Though there are symptoms in the advanced cases pointing to the heart (palpitation, dyspnea), these are not as marked as in primary cardiac disease, because the patient with pernicious anemia rarely attempts violent physical effort. .Some patients become very irritable and being unwilling to seek medical aid as they "feel perfectly well," it is through a member of the family that the report of this irritability reaches Fig. 199. — The Spinal Cord from a Case of Pernicious Anemia, Showing Combined Degeneration of the Posterior and Lateral Tracts. The direct pyramidal tracts are also considerably degene- rated. the physician. This indefinite group then com- pletes the symptoms of the early and advanced stage. Vertigo, headache, numbness and tingling of the extremities may be complained of, and in the late stage of the disease symptoms referable to the lo- comotor apparatus may be present. The patient may stagger slightly, the Romberg symptom being present in some cases, so that tabes and multiple sclero- sis are diagnosed without the blood condition being suspected. Such cases have had the diagnosis of pernicious anemia made at autopsy only. Hemor- rhage from the nose and other mucous membranes is not common. Even at the late stage asthenia stands out as the distinctive feature but this, like many of the associated symptoms, is quite compatible with other suspected pathological conditions, especially cardiac and renal disease. Perhaps a distinctive feature is to be found in the fact that these people even after or during a second or third paroxysm of profound anemia often insist upon continuing at work or business and declare they "feel quite well." This is unlike the cardiac or renal case. There are then no symptoms peculiar to pernicious anemia. Physical Signs. Early Stage. — As with symptoms we know practically nothing definitely of the early signs of pernicious anemia. Advanced Stage. — When, however, the patient begins to fail he seeks medical aid. This may be during one of the paroxysms of profound blood defici- ency, at which period a positive diagnosis can be made by the blood picture. If, however, the patient is seen between such paroxysms he may present fea- tures of a secondary anemia, such as occurs from any of the common causes — neoplasm, nephritis, cardiac disease, etc. The retention or excess of fat will be an important sign. The patient looks ill — very ill — yet he is fat; the fat can often be picked up from the abdomen in thick folds. The shoulders, the thighs, and the hips are well rounded out with fat. There may be small aggregations of fat in the abdominal wall and about the back and neck, which might be mistaken for metastases from a malignant growth. A wasting disease (especially portal cirrhosis) in those who have been obese but who are beginning to lose flesh, will sometimes present this appearance of fatness, but such cases usually show the lineae atrophica? in the skin of the hips and shoulders and axilke, due to the loss of the underlying fat. Pernicious anemia patients are well rounded out with fat even at death. This point has not been sufficiently emphasized in the clinical description of this disease. In marked con- trast with this plump body is the yellow white color, which gives at once the impression that the individual is ill; the yellow tinge may be detected in the con- junetme and by pressing a glass slide upon the lips. The appearance is not, as a rule, that of jaundice; one must look closely for the yellow color, compare it with a normal skin, and so convince himself that it is not the dough white of chronic Bright's, the brown white of cachexia, or the light yellow of hepatic disease. The blue veins stand out markedly in the yellow white skin; the conjunctiva? as mentioned above show a light yellow tinge, this differing from the blue white sclera of chlorosis which resembles the white of a hard-boiled egg. The conjunctiva; in chronic Bright's have a pearly whiteness and do not show any yellow tinge. A fairly plump but ill-looking individual with a yellow white skin, slightly yellow tinged conjunctiva, complaining of an undefined sense of weakness, but who is able to walk about and insists on continuing with his business (provided this does not involve more than ordinary physical effort) is one in whom pernicious anemia should be strongly suspected. It is between paroxysms, when the blood picture is not typical, that these clinical features are of great value in detecting pernicious anemia. The heart examination reveals very little or no displacement of the impulse or enlargement of the heart, but the systolic thrust may be rather widely distributed and fairly forcible. The blood pressure is exceptionally low. At times there may be an acceleration and slight irregularity of the heart. The systolic impulse may be quite marked at the base of the heart and in the arteries of the neck. The jugu- lar pulsations are visible but are not systolic in time (negative pulsation). This combination of pulsa- tions requires careful analysis — at times with the sphygmograph — in order that very misleading con- clusions be not accepted. Their explanation has been set forth by many observers, but neither experimental nor postmortem findings have placed these explana- tions beyond the realm of theory. To one not familiar with the blood in this disease it might be inferred that a blood examination would at once settle the diagnosis. The whole blood picture will be discussed later, but it is well to state here that all the foregoing symptoms and signs may be present and yet the blood present a reduction only in the hemoglobin and red cells, an irregularity in size and shape and a high color index and possibly an increase in the small mononuclear cells. In other words, the blood, if seen between the paroxysms of profound anemia, is by no means distinctive. The high color index and the increased small mononuclear percentage would be in favor of the diagnosis of pernicious anemia, and should prompt the physician to keep the patient under close observation. The paroxysmal character of the blood changes in this disease is frequently over- looked and cannot be too emphatically insisted upon. 350 REFERENCE HAXDBOOK OF THE MEDICAL SCIENCES Anemia, Pernicious \ systolic murmur is usually hoard along the .sternum, ,i the apex or above the clavicU — often at all these es with equal intensity. Diastolic murmurs are r ,l,.,l, but their cause is a matter of surmise a no ms postmortem have been found to account o. Extreme dilatation is rare and tricuspid insufficiency is uncommon. It will be seen that the physician could very res son ably take the dyspnea and asthenia to mean a failing compensation in a heart too damaged to produce e\ i- dence of valve lesion. Cases of pernicious anemia are frequently sent to the hospital with this diagno lungs with the exception of an occasional pleural effusion are negative. The liver may be just palpable, spleen is usually not palpable. The urine is usually pale, normal in quantity, varying in specific gravity, and shows serum albumin, distinct trace, with finely granular and hyaline casts. Examination of the eye-grounds may reveal large hemorrhagic 3 (flame spots) though personally I have not seen these except in the far advanced cases. In fact hem- orrhages (petechias, epistaxis, etc.) are not common until very late in the disease, then they may be exten- sive and occur on any of the serous or mucous sur- 3, This, together with slight edema of the extrem- (usually legs, but sometimes hands, very rarely face) and occasionally the serous effusions above referred to and the signs in the heart almost uniformly to ih" overlooking of the blood condition. If pallor of the skin has been noted by the physician he is apt to dismiss this with the statement "second- ary anemia." It is well to emphasize this, for scarcely a year passes in a hospital service without the cardial'. renal, or, as will be seen presently, the nervous signs and symptoms masking the blood condition and deferring the diagnosis to a week or more after the patient's admission and even till his autopsy, as not Infrequently occurs, when the nervous symptoms have been those most evident. In the gastrointestinal tract the absence of hydro- chloric acid (achvlia) in the gastric contents is an early and fairly constant finding. This occurs with- out 'reference to the symptoms and its significance i< by no means understood. One is tempted into theoretical explanations which are without foundation in clinical, experimental, or postmortem evidence \s a clinical sign, in pernicious anemia, it is very con- i. but with regard to the stage or severity of the disease it vields us no information. The changes in the nervous system (spinal cord) have been so constant that some writers have incor- porated these into a definition of the disease. In the ion on pathology in this article will be found photographs of sections of the cord illustrating the histological changes which occur. At what stage in the disease these changes occur is difficult to deter- mine. Clinical manifestations are very variable. The tingling and numbness observed early have been attributed to the action of toxins upon the cord. There may be paresthesias and spastic paraplegia and signs of multiple sclerosis and of tabes, the two latter diagnoses being made at times without pernicious niia being discovered till autopsy. There may aNo lie practically no neurological features clinically, vet extensive cord destruction be found at autopsy. That these cord lesions cannot be produced by ischemia alone seems proven. It is therefore reason- able to conclude that the destruction is rather the result of a toxemia than of an anemia, and that the cord, like the blood and other tissues, is a victim in the general destruction. In the late stage of the disease these neurological features may eclipse all others and the case may go to autopsy as exclusively a tabes, a multiple or lateral sclerosis, etc. Neurological features being present or absent and the diagnosis of pernicious anemia having been made, there may develop slight delirium but the asthenia is now so profound that this i> never active. The patient usually sinks into coma, in which he may remain for two or three days when death takes place. There are no complications of this di \ny feature such as hemorrhage, eord lesions, etc., which might lie considered a- a complication is attributed to the hemolytic and toxic action of the undiscovi poison assumed to be the active agent in the di • Relapses and Duration. — A most important feature of the disease is « tendency t" improvement with subsequent relapses. The number of relapse i patient may go through would appear to be limited in the majority of eases to three. After two ysms of profound anemia, one has grave doubts re- garding the outcome of the third. These may be spread over one year or five, seven, or ten years. I have seen no case last beyond five years. When a patient dies, apparently in the first paroxysm, it is difficult to say whether he has not "worked through" former attack's without consulting a physician. The blood changes during and between these attacks will be now considered. The Peripheral Blood. — (For a study of the bone marrow see "The Bone Marrow" under "Pathology" in this Article, p. 347.) An individual presenting some or all of the above symptoms and signs may be in one of several degrees of blood destruction when the physi- cian sees him. The most distinctive of these are the following: I. / ,ind Interparoxysmal Stage. — Moderate reduction of hemoglobin (oligochromemia) and red blood cells (oligocythemia) (3,500,000). Color index high. Variations in size and shape (anisocytosis) of the red blood cells. Variations in the intensity of the staining of the red blood cells (polychromatophilia). Increase in the percentage of small mononuclears i lymphocytosis). ; 1904 Sept. Oct. Nov. I>ec. G s 15 17 23 3 Hi 22 1 11 1 I - :.<■■ ."■ , tT ,-,. . 1 - ft s.non.«X> •■ » J ■■ ■- *■■ * '■* - A. 1 - -FT -*- -rf 1 1 J — \ H^MOGl-OBllC RED CORPUSCLES: WHITE COHPUSCLES- Fig. 200. — The Blood Chart of a Case of Pernicious Anemia as Observed in 1904. The highest lymphocyte count (October 3 1904) was 37 per cent., with a polynuclear neutrophile count, on the same date, of 55.6 per cent, ' Normoblasts were usually present; and reached 34 in a slide on October 10, 1904. At this time 9 meftaloblasts were also found, but thereafter nucleated red cells were not seen. See subsequent findings on Fig. 201. II. Anteparoxysmal and Postparoxysmal Stage (shortly before "and shortly after a paroxysm). — Oli- gocythemia and oligochromemia marked (2,500,000). Red cells appear deeply stained. High color index. Anisocytosis. Lymphocytosis. Polychromatophilia. i Iccasional nucleated red cells (normoblasts). III. Paroxysmal Stage. — Oligocythemia and oligo- chromemia profound (1,500,000). Color index high. Anisocytosis. Ervthroblasts numerous. Normoblasts and large nucleated red cells (megaloblasts) present. Karyokinetic figures may be seen. IV. Profound Degree of Paroxysmal Stage. Such as usually precedes a fatal termination. — Oligocy- 351 Anemia, Pernicious REFERENCE HANDBOOK OF THE MEDCAL SCIENCES themia profound (1,000,000 or less). Oligochromemia; hemoglobin may be too low to estimate. High color index. Anisocytosis marked, stippling. Polychro- matophilia. Erythroblasts often entirely absent. Megaloblasts may be present. Free nuclei may be present. Lymphocytosis. If a case, presenting either I or II, be carefully £ Jon. Feb. Mar. Apr. May I -3 \ HIT- Sept. Oct. Nov. 13 'JO j: ::i 3 10 17 24 4 id is 24 4 11* Jl ::o 17 - 25 2 c i -j is 2 hi 21 27 - is 22 II u» I 1 "- •j;. y> MP :;> To ...-, -/ ' , / T " ;.:, I ,-.o V^ / f > 3o ^ s \ ■■ s 28 s 1.0U:U"KX) 1 . _UJ. Lfj ft i 1.000 ~^:7" """ 0.OOO (.'hill (),-■„, 0.00(1 *.o«i — - 2. Off] -"l " s. 1 H/CMOGLOEIN: RED CORPUSCLES; Fig 201 — The Blood Chart in same Case (as shown in Fig. 200) in 1909. The highest lympho- cyte count was 43 per cent. (July 25, 1909) ; the polynuclear neutrophile count, at the same time, was 38 per cent. Nucleated red cells were a constant feature, megaloblasts preponderating. followed, sooner or later a paroxysm will occur and III will be observed. Figures 200 and 201 show the blood course of a case over a period of five years. The clinical error is in failing to follow carefully the case which presents the apparently unimportant anemia seen in I. In I, the high color index, the anisocyto- sis and the lymphocytosis should arouse suspicion of pernicious anemia. Myelocytes may occur at any stage, but there is nothing significant in their presence. The blood plates are said to be increased, but this is not a constant finding. From what has been said and from these charts it will be seen that the diagnosis is not to be made upon the presence of nucleated red cells alone. This must be emphasized, for cases of pernicious anemia are frequently overlooked during the in- tervals between paroxysms because the physician considers the erythroblast an essential feature of the blood of pernicious anemia. Under what circumstances then are nucleated red cells present or absent in pernicious anemia? Nucleated cells may be entirely absent in: (1) The interparox- ysmal period. (2) The latter part of a parox3'siii, when the blood has increased one to two million cells. (3) The early or mild paroxysms. (4) The graver stages of the disease and in the later paroxysms; in these stages the erythrogenetic centers would seem to have been overwhelmed. It is well to warn against a poor nuclear stain which fails to bring out the nuclei, thus giving the impression of no nucleated red cells. The nuclei of the white cells will show whether or not such a stain has been used. Lymphocytes may be mis- taken for erythroblasts. (See also below.) Nu- cleated red cells are usually present: (1) During the gravity of the paroxysm; in the profound stages the megaloblast preponderates; as the red blood count begins to rise the normoblast usually preponderates. (2) At the beginning of the parox- ysm. 352 It will therefore be seen that the characteristic features of the blood in pernicious anemia are: 1. Red cell reduction (oligocythemia) constant. 2. Hemoglobin reduction (oligochromemia) constant. 3. High color index constant. • 4. Nucleated red cells (erythroblasts), gigantoblasts, megaloblasts, normoblasts, microblasts inconstant. 5. Anisocytosis, giganto- cytes, mcgalocytes, normo- cytes, microcytes, poikilocytee constant. 6. Polychromatophilia in- constant. 7. Normal or low white count constant. 8. Deep staining inconstant. 9. Stippling inconstant. The nucleated red cell, if present, may be an expression of the stage and severity of the disease but never an essi «- Hal feature on which to base the diagnosis. One may go further and say that though the nucleated red cells may be present, unless the other char- acteristics above enumerated white corpuscles .. are also present the diagnosis, pernicious anemia, cannot be made. Nucleated red cells, then, are distinctive of a grave anemia only. To determine the type of the anemia in which such cells are found the other clinical and blood features of the case must be taken into account. The small lymphocytes may be mistaken for a nucleated red cell. It is some- times quite difficult to determine, certainly, which cell one is dealing with, but it is safer to decide iu favor of the leucocyte. The karyokinetic figures seen n the red cell nuclei are of more interest at present to the hematologist and the biologist than to the clinician. s 190? & ll>08 May June July Aug. Dei,. Jan. Feb. Ma* r. u •Ji ;;o 11 is 2C :: 11 is 25 :i i; 10 13 Ill HI Hi 17 31 i; 14 22 2 s G ion -..o «. I -* ; 'r / j* , — A ■ z: — -. . * ; " ::■ ^ T -" . *~ - V^ *. *\ \ ! : 1 i 1 H/EMOGLODIh:. RED CORPUSCLES - - WHITE CQREUSCLES — Fig. 202. — The Blood Chart of a Case of Pernicious Anemia. The microscopic examination was typical of pernicious anemia. The highest lymphocyte count was 58 per cent. (July 18) ; the polynuclear neutrophile count on the same date was 25 per cent. A strking feature was* the absence, for the most part, of megaloblasts. Normoblasts were constantly observed, although not in great numbers. In September, 1909, this case developed marked neurological symp- toms and was treated exclusively in his final illness for these. Pernicious anemia was detected at autopsy and his early record (given here) in an other hospital was looked up. He died December, 1909, in his third paroxysm (probably). This is true also of the extruding and free nuclei. I have never found free nuclei without nucleated red cells as well. The stippling, polychromatophilia, and deep staining of the red cells are important but not constant features. The blood crisis occasionally occurs in this disease. Within a few hours there may be a shower of nucleated REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anemia, Pernicious red cells, mostly normoblasts. The striking point aboul this crisis is the sudden appearance and dis- earance of these cells in the periphereal blood. es, as described by \ on Noorden in 1891 , are ,, n also after profound hemorrhage from traumatic other causes. There are many theories regarding the phenomenon, but as yet none of these is sup- ported by substantial evidence. It is important to remember thai : 1. Pernicious anemia may occur without nucleated ills. 2. Nucleated red cells occur more commonly in this than in any other anemia. ,:. Nucleated cells occur in other diseases than pernicious anemia. I. rhe normoblast is the commoner of the nucleated red cells and its presence either in excess of or to the exclusion of megaloblasts warrants a better osis. 5. The presence of many gigantoblasts and me- galoblasts is of grave significance. ii. Nucleated red cells occur in showers, which may appear and disappear suddenly.* 7. The presence of megaloblasts is strong evidence of pernicious anemia, but must be taken together with other blood features. s. Small mononuclears may be mistaken by ex- perienced observers for nucleated red cells. Diagnosis. — The diagnosis has been considered to a large extent in describing the blood picture. ere are a few conditions, however, which should be cially mentioned here, namely: (1) Secondary anemia, especially in the profound stages: (2) Unci- naria anemia (uncinariasis, hookworm disease, anky- lostomiasis); (3) dibothriocephalus anemia. 1. Secondary Anemia. — One should remember that it is generally admitted that a toxin is the factor in the causation of all anemias, barring only that due to traumatic hemorrhage, which might be considered in a class by itself. So far as we know the most destructive of such toxins is that associated with pernicious anemia. It therefore is a matter largely of degree of destruction, when comparing the anemias, as is the case when considering purpura. Occasion- ally an anemia due to the toxin of a known disease, nephritis, carcinoma, portal cirrhosis, tuberculosis, etc., will reach a stage when the erythrogenetic areas would seem to fail to respond to the demand for new cells and the blood features of pernicious anemia will begin to appear. Rarely, however, is the picture identical and certainly never is this so in the early stage. The ravages of the primary disease will usually have manifested themselves by the time the blood takes on the features of pernicious anemia. Oligocythemia and oligochromemia are rarely as pro- found and the color index is rarely above O.S and usually about 0.5. Polynuclear leucocytosis is com- mon and there is a greater tendency to poikilocytosis than to variation in size. That is, megalocytes and macrocytes are uncommon. It must be remembered that nucleated red cells may be found in the severer M;iges of secondary anemia and that the cell most commonly found is the normoblast. Perhaps the most important differential feature is the absence, in secondary anemia, of a paroxysmal tendency. The anemia may be profound, but- is more apt to have become so after long periods of stationary character- istics in which there has been no disposition to im- provement. The person presenting the emaciation * Export hematologists may observe a blood and report no nu- cleated red cells in a specimen in which a house officer will find many such cells. Each may be quite correct owing to the "show- ering" tendency of the normoblasts. It is well, however, to uric such a blood as soon as possible after such an erythro- blastic finding is reported, in order to determine whether lympho- have been mistaken for red cells. "As soon as possible" beca i nil "showers" may soon "clear up" and the finding remain in permanent doubt. Vol. I.— 23 and cachexia of Secondary anemia appeal ii) marked contrast to the one with pernicious anemia who is plump and well rounded out with fat even to death. When the blood shows characteristics Buggestive of pernicious anemia and no primary factor is evident these features should be carefully considered and a thorough search made for .in obscure parasitic or septic agent. It all the clinical features be carefully Considered it will be rare to find that secondary or symptomatic anemia presents characteristics identical with those of pernicious i \ddi onian) anemia. Exceptions to this statement are the following: 2. Uncinariasis (Hookworm, I ' urimirin il,m,/, ,,,,!,. , Ankylostoma duodenale).^M\ that has been said re- garding pernicious anemia is applicable to the ad- vanced stage of the anemia associated with this parasitl — the only difference being the presence of ova in the feces, .-i low color index, and a tendency toward an eosinophilic leucocytosis. For further in- formation on this important subject the reader is referred to the article with this title in the Reference Handbook and 1'.. K. Ashford's excellent monograph published by the I". S. Government. 3. Bothriocephalus lotus. — Except in the early stage of the anemia, (chlorotic stage) caused by this worm, the blood is identical with that seen in perni- cious anemia. The finding of ova in the stools there- fore constitutes the differential feature. The blood of children up to six or eight years of age presents many variations and one must make careful clinical observation upon a child whose blood shows oligocythemia, oligochromemia, or a leucocytosis, for such variations may be compatible with a temporary reaction to some slight physiological disturbance. Megalocytes, erythroblasts, and myelocytes may appear in children with moderate anemia. Well authenticated cases of pernicious anemia are unknown in infancy, extremely rare in childhood, and uncommon before the age of thirty and after the age of fifty. Prognosis. — Among the 1,200 cases collected from literature, including his own case reports, Cabot finds but six recoveries, taking " six years free from trouble" as the criterion upon which to base an assumption of cure. While these statements indicate a great mortality they show also that, as Hunter strongly maintains, the disease is not invariably fatal. See section on Relapse and Duration for further con- sideration of the prognosis. Treatment. — Although the physician is helpless before this destructive condition there are one or two warnings which can with great advantage be given. During the intervals between paroxysms, even though the patient feels energetic and is impatient to be at work, every effort should be made to conserve the energies. Journeys, sight seeing, long hours at business, exacting work should at these times be emphatically forbidden. Travel is not infrequently prescribed to the business man who is in the stage of remission of a pernicious anemia, and subsequent events will lay the physician open to severe and just criticism for giving such advice. It must be remem- bered that these people, as though impelled by some stimulant in the system, are difficult to restrain, not from hard labor, but from considerable activity. Hunter's teaching that oral and gastrointestinal sepsis is largely responsible for the toxemia has sug- gested intestinal irrigations in an effort to reduce absorption of any possible toxin from this source. The condition of the teeth should be repeatedly and thoroughly looked into. A minimum of protein in the diet has been recommended, but it is not clear that this has any importance one way or another. The only drug employed is arsenic and no one preparation seems superior to another, and adminis- tration by mouth seems quite as efficacious as by hypodermic injection. It is most commonly given as Fowler's solution or in pill form, the dose of the 353 Anemia, Pernicious REFERENCE HANDBOOK OF THE MEDICAL SCIENCES former being gradually increased from two to three minims thrice daily to fifteen or twenty thrice daily. Physiological effects should be carefully looked for and the dose reduced accordingly. Manj T other measures might be mentioned but so far experience offers nothing in their support. C. N. B. Camac. References. 1. "On the Constitutional and Local Effects of Disease of the renal Capsules," by Thomas Addison, 1855. _'. "Correspondenzblatt f. Schweizer Aerzte, Biermer, 1872. 3. Lack of space admits of no more references being given. In Vol. v. of Allbutt and Rolieston's System of Medicine (1009) will be found a full bibliography. Addison's (1855) and Riermer's (1872) Monographs, to which reference is given above, mark the beginning of a clinical recognition of this important disease. Anemia, Secondary. — Anemia might literally be assumed to refer to diminution of the amount of blood, but actual^ it is made to refer to diminution or deterioration in the erythrocytes, or hemoglobin, or both. The greater the accuracy of medical diagnosis, the fewer will be the conditions to be labelled Anemia." As "inflammation," ''fever," "indigestion," have gradually marched out of the column of diseases into the field of symptoms, so must also anemia. And as chlorosis has lost many of its class to tuberculosis, and pernicious anemia to malignant disease and to the animal parasites, even more must secondary anemia divide itself up and become a symptom only, and that of the most varied disorders. But, for the present, there must continue, for descriptive purposes at least, the symptom group, which may be called anemia. This group-name will include visible pallor, alterations in the physical and chemical characters of the blood; circulatory dis- turbances, such as palpitation of the heart and dyspnea, and a tendency to edema; various muscular and nervous disturbances, or as has been stated, any alteration in the respiratory function of the blood. The particular phase of the symptom group which is most in evidence will vary with the cause of the anemia, and here one must be cautious in drawing conclusions, as in many instances, not the anemia itself, but the primary cause of the anemia, may be responsible for the symptoms. For example in the anemia of tuberculosis the pallor is a marked feature, while the diminished quantity of blood renders the blood count often but little removed from the normal. Again, in beriberi edema may be as prominent a feature as pallor, while in malignant disease the pallor as such gives way to the well- known cachectic hue. The blood characteristics of secondary anemia are a diminution of red cells and hemoglobin, but with low color index, but though this is typical, there are also secondary anemias such as that due to Ankylosto- mum and Bothriocephalus, where the blood picture runs closely parallel with the primary Addisonian, or pernicious form. The pathological anatomy of secondary anemia is, of course, the anatomy of the process which has given rise to the anemia, but there are certain con- ditions more or less directly referable to the anemia itself, such as pallor of the organs and fatty de- generation, particularly noticeable in the heart and in the liver, in the capillary blood-vessels; and changes in the bone-marrow, which may, however, vary according to the excitant of the anemia. Broadly speaking, the secondary anemias may be divided into the Acute and Chronic. Acute Anemia. — The one great cause of this condition is hemorrhage, either externally, or into one of the body cavities. This may be due to trauma or surgical operation; uterine hemorrhage occurring either during an abortion, or after delivery, 354 pulmonary or gastric or intestinal solutions of con- tinuity may give rise to external bleeding, while a rupture of the liver, spleen, or kidney may be a cause of internal bleeding. Symptoms. — Anemia from any of the above causes shows itself by certain well defined signs: (a) Pallor. (b) Actual shrinking of the body; this is brought about by the flow of the body fluids toward the blood- vessels to make up for blood lost. The shrinking shows itself in the drawn face, sunken eyes, s cadaveric expression. (c) Nervous Symptoms. These are dependent upon cerebral anemia, and manifest themselves through the reaction of the medullary centers; of these, the respiratory center gives the earliest and t In- most obvious warning, such as sighing, disturbed respiratory rhythm, rapid respiration, or in a later stage actual air hunger. (d) Psychical manifestations, as restlessness, mild forms of delirium, failure to appreciate one's surroundings. (f) Amblyopias which may terminate in optic atrophy are also to be found. (f) 'the Blood Picture. Crile's observations upon the donors in transfusions showed a fall in both hemoglobin and red cells, beginning immediately after the bleeding or up to several hours after. The white cells in nearly all cases showed a sudden sharp rise in number, and this rise was maintained above the previous level for four or five days. In a small series of experiments made to compare the blood pic- ture of hemorrhage and shock, Crile found that the diminution of red cells and hemoglobindid not occur in shock, and the rise of white cells was not observed. (g) Cardiovascular Symptoms. A rapid pulse, becoming more rapid with increasing hemorrhage, is an almost invariable sign in acute anemia. The blood pressure falls and the heart sounds become weak, due not only to the diminished total volume of blood, but to the diminished flow through the coro- nary vessels and consequent impairment of the heart muscle. The diagnosis between shock and acute anemia from hemorrhage is naturally difficult in the ab- sence of external bleeding, or of evidence of free blood in a body cavity, since most of the symptoms of the two are identical. However, a preliminary stage of restlessness, an increasing pulse rate and the early appearance of diminished hemoglobin and red cells with increase of leucocytes, speaks strongly for anemia from hemorrhage. Subacute Anemia. — As opposed to the sudden onset of the anemic syndrome, we have to deal with one having a rapid onset in which the condition may develop in days or hours instead of minutes. Such a condition has been reported in acute septicemias. Chronic Anemia. — Among the chronic anemias, though their cause is legion, the following groups may be cited: 1. Anemia from continued losses of blood, e.g. hemorrhoids. 2. Anemia from infectious diseases, e.g. tuberculo- sis, rheumatism, typhoid fever, syphilis, sepsis. 3. Anemia from parasites, malaria, uncinariasis, bothriocephaliasis. 4. Anemia from malignant disease. 5. Anemia from intoxications by lead, arsenic, cocaine, morphine, carbon monoxide, carbon dioxide, and in nephritis and pregnancy. 1. Continued Small Hemorrhages. — This cause may give rise to a most profound degree of anemia which may, in some instances, show a blood picture very similar to that of pernicious anemia. The common causes are uterine hemorrhage in fibroids and chronic metritis and carcinoma, hemorrhoids, purpura, and hemophilia. i;i i EREN< i: II WiU'.ooK OF THE Ml DICAL S< [] VncMii.i. Secondary These are cases which show an extreme degri f pallor, and also acquire t lie drawn, haggard look oi chronic ill health; as a rule there is also associated a iderable degree of loss <>f weight, but it is rare them to manifest any appearand lexia. Tlic patient may be quite unconscious of the cause of his steady decline in health, since many of the ca rhage are painless, ii is not uncommon for such a patient to be dosed over long periods with inm and tonics, while the actual can-.' is unsuspected. In this form ol anemia there is usually a considerable diminution, even to 1,500, r 2,000,000 ii number of red blood cells with a color index still more diminished, and as a nil'', a slight or moderate leuco- cytosis. An extreme grade of poikilocytosis may be present ami normoblasts may be found in i at sometimes. Megaloblasts may also be found, but iiim-h less commonly, and never in a majority of the nucleated red cells (( 'abot). cases may be difficult to distinguish by. the blood picture alone from primary anemia. 2, Infectious Diseases.— Tuberculosis, perhaps, of all diseases shows the greatest discrepancy be- tween the apparent anemia, as judged by pallor, and the diminution of the blood content as shown by examination. Red Cells. — In patients undergoing treatment counts of Li. 00(1.(1(10 or over are not uncommon, and the number rarely falls below 3,000,000. A slight diminution from the normal number is the usual condition found. After hemoptysis there isasudden slight reduction of hemoglobin. Commonly, even with marked pallor and loss of weight, the hemo- globin estimation gives a high figure, but the typical finding is one of less than normal and a color index which is reduced. It is claimed that in tuberculosis the red cells resist hemolysis to a greater extent than normal cells. The most satisfactory explanation of the relatively high red cell and hemoglobin estimation is that there is an actual diminution in the total blood mass, due to loss of body fluid by the skin, and through bronchial lion. In the treated cases also, hyperalimenta- tion, together with sun and fresh air, stimulate blood production. Leucocytes. — In many cases these are diminished and in non-progressive cases a count in the neighbor- hood of 5,000 is the rule. In cavity formation a cytosis is the rule and advancement of the disease is usually marked by an increase in the number of white cells, this increase being chiefly in the poly- morphonuclears. A lymphocytic increase has been shown to correspond with periods of improvement. Arneth has pointed out that the number of nuclei in a polymorphonuclear cell has a bearing upon prognosis. The greater the number of leucocytes with one or two nuclei, the graver the outlook, while an increase in cells having three to five nuclei is an indication of favorable import. Minor and Ringer confirm this work. The pallor of tuberculosis is notorious and, set off against the red lips and flushed cheeks, tells its own story; often, however, one sees the bluish-white, or skim-milk complexion, with a pale palate and con- junctiva?, while in the later cases a cachectic appearance not unlike malignant disease may make its appearance, especially in the poor and ill-cared for. Si pticemia. — Here is found a quality of anemia which in acuteness nearest approaches that due to hemorrhage. The red cells may diminish at the rate of 1,000,000 a week, and extremely low counts have been recorded. Hayem's case of puerperal sepsis showed only 1,450.(100 with twenty per cent, of hemoglobin. The hemolysis is so marked and so rapid in severe cases, that the hemoglobinemia causes staining of the organs, and to this is due the sallow icteroid tint of acute sepsis. Leucocytosis. — Polymorphonuclear leucocytosis is the rule, except in some fulmii es where there may be actual leucopenia. With leucocyti or in the al leucocytosis, the presence of red- !i granules in i he polj nucleai ile leuco- cytes when I real i 'd by iodine, either in vapor or solu- tion, is said to be distinctive of a septic or toxic Methe elobinemia has been recorded following sept icemia t rom Ba< llv The anemia of rheumatic fever lias many of the characters of that found in sepsis and shows itself early in the disease by a diminution of red cells, with a greater diminution of hemoglobin, but rarely to the same degree as in Sepsis. Li i- is usually present. :!. Parasites. — CJm which has of late yi been recognized as a cause of the endemic anemia in many districts, may give rise to an acute illness or may run over years. Besides the blood changes there are symptoms referred to the digestive tract. Abdominal pain relieved by f 1, perverted appetite, dyspepsia, constipation followed by irregular diar- rhea, and with blood frequently found in the mo- tions. Adults, the subjects of chronic infection, may show the vocal, bodily, and sexual characters of infantilism. The blood picture shows a red blood corpuscle count which may range from 800,000 to 1,200,000 with a low color index. The cells may be altered in size, shape, and coloring. Normoblasts are frequent and megaloblasts are often found but not as a majority of the nucleated cells. Eosinophilia is characteristic and is most marked before the anemia is pronounced. A rise in the eo- sinophilia is of favorable import. The number of these cells has been found as high as sixty-six per cent, with an average of eighteen per cent. The diagnosis is suggested from the symptoms in an infected locality, especially when there is a history of boils or a papular skin eruption. The finding of ova in the stools is diagnostic. Thymol in fifteen to thirty grain doses repeated for three or four times at short intervals (one to one and one-half hours) followed by a purge, is the treat nient of choice; but toxic symptoms from the drug such as vertigo, delirium and brown colored urine, must be kept in mind. After one week the stools should be examined and if ova are still found the treatment should be repeated. Malaria. — The chief characteristic is the rapidit}' of its onset; a drop of from five to ten per cent, in red cells may occur with each paroxysm. Grawitz records a fall of 400,000 in six days. The hemoglobin content falls in proportion. Manson sugge.-ts that the rapidity of the fall in the number of red cells is due to the liberation of lytic substances into the plasma which continue the corpuscular destruction. Mary Rowley Lawson suggests that the cause of the rapid blood destruction is the migration of parasites from corpuscle to corpuscle, destroying one after the other. The blood volume in malaria is also diminished. After recovery from the infection in the tertian and quartan forms, the blood recovery is fairly rapid, but in estivoautumnal fevers the anemia is liable to continue. In some pernicious forms the blood destruction may be extraordinarily severe, the red count falling as low as 500,000, with the absence of any nucleated red cells, indicating an absence of marrow reaction. In other cases a blood picture closely resembling that of primary anemia may be seen. .Malarial cachexia follows usually a chronic estivo- autumnal infection. Here the red cells may drop to less than half the normal, while the hemoglobin shows a corresponding diminution. The mononuclear leucocytes are increased in number, while pallor with sallowness, dyspnea, edema, and weakness are usually prominent. A much enlarged spleen is 355 Anemia, Secondary REFERENCE HANDBOOK OF THE MEDICAL SCIENCES characteristic of the condition. Plasmodia may be with difficulty discovered in the blood. 4. Malignant disease is cue of the most constant causes of severe grades of secondary anemia. It is rare to find a malignant growth at all advanced which has not given rise to some blood deterioration. The typical finding is a greater or lesser decrease in the number of red cells, with a greater diminution of hemoglobin, and a moderate degree of leucocytosis. In cancer of the stomach of typical form, the average red blood corpuscle count will be about three to four millions, though in rare instances the count has gone above five millions, and less rarely as low as one and a half million. Poikilocytosis and polychromato- philia are not uncommon. Basophilic granules and iodophilia have also been noted. Jez reports the finding of nucleated red cells — normoblasts — with frequency, and even in cases where the red count was 4,000,000. The hemoglobin value is practically always dimin- ished, and in 150 cases collected by Osier and McCrae averaged fifty per cent. The hemoglobin content falls before the red cells and the color index ranges usually between 0.4 and O.S. The white cells are nearly always at or above the normal, rarely below; a white cell count of 10,000 will be an average for any large number of cases. A differential count shows a polynuclear estimation of seventy-five per cent. A digestive leucocytosis is a^ a rule absent. The resistance of the red cells is increased. Besides these typical cases of gastric cancer, Marcorelles points out a group of cases in which the anemia is the outstanding feature. Here we find, (a) Clinical signs of cancer of the stomach, with intense anemia {forme avec anemie). (b) Very intense anemia without obvious signs of cancer (forme animique). (c) The form with metastases in the bone marrow. The appearance of the first two groups is one of excessive pallor without the characteristic yellowish tint of the ordinary case of cancer. The patient appears exsanguinated, and though usually ema- ciated, sometimes shows retention of adipose; edema is common and asthenia is profound, palpitation and ringing in the ears are frequent. The digestive disturbances are those found in other grave anemias. The red cells range from three-quarters of a million to three millions. The hemoglobin index, though usually below 0.5, may rise to 1 or over. Poikilocyto- sis is the rule and nucleated red cells are numerous. The leucocytes usually range above the normal and the formula is various, a polymorphonuclear increase being the rule, but a mononuclear increase is not uncommon. Eosinophils are increased and myelo- cytes are sometimes found in considerable numbers. It will be seen that in almost every particular the blood picture here may simulate that in primary pernicious anemia. Cases with Involvement of Bone Marrow. — Clin- ically, these are accompanied by tenderness over the bones, by splenic enlargement and by hemorrhage in retina, gums, and skin. The blood picture differs from that of the previous form in the more frequent elevation of the hemoglobin index and in the greater number of nucleated cells, particularly megaloblasts. 5. Chemical Poisons. — The type of this group is saturnism, which gives rise to most intense forms of blood deterioration. The pallor is usually marked and is frequently the most noticeable feature. It is quite frequently associated with a tinge of sallowness. The blood picture shows a lessened number, often a; low as 3,000,000, of red cells, a hemoglobin percentage relatively lower, and a leucocyte count not differing much from the normal in number or in variety. Two features of the red cells are almost constant, basophilic granulation and polychromatophilia. Baso- philia is more common than in any other disease in a case where the anemia is not extreme. A lead line will usually give the clue to the cause of the anemia if looked for, but many cases occur where the infection is accidental rather than industrial, and for this reason the cause of the anemia may remain unsuspected. The anemia of nephritis may, in the present state of knowledge, be also classed among the toxic anemias, admitting, however, that it would probably be more correct to attribute the anemia and the nephritis to a common cause, rather than the anemia to the nephritis. Though practically all forms of nephritis show a certain grade of anemia, it is most marked in that group classed as " chronic parenchymatous," where pallor and edema are the classical symptoms — "large white legs, large white kidneys." The blood picture is a diminished red count and a greater diminution of hemoglobin with often a lowered specific gravity due to the hydremia. The freezing point, though usually low, may rise to normal from the same cause. The anemias of infancy are even yet an ill- assorted lot, the condition known as von Jaksch's disease being the central figure. The clinical features of anemia, splenic enlargement, glandular enlarge- ment, and enlargement of the liver, may exist with marked diversity of the blood picture, and, on the other hand, there are seen in rickets, syphilis, and tuberculosis, cases with similar clinical characters. The blood picture in infancy is extremely unstable, variations in the characters and proportions of the cellular elements occurring with the greatest readiness. For this reason, in infancy any diagnosis founded upon the blood examination alone is open to almost certain error. Setting aside forms of anemia common to adults, there remain the anemias due to malnutrition, faulty feeding, bad hygiene, enteric diseases, marasmus, etc. The Anemias of Old Age. — "A moist eye, a dry hand, a yellow cheek, a white beard," are commonly the things which "accompany old age," and many troubles incidental to senility are also causes of anemia. Hypertrophy of the prostate, with its accompanying cystitis in men and a senile endometri- tis in women; arteriosclerosis and contracted kidney; infections of the mouth, as pyorrhea; neoplasms in various situations; and by no means least, the senile forms of tuberculosis, may all be reasons for the anemia of the aged. AYhether infections of the intestinal tract shall be proved to be as Metchnikoff considers them, the foundation of old age, as well as of some of its anemias, remains to be seen. Diagnosis. — In acute anemias, the distinction be- tween shock and hemorrhage has been already mentioned. It is of service to remember that in rare instances an acute anemia may occur from the action of an actively hemolytic agent as in some acute infections, and in poisoning by ricin, potassium chlorate, or nitrobenzol. Chronic Anemias. — The diagnosis here is from chlorosis and from primary pernicious anemia. This must be made by exclusion on the one hand, and recognition on the other. In young women tubercu- losis, Graves' disease, nephritis, lead poisoning, and gastric ulcer must be eliminated before chlorosis is diagnosed. A conscientious use of the thermometer, and if necessary, of tuberculin, will often clear up doubt in the case of tuberculosis, and in the other cases the recollection of the causes suggests the avenue by which the distinction may be made. Pernicious anemia, as a rule, offers a definite blood picture, but it must be remembered that there is no single pathognomonic sign. Under forty, a diagnosis of pernicious anemia should be viewed with suspicion. At the age when this disease is in question, ma- 356 RKFKUKNCE HANDBOOK OF THE MEDICAL SCIENCES AnestheBla and Analgesia lignancy insome portion of the digestive tract must be always before the mind. Repeated hemorrhages, unknown to the patient, and animal parasites arc other causes of anemia in which pernicious anemia may be simulated. The examination of the rectum and of the stools may give the clue to the cause. To summarize— the diagnosis of the cause ol a ndary anemia i- made with certainty only after mtine examination of the whole body, and only when no cause for blood deterioration can be made out is a primary anemia to I"' considered. If then a sponding blood picture be found, that opinion infirmed. Aplastic anemia is a disease of young person-. chiefly women. The color index is low and lympho- cytes form the great proportion of the white cells. Milar leucocytes are few and nucleated red cells practically absent. The disease runs a progres- sively downward course. After the elimination of the so-called primary anemia-, the further apportioning of the direct cause of the anemia is done by the associated symptoms. Treatment. — In the face of so varied an etiology, it would appear useless to suggest any one form of treatment. The diagnosis is everything. This may indicate a transfusion for acute hemorrhage, an excision of hemorrhoids for recurring hemorrhage, a change of diet for scurvy, an antituberculous regime, or antisyphilitic medication; a change of occupation for plumbism, or a change of climate for nephritis; a laparotomy for cancer, or an anthelmintic for parasites. In addition to these obvious procedures, the direct i upon blood production of sunlight and in- creased elevations should not be overlooked. The diminished respiratory function of the blood in anemia calls for free flowing fresh air, and the per- verted metabolism for extra assimilable nutrition. Of drugs, we may say there are but two — iron, which has not the specific action it shows in chlorosis, but which i- generally useful, and arsenic which clinically, at any rale, does improve the blood production. Were the writer to be limited to three preparations of iron, these would be Blaud's pill, the tincture of chloride of iron in an acid mixture as dilute phos- phoric acid, and syrup of the iodide of iron. Ma-sage and certain hydrotherapeutic douches may be of definite value; and last, but not least, rest in bed, which, after the correction of the primary cause, may alone work wonders. A. H. Gordon. Anemia, Splenic. — See Splenic Anemia. Anencephalus. — See Teratclogy. Anesthesia and Analgesia. — Definition of Terms. — Anesthesia, accurately speaking, denotes the loss of e of touch. The term is often used to indicate the loss of all forms of sensibility, as pain, tempera- ture, muscular location, etc. In this article, when the word is used without qualification, it shall mean the loss of tactile sense. Tactile sensibility is sub- served by structures that take cognizance of change of contact, and are stimulated by motion of an ex- ternal object in contact with the surface. Analgesia is a term employed to denote the loss of sensibility to painful impressions. Thermoanesthesia is a loss of temperature sense. Present day clinical neurology has been compelled in large part to abandon these general terms since the more extended observations of Head and those fol- lowing him have shown that the sensations, hereto- fore thought of as simple, are in reality very complex, and that it is far better to express one's clinical findings in terms of the test used, than by the em- ployment of general terms. Thus one discriminates between touch sensibility to cotton wool, and pri - sure sensibility to the finger touch. Lo ia) ol one does not imply loss of the other. A patient may lose the ability to distinguish between extremes of neat and cold and yet retain the ability to dis- criminate between very minute variations in warmth or coolness. Mi iioiii- 01 Testing Sensibility. — The determi- nation of the varying degrees of anesthesia and anal- gesia is made difficult by the fact that the physii must depend upon the statement of the patient for his information. The intelligence, attention, and sincere cooperation of the patient are necessary to secure reliable responses. Furthermore, individuals vary, within the limits of what is normal, quite appreciably in their sensibility to external irritation. finally, in patients suffering from lesions which cause either a slighter, or perhaps a greater degree <>f hiss of consciousness, sensibility is more or less diminished up lo entire loss of sensation, even though the lesion may cause no anesthesia directly. In testing sensibility, the patient should be blind- folded or in some other way prevented from seeing what is being done, in order that simulation or self- deception may be avoided. It is remarkable how vividly one can feel the prick of a pin or touch of a feather through the medium of sight. When the lesion is unilateral, a comparison of the two sides is very desirable. Various instruments of precision have been devised by neurologists for testing sensi- bility (see Esthesiometer). Some are indispen- sable, others of value only in carrying out systematic and controlled observations. A systematic sensory examination is recognized to be of extreme impor- tance, and of recent years has become successively more extended and precise. The following scheme or schedule laid down by Head and Holmes con- tains the usual present day necessities for a complete sensory examination. A. Spontaneous Sensations: Pain, numbness, tingling, position of the limb, idea of the limb, hallu- cinations or illusions. B. Loss of Sensation: 1. Touch: a. Light touch, cotton wool on hairless and hair clad parts; threshold with von Trey's hairs. b. Pressure touch, threshold with pressure es- thesiometer. 2. Localization: Naming the part touched; Henri's or Head's method, target, etc. 3. Roughness, threshold with Graham-Brown's esthesiometer: Sandpaper tests, discrimination of relative roughness. 4. Tickling and scraping: Tickling on soles and palms; Cotton wool rubbed over hair-clad parts; Light scraping with finger nails. 5. Vibration, tuning fork: Loss or diminution of sensibility, Alteration in the character of the sensation evoked. 6. Compass points: Points simultaneously applied. Points successively employed. 7. Pain: a. Superficial pain: pinprick; threshold with algesimeter; reaction to measured pain- ful stimuli. b. Pressure pain: threshold with the algo- meter; reaction to painful pressure. 8. Temperature: Thresholds for heat and cold: Effect of adaptation on threshold; 357 Anesthesia and Analgesia REFERF.XCF, HANDBOOK OF THE MEDICAL SCIENCES Discrimination of different degress of heat and cold; Affective reactions (a) to extreme degrees, (6) to warmth. 9. Position: By imitating with the sound limb the position of the affected limb; By pointing with the sound limb: Measurement of defect by Horsley's method. 10. Passive Movement: Appreciation of movement; Recognition of the directions of movement: Measurement of the angle of the smallest movement which can be appreciated; Falling away of the unsupported limb when the eyes are closed. 11. Active Movement: Imitation of movement by the sound limb; Ability to touch a known spot; Measurement of the defect by Horsley's method. 12. Weight: a. With hand supported, Recognition of differences in weights applied successively to one hand; Appreciation of increase or decrease of weight; Comparison of two weights placed one in each hand. 6. With hand unsupported, Comparison of two weights placed one in each hand; Recognition of differences in weights applied successively to one hand. 13. Size: I Hfference— threshold. Distinction of the head from the point of the pin. 14. Shape (two dimensional). 15. Form (three dimensional): Recognition of common objects by their form. 16. Textures: 17. Dominoes: Ability to count points by touch. 18. Consistence: 19. Testicular sensibility: o. Light pressure; 6. Painful pressure. 20. Sensibility of glans penis to measured prick. Such a detailed examination is demanded by the present day knowledge of the sensory nervous sys- tem. This knowledge is the accumulation from a number of research workers. The most important researches have come notably from English physiolo- gists and clinicians. A brief summary of this work as outlined by Head and Holmes in a recent (1912) monographic presentation will be found useful. They write that it is a matter of universal belief that man has evolved from the lower animals, and yet when we deal with sensation and sensory processes, we speak as if he were created with peripheral end organs capable of reacting to one of the sensory qualities of human experience. The impulses start- ins: in these end-organs are supposed to pass unal- tered to the brain, there to set up that peculiar and unknown change which underlies a specific sensation. Spots were found on the skin sensitive to touch, to pain, to heat, or to cold only. With the discovery of these highly developed end organs, the doctrine of specific nerve energy seemed to be proved in the strictest manner. All other forms of sensory appre- ciation were supposed to be produced by the psychical transformation of these primitive sensory elements, in association with an ill-defined faculty called the "muscle .sense." Recognition of the locality of a stimulus, and the posture of the limbs were attrib- ute 1 to judgment and association. But alongside the systematic investigation of von 358 1 rev, and others, of the capabilities of these specific areas in the skin the clinicians were discovering the importance of "muscular sensibility." Sherrington's demonstration of afferent fibers in muscles and ten- dons placed the existence of the "muscle sense'' beyond a doubt, and the use he made of these afferent impulses from deep structures, in his theory of the proprioceptive system, necessitated a complete explo- ration of the nature of deep sensibility. ■■ By their experiment directed to this end, Rivers and Head showed that beneath the skin, indi of all "touch" and "pain spots," lies an afferent system capable of a wide range of functions. Pres- sure, that in ordinary life would be called a touch, can be appreciated and localized with considerable accuracy. Increase of pressure, especially on bones and tendons, will cause pain. Moreover, it is from the impulses of this deep afferent system that we gain our knowledge of the posture of the limbs and the power of recognizing passive movements. Evidently, therefore, the peripheral mechanism of sensation is less simple than was at first supposed. For there are two sets of end organs, that can respond to tactile stimuli, and two independent mechanisms for the initiation of pain. Further analysis showed that the peripheral apparatus in the skin, by which we become conscious of the nature of external stimuli, is highly complex. No one sensory quality is sub- served by a single set of end organs, but every specific sensation is the result of the combined activity of more than one group. This is exactly the result that might have been expected, when we bear in mind that the structure of man is the product of a long evolution. But it is equally obvious, from an evolutionary standpoint, that these diverse impulses could not pass uncombined to the highest physiological level. Within the spinal cord, the opportunist grouping of the periphery gives place to an arrangement according to quality (Head and Thompson). All impulses capable of generating pain become grouped together in the same path, and can be disturbed simultaneously by an appropriate lesion of the spinal cord. The most remarkable condition revealed by an intramedullary lesion is the complete separation of the impulses underlying the appreciation of posture, the discrimination of two points, and their corre- lated faculties from those of other sensory groups. All painful and thermal impulses coming from the periphery undergo regrouping after entering the spinal cord, and, whether they arise in the skin or in deeper structures, become arranged according to functional similarity. Then, after a longer or shorter course, they pass away to the opposite side of the spinal cord. This process of filtration leaves all the impulses associated with postural and spacial recognition to continue their course unaltered in the posterior columns; they are the survivors of peripheral groups broken up by the passing away of certain compo- nents into secondary afferent systems. At any point in the spinal cord these columns transmit not only impulses from the periphery which are on their way, after a shorter or longer passage, to regrouping and transformation, but at the same time they form the path for impulses, arising both in the cutaneous and deep afferent systems, which undergo no regrouping until they reach tlie nuclei of the medulla oblongata. Thus, a lesion confined to one-half of the spinal cord, even at its highest segment, may interfere with the passage of sensory impulses, some of which are traveling in secondary paths, while others are still within the primary level of the nervous system. All impulses concerned with painful and thermal sensa- tions from distant parts, disturbed by such a lesion, will be traveling in secondary paths and will have come from the opposite half of the body: for. after regrouping, they have passed across the spinal cord. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia and Analgesia But those impulses underlying the appreciation of posture, the compass test, size, shape, form, weight, consistence, vibration, will be affected on the same half cf the body as the Lesion. They still remain in paths of the peripheral level and have undergone n.i regrouping. In such a case the parts on the side opposed to the lesion may l"' insensitive to pain, heal and cold; but all the postural and spacial aspects of sensation will ba perfectly maintained. Yet, all power of recog owing position, of estimating size, shape, form and weight, or of discriminating the two compass points, will lie lost in the limbs which lie on the side of the in, although tactile sensibility and localization the spot stimulated maj be perfectly preserved. This remarkable arrangement enables one to analyze the nature of the peripheral impulses upon which depend our power of postural and spacial recognition. Obviously, even at the periphery, they must be independent of touch and pressure. The r to distinguish two points applied simultane- ously and to recognize such size and shape, requires as a preliminary the existence of sensations of touch; the patient may be deprived of all such powers of spacial recognition without any discoverable loss of tactile sensibility. In the same way, our power to appreciate the position of a limb, or to estimate the weight of an object, is based upon impulses which, even at the periphery, exist apart from those of touch and pressure called into simultaneous being by the same external stimulus. This long delay of the postural and spacial ele- ments in reaching secondary paths enables them to give off afferent impulses into the spinal and cere- bellar coordinating mechanisms, which lie in the same half of the spinal cord. The impulses which pass away in this direction are never destined to r consciousness directly. They influence co- ordination, unconscious posture and muscular tone, and, although arising from the same afferent end organs, they never become the basis of a sensation. finally, the last survivors of these impulses from the periphery become regrouped in the nuclei of the posterior columns and cross to the opposite half of the medulla oblongata in paths of the secondary level. So they pass to the optic thalamus and thence to the cortex, to underlie those sensations upon which are based the recognition of posture and spacial discrimination. Groups op Sensory Disturbances. — In clinical neurology and psychiatry it is important to realize then that it is possible closely to localize and delimit sensory disturbances into the following groups: 1. Sensory disturbances of the peripheral neurons: Neuralgia, neuritis, etc. 2. Sensory disturbances within the cord. 3. Sensory disturbances of the brain stem. I. Sensory disturbances of the optic thalamus. 5. Sensory disturbances of the cortex: (a) Due to altered fiber tracts (so-called organic); (6) Due to altered ideation (psychical alterations as seen in psychoneuroses and psychoses). 1. Sensory Disturbance in the Peripheral Neurones. — No attempt will be made here to give the specific anatomical disturbances such as underlie the various neuralgias and neuritides. The laying down of general principles which enable one to determine that the lesion is one of the peripheral neurone is alone attempted. Thus the various sensory dis- turbances occurring in diseases of the cranial nerves, the branches of the cervical, or brachial plexus, the thoracic nerves or the lumbar and sacral plexuses, will be found under their appropriate headings: trigeminal neuritis, brachial neuritis, median nerve, intercostal neuralgia, sciatica, etc., etc. Attention will be directed here solely to certain general facts which the work of Head, Rivers and Sherren have bought out relative to the peripheral sensory system. They first show thai the ordinary method of testing for sensibility, i.e. by touching with the linger is worthless. It fails to show, in per- ipheral lesions, such as sections of the median oi ol the ulnar nerve, that grave def cl oi en ibility may i" present, for the pressure touch of the fingers is after all a type of test for deep sensibility, and that i he tibers for deep sensibility pass nil in t he tendons, muscles or deep motor nerves. Thus in a wound, say of the wrist, severing median or ulnar or both, pre ure touch would not be involved at all, unless the tendons were also divided, but that tests by cotton wool and by pin prick would show marked epicritic and protopathic loss respectively are ac- curately locahzable. Their researches sh.ev that. e types of sensibility, subserved by distinct se ts of libers, must be distinguished in the eutan. system. These are the protopathic, the epicritic and deep sensibility fibers. Protopathic sensibility is the more elementary and original type of sensibility, It, is that which serves as a general protection of the animal body from harm. It distinguishes pain, as from pin prick, it distinguishes between extreme ot heat and cold, but not between warm and cool. Epicritic sensibility on the other hand is a specialized discriminative type of sensibility. It distinguishes light touch as by cotton wool, determines minute variations in temperature, localizes compass points which are close together. Deep sensibility finally is concerned with postural sense, and deep pressure sense tested by an algesimeter (Carttell) the epi- critic and protopathic sensibilities travel in the cutaneous system, that of deep sensibility in the ten- dons and muscles and motor nerves. Attention has been called to the fact that in severe nerve injuries deep sensibility is lost only when tendon or muscle or motor nerve is implicated. Again, as in median or ulnar nerve injury it is observed that if the periphery is involved the area of insensibility to cotton wool is usually larger than that of pin prick. Immediately following the injury they may be coterminous but soon the condition of wider extension of epicritic touch loss becomes apparent. When the lesions reach the main branches of the plexuses however it is noted that the epicritic and protopathic loss is about equal and enduringly so until recovery takes place, whereas, and this is an interesting point brought out by Head, when the injury involves the sensory roots, there is a peculiar reversal of the reaction and here the loss to pin prick is wider and more extensive than the loss to cotton wool. In recovery the practical point to bear in mind is that if the area to cotton wool loss rapidly recedes, i.e. within five or six weeks, it is probable that the nerve affected has been partially cut across only. Cotton wool loss usually persists about 100 days in a totally divided nerve before recovery commences to set in. If after that time the area to cotton wool loss does not recede, operation is indicated. Testing then by cotton wool, by pin prick and for deep sensibility are absolute necessities in determining lesions of the per- ipheral nervous system. For research purposes the use of compasses, of von Frey's hairs, of measured thermal and pressure stimuli, are necessary. In practical work they are valuable but under certain circumstances may be dispensed with. 2. Disturbances of Sensibility in Spinal Cord Affec- tions. — Similarly no detailed description of the diseases of the spinal cord will be attempted. It is well-known that one disease process will give rise to a number of clinical pictures. Thus a plaque of mul- tiple sclerosis may give rise to the picture of a tales, amyotrophic lateral sclerosis, a poliomyelitis, a spastic paraplegia, or a complete transverse myelitis. This section will deal only with those diagnostic criteria which from the analysis of the sensory symp- toms alone indicate that the sensory paths are inter- rupted in their spinal course. 359 Anesthesia and Analgesia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES In the previous section it has been shown that the epicritic, protopathic and deep sensibility fibers are capable of being stimulated separably and that these three systems remain distinctly isolated as systems. Not so in the spinal cord. Here an entirely new dis- tribution takes place and we find that functional pathways make way for quality paths: Heat as heat, cold as cold, pain, pass up separately, and there is no longer any distinction between epicritic and pro- topathic heat, epicritic or protopathic pressure, etc . such as is found in the cutaneous system in the arms or legs. In the spinal cord one finds the pain and thermal fibers usually crossing the cord — traveling up in the spino-thelamic paths in the anterolateral portion of the cord. Deep sensibility fibers, subserving postural sense, pass up in the posterior columns of the same side, while pressure touch usually passes up both sides of the cord. The work of Head and Thompson has given the main clue to the study of the different forms of sensibility in their pathological alterations in lesions of the spinal cord. 3. Disturbances of Sensibility in Lesio?is of the Brain Stem. — Disease of the brain stem offers special problems of diagnosis of extreme difficulty, so far as the analysis of the sensory disturbances is concerned. So long as the sensory paths were in their spinal route they were capable of a certain amount of isola- tion either as they entered the cord and made their first synapses, or as they continued up the cord in primary or secondary paths. But as these paths converge to enter the brain stem they become closer anatomically, disease processes are apt to overrun many paths, and thus the analysis becomes increas- ingly difficult up to the entering of these paths into the optic thalamus. Head and Holmes hold that the impulses under- lying sensations of pain, heat, and cold seem alone to run unaltered, either directly or by intercalated fibers associated with the ganglion cells of the forma- tio reticularis, between the upper end of the spinal cord and the optic thalamus. Here are received the regrouped secondary impulses from the face which cross and join the specific paths for pain, for heat or for cold. These paths are so situated that they can be interrupted without disturbance of any other form of sensation on the body, and the anal- gesia and thermoanesthesia so produced resemble in quality the loss of sensation to pain, heat and cold caused by a lesion in the spinal cord. Thus when a lesion of the bulb interferes with sensation of pain, not only may the skin be insensitive to prick, but the readings of the pressure algometer may be raised on the analgesic side. In the same way the affected area of the body may be insensitive to all degrees of heat, and to all stimuli capable of evoking normally a sensation of cold. Here, how- ever, in the bulb, in distinction to lesions of the cord, the grosser form of pain and discomfort may traverse other paths if the usual ones are closed — whereas in the cord all painful impulses are blocked by an equivocal lesion. In the bulb moreover all three forms of sensibility may be affected together or any one may escape or be alone involved. These impulses of pain, heat and cold all run up in the neighborhood of the fifth nerve nucleus, and in cases of occlusion of the posterior cerebellar artery the paths are usually implicated. This same accident may occasion a dissociation of the impulses underlying the appreciation of posture and passive movement from those concerned with spatial discrimination. A summary of the findings which may occur in the lesions which cut off the sensory pathways between the nuclei of the posterior columns and the optic thalamus has been stated by Head and Holmes as follows: 1. The impulses for pain, heat and cold continue 360 to run up in separate secondary paths on the opposite side of the nervous system to that by which they entered. They receive accessions from the regrouped afferent impulses from the nerves of the head and upper part of the neck. Although these paths are frequently affected together, they are independent of one another, and any of the three qualities of sensation may be disso- ciated from the others by disease. 2. Lesions of the spinal cord tend to diminish simultaneously all forms of painful sensibility, but with disease of the brain stem the gross forms of pain and discomfort may pass to consciousness, although the skin is analgesic. This applies not only to painful pressure but to the discomfort produced by excessive heat. 3. The impulses concerned with postural recogni- tion part company with those for spacial discrimina- tion at the posterior column nuclei. Up to this point, they have traveled together in the same column of the spinal cord, but as soon as they reach their first synaptic junction they separate. Above the point where they enter secondary paths, the power of recognizing posture and passive movements can be affected independently of the discrimination of two points and the appreciation of size, shape and form in three dimensions. 4. It would seem as if those elements which under- lie the power of localizing the spot touched or pricked become separated off from their associated tactile impulses before they have actually come to an end in the optic thalamus. The long connection of local- ization with the integrity of tactile sensibility is here broken for the first time. All these changes are preparatory to the great regrouping which takes place in the optic thalamus. 4. The Thalamic Syndrome and Se?isory Changes in Disorders of the Thalamus. — Practically the entire mass of sensory fibers carrying impulses of all kinds — the tests for most of which have already been outlined — have synaptic junctions within the optic thalamus. No note has been made here of the numerous fibers coming from the chemical receptors of the respiratory, gastrointestinal, or genitourinary tract, nor those from the organs of internal secretion, nor even of the sympathetic — all of these make up an enormous terra incognita for the future explorer. Lesions in and about the thalamus cause sensory symptoms, as well as motor ones, of a very char- acteristic nature — so much so that one can speak of a special thalamic syndrome. Such a syndrome was first described by Dejerine and his pupils, particu- larly by Roussy, who devoted a monograph to the subject. Here one observes the following notable features: 1. A persistent loss of superficial sensation of one- half of the body and face. This loss to touch, pain, and to temperature, is more or less definite, subject to considerable variation and to partial recovery, but the loss of deep sensibility, deep pressure, pos- tural sense, etc., is much more pronounced, and is more apt to persist. This latter is usually more marked distally and in many instances diminishes as one approaches the trunk. 2. There is slight hemiataxia and more or less com- plete astereognosis. 3. There are in the complete syndrome acute pains on the affected side which are very persistent, coming on in paroxysms. They are frequently extremely severe and rarely respond to the ordinary analgesics. These pains may involve a single member, may he limited to the side of the face, simulating a trigeminal neuralgia, or they may involve one whole side of the body. 4. There is usually a more or less distinct though slight hemiplegia, which in the unmixed syndromes rapidly clears up. Contractures rarely develop in the pure syndrome. In the mixed syndrome — with REFERENCE HANDBOOK OF THE MEDICAL SCIEN( I - Anesthesia and Analgesia extension of the lesion to the external capsule — con- tracl ures may be pres ;n1 . 5, Choreic, athetoid, or paralysis agitans-like movements may be present on the affected side. rhese are the symptoms which permit one to diag- nose a lesion of the optic thalamus and its surrounding pruts, but in addition to these Head ami Holmes have pointed out an extremely suggestive series of affect- ive reactions which arc due to lesions in the optic thalamus. They have opened up an attack upon the analysis of the sensory content of emotional reactions. They show that in thalamic lesions there ia a tendency to react excessively to unpleasant luli. The prick of a pin, painful pressure, exces- sive heat or cold, all produce more distress than on the normal half of the body. Thus, in one of Head and Holmes' patients, if a, pin is dragged lightly - the face or trunk from the sound to the affected side, there is felt an excessive discomfort passes the middle line. She not only complained that it hurt her, but the face was contorted with pain, and all this notwithstanding the fact that she was less able to distinguish head from point, yet the prick hurt her more. This very anomalous state of affairs is a purely thalamic reaction. This excessive reactivity is seen not only to pin prick, hut also to deep pressure, to extremes of heat and cold, to visceral stimulation, to scraping, rough- ness, vibration, tickling, to pleasureable stimuli, and to ideational emotional states. Not all patients show all of these reactions, but in practically ninety per cent, of the thalamic cases examined by Head and Holmes excessive affective response to one or more measured stimuli were found. For head and cold, and other forms of sensibility as well as for pain the exces- response may be present, and yet the patients are unable to detect — i.e. are anesthetic to — trie stimulus itself. So far as the ideational affective reaction is concerned these patients express themselves as follows: On hearing affecting music "a horrid feel- ing came on in the affected side, and the leg screwed up and started to shake." The singing of a comic song left one patient absolutely cold, but a tragic 2, produced a very distinct unpleasant effect. One patient said "my right hand seems to crave sympathy, my right side seems more artistic." In practically all of the cases the increased affective reaction was accompanied by actual sensory loss. \ more detailed study- of the loss of sensibility in thalamic disorders made by Head and Holmes re- vealed the following: Xo sensory^ functions are so frequently affected as the appreciation of posture and the recognition of passive movement. The amount of this loss varies greatly from a scarcely mensurable defect to complete want of recognition of the posture of the limbs of the abnormal naif of tic body. Tactile sensibility is frequently diminished; but, excepting in a few cases where all appreciation of contact was destroyed, a threshold could be obtained. It was always possible to show that increasing the Strength of the stimulus improved the proportion of right answers unless the observations were confused by the disagreeable tingling or other accessory sensations. Localization of the spot touched was defective in half the cases where sensation was sufficiently pre- served to carry out accurate tests. This inability to recognize the site of simulation was equally great, whether the patient was pricked or touched. In cases where localization was gravely affected, the disagreeable sensation, so easily evoked, tended to spread widely on the abnormal half of the body. A prick on the hand may cause an extremely painful ation in the cheek or side, and sometimes the patient simplv recognized the stimulus as a change within himself, and did not refer the discomfort from which he suffered to the action of any external agent. Sensibility to heat and cold may show all degl of change from total loss to a slight increase of the neutral zone. Beat and cold are not dissociated; and if one form of sensation is lost, the other will be ely disturbed. The apparent exceptio from a misinterpretation of the sensatio ed by high or low temperatures on the affected half of the body. \oi infrequent l\ I lie compa tesl cannot be carried out because of the gro sation and inability to recognize contact; but whenever this method can be applied a threshold can be worked out, and wii ing the distance between the points increases the accuracy of the answers. The power of estimating the relation between two weights is frequently disturbed on the abnormal half of the body. If the appreciation of posture and movement is affected, the patient can no longer recognize the identity or the differi vo weights placed in the unsupported hands. Hut so long as tactile sensibility is not diminished, he can still estimate the relation between weights applied one after tl ther to the same spot, and can recognize the increase or diminution in weight of in object already resting on tin- hand. The appreciation of relative size is often disturbed in tin but with care it is usually easy to dem- onstrate a difference-threshold. Shape and form in three dimensions are frequently not recognizable on the affected hand. But. if tactile sensibility is not grossly affected, the patient usually retains an idea that the object possesses a form, and may obtain a considerable percentage of right answers. Vibration of the tuning fork is recognized by all but three of our patients. In almost every case, however, the length of time during which it was appreciated was shorter, and sometimes the rate of vibration was thought to be slower on the affected half of the body. Roughness, as tested with Graham Brown's esthe- siometer. was always recognized, except in three cases where the loss of all forms of sensation was unusually severe. Usually the threshold was the same on the two sides, but it was occasionally raised on the affected hand, 5. Sensory Disturbances due to Cerebral Lesions. — The sensory paths from the thalamus to the cortex undergo a new distribution, thus making at least five distinct regroupings of the sensory phenomena in the entire course of the sensory neuron. The analysis of the phenomenon introduces more com- plex factors, and the necessity for abandoning all generalizations, even those more refined, that anesthesia, analgesia, as, for instance, light touch, cutaneous sensations, etc., become more apparent. Newer valid terms may be coined, but one is here forced to state the results in terms of the tests emploved. 1. Using graduated tactile stimuli such as von Frey's hairs, and the pressure esthesiometer, Head and Holmes have found as follows: A cortical lesion may reduce the accuracy of response from the affected part to graduated tactile stimuli. The form assumed by this defective sensibility differs from that produced by lesions at other levels of the nervous system. Here the affected part may respond to the same graduated hair as the normal hand; but this response is irregular and uncertain. Increasing the stimulus may lead to no corresponding improvement, and even the strongest tactile hair may occasionally evoke less certain answers than a hair of much smaller bending strain. Moreover, a touch with the unweighted esthesiometer may be as effec- tive at one moment as the same instrument weighted with 30 grm. at another. In such cases no tactile threshold can be any longer obtained. 2. This irregularity of response is associated with 361 Anesthesia and Analgesia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES persistence of the tactile sensation and a tendency to hallucinations of touch. Where the sensory defect is not sufficiently gross to abolish the threshold, persistence, irregularity of response and a tendency to hallucinate may still disturb the records. 3. In all cases where tactile sensibility is affected, whether a threshold can be obtained or not, fatigue is induced with unusual facility. Although the patient may cease to respond to tactile stimuli over the affeeted part in consequence of fatigue, his an- swers may remain as good as before from the normal parts. The fatigue is local and not general. 4. With stationery cortical lesions, uncomplicated by states of shock or by "diaschisis," sensibility to touches with cotton wool is never lost over hair-clad parts. Over hairless parts, stimulation with cotton wool may produce a sensation which seems "less plain" to the patient, and his answers may show the same inconstancy so evident when he is tested with graduated tactile stimuli. For measured painful stimuli they found that a pure cortical lesion leads to no change in the threshold to measureable painful or uncomfortable stimuli. Nor does the patient express greater dislike to these stimuli on one side than on the other. A prick may be said to be "plainer" or "sharper" on the normal than on the affected side; but this is due to a defective appreciation of the pointed nature of the stimulus and bears no direct relation to the pain- fulness of the sensation evoked. The temperature tests they found as follows: 1. The neutral zone, within which the stimulus was said to be neither hot nor cold, was considerably en- larged in comparison with that observed on similar normal parts of the same patient. 2. The patient complained that although he recognized correctly the nature of the stimulus, it seemed "less plain" than over normal parts. His answers were less constant and less certain; a tem- perature recognized without difficulty at one time seemed doubtful at another. 3. The power of discriminating the relative cool- ness of two stimuli, or the relative warmth of two hot tubes may be diminished. Thus 20° C. may be said to be the same as ice, although both are uniformly called cold, and 40° C. may seem as warm as, or even warmer than 48° C. The faculty of appreciating the relation to one another of two temperatures on the same side of the scale is disturbed. For recognition of posture and for passive move- ments they found that: 1. Cortical lesions most frequently disturb the recognition of posture and of passive movements. Whenever sensation is in any way affected in conse- quence of a cortical lesion these two functions suffer. 2. In all their cases the distubrance in the faculty of recognizing posture and passive movements was greater toward the peripheral parts of the affected limb. 3. When a patient with unilateral disturbance of these faculties attempts to point to some part of his body, defective knowledge of its position causes greater error than want of recognition of posture and movement in the hand with which he points. 4. When testing the patient's power of appreciat- ing passive movement, the answers are frequently uncertain and hallucinations of movement may occur. And yet the patient may be remarkably consistent and accurate when normal parts are tested. 5. Localization tests showed: (a) The power of localizing the stimulated spot is not infrequently preserved, although sensation may !»■ otherwise disturbed as a consequence of cortical lesions. (b) This faculty is independent of the power of recognizing the position of the affected limb; appre- ciation of posture may be lost, although localization is not in any way diminished. 362 (c) If the power of localization is lost, the patient will be unable to recognize not only the position of a spot touched but also the position of a prick. (d) When localization is defective in consequence of cerebral lesions, the patient docs not habitually localize in any particular direction, but ceases to be certain where he has been touched or pricked. 6. The compass test revealed that: (a) A cortical lesion may destroy the power of discriminating two compass points, both when applied simultaneously and collectively. If this is the case, no threshold can be obtained for either form of the test; increasing the distance be- tween the points does not constantly improve the accuracy of the answers. (b) This disturbance is not caused by changes in tactile appreciation; for it can be demonstrated equally well with two painful as with two tactile stimuli. (c) The condition of tactile sensibility and the accuracy of the simultaneous compass-test are cloi elj associated; a disturbance of the tactile threshold is usually accompanied by a raised threshold for the appreciation of two points applied simultaneously. (d) Should the power be preserved of recognizing two points when the compasses are applied consecu- tively, localization will be found to be intact. The patient's appreciation of the two points when they are separated by an interval of time is due to the recognition of the separate locality of the two spots touched. 7. Appreciation of weights showed that: (a) The power of estimating the relative of two objects of the same size and shape is readily disturbed by cortical lesions. (6) Though the patient may retain sensations of contact when the weight is placed in his hand, all power of recognizing the relative heaviness of the object has disappeared. (c) This faculty is equally disturbed in most cases whether the weights are placed on the supported or the unsupported hand. From these and related studies, it would appear that sensory impulses pass from the thalamus to the cortex is five groups: 1. Those concerned with the recognition of posture and passive movement. If these impulses are affected the power of discriminating weights on the unsupported hand may be also diminished. 2. Certain tactile elements; integrity of this group is necessary for the discrimination of weights placed on the fully supported hand. 3. Those impulses which underlie the appreciation of two points applied simultaneously (the compass test); on this group also depends the recognition of size and shape. 4. Those which underlie the power of localizing the situation of a stimulated spot. Recognition of the double nature of two points applied consecutively also depends on this group of impulses. 5. All thermal impulses are grouped together to underlie a scale of sensations with neat at the one end and cold at the other. At the level with which we are now dealing these impulses have already ex- cited the affective center and are passing away to the cortex. Head and Holmes believe that the functional integrity of the cortex enables attention to be con- centrated upon those changes which are produ 1 by the arrival of afferent impulses. When this is disturbed, some impulses evoke a sensation, but others from lack of attention, do not affect consciousness. Attention no longer moves freely over the sensory field to be focussed successively on fresh groups of sensory impressions. Sensations, once evoked, are not cut short by the moving away of the focus of attention as when cortical activity is perfect. Hence arise persistent sensations and hallucinations which REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, General Surgical are so prominent a feature after lesions of the cortex. They believe that the cerebral cortex is tin- organ 1 ,y which we are able to foi i ition upon changes evoked by sensory impulses. A pure cortical lesion, which is not advancing or causing periodic discharges, will change the sensibility of the affected - in such a way that t he patient 's answers appear to be untrustworthy. Such diminished power makes the estimation of a threshold in many cases impossible. Uncertainty of response destroys all power of comparing one set of impressions with another and so prevents discrimination. ;.: addition to its function as an organ of local attention the sensory cortex is also the storehouse of past impressions. These may rise into consciousness as images, but more often, as in the case of spacial impressions, remain outside central consciousness. Here they form organized models of ourselves which may be termed "schemata." Such schemata modify the impressions produced by incoming sensory im- pulses in such a way that the final sensations of position, or of locality, rise into consciousness cha with a relation to something that has happ before. Destruction of such "schemata" by a lesion of the cortex renders impossible all recognition of posture or of the locality of a stimulated spot in the affected part of the body. In daily life all stimuli excite more or less both thalamic and cortical centers, for most unselected itions contain both affective and discriminative elements. But, among the tests employed in sen- sory analysis, some appeal almost entirely to the one or the other center. The test for recognition of posture, as carried out by Head and Holmes, is purely discriminative; while the pain produced by dug the testicle, or to a less degree by the pressure algometer, appeals almost exclusively to the more affective center. - nsory impulses arriving at the optic thalamus are regrouped in such a way that they can act upon both its essential center and the sensor}- cortex. The itial organ of the thalamus is excited to affective activity by certain impulses, and refuses to react to those which underlie the purely discriminative aspects of sensation. These pass on to influence the cor- tical centers where they are readily accepted. In a similar way. the primary centers of the cortex cannot receive those components which underlie feeling tone: in this direction they are completely blocked. It has long been recognized that sensations are endowed with feeling tone to different degrees. In those which underlie postural appreciation this quality is entirely absent, while visceral sensations are, in some instances, little more than a change in a general feeling tone, one set of impulses appeals almost exclusively to the cortical center, the other to that of the optic thalamus. All thermal stimuli, however, make a double appeal. Every sensation of heat or cold is either comfortable or uncomfortable; the only entirely indifferent temperature is one that is neither hot nor cold. In the same way. some unselected tactile stimuli appeal both to the sensory cortex and to the optic thalamus. For not only is a touch always related to, and distinguished from, something that has gone before it, but we have shown that contact, especially of an object moving over hair-clad parts, is capable of exciting thalamic activity. Vibrations of the tuning fork also make a double appeal, for when the cortical paths are cut the amplitude of the vibration must be greater in order that it may be appreci- ated; on the other hand, the vibratory effect may be stronger on the abnormal side in those thalamic cases where the affective response is excessive. But these two centers of consciousness are not co- equal and independent. Under normal conditions the activity of the thalamic center, though of a dif- ferent nature, is dominated by that of the cortex. When we examine ttion normally prod by a prick, we rei ■ , lops slowly and lasts a considerable time after the stimu- lus has ceased. Moreover, the same intensity of stimulation will produce a different effect 01 same spot on different occa ions. A long, latent and want of uniformity, are char- acteristic of all painful Si This is seen in an exaggi rat d form in cases "her.- the thalamic center has been freed from control. The to prick is slow, but persists long after the stimulus has ceased. Moreover, the reaction when it occurs, tends to be explosive; it is as if a spark had fired a magazine and the consequences were not commensurate with the cause. On the contrary, the sensations normally prodt by moderate tactile stimuli are characterized by a short latent period, and disappear almost immediately on the cessation of the stimulus! A lesion of tic sory cortex disturbs both these characteristics. Tactile sensations become uncertain and incalcu'able, and no threshold can be obtained; persistence and hallucinations mar the uniformity of the records. Now we have shown that the sensory cortex is the organ by which attention can be concentrated on any part of the body that is stimulated. The focus of attention is arrested by the changes produced by cortical activity at any one spot. These are sotted out and brought into relation with other sensory processes, past or present. Then the focus of atten- tion sweeps on, attracted b} 7 some other object. All stimuli which appeal to the thalamic center have a high threshold. They must reach a high intensity before they can enter consciousness, but once they have risen above the threshold they tend to produce a change of excessive amount and" dura- tion, and this it is the business of the cortical mechan- ism to control. The low intensity of the stimuli that can arouse the sensory cortex, and its quick reaction period, enable it to control the activity of the cumbersome mechanism of the thalamic center. The view of the sensory mechanism put forward in their paper explains many of the facts already recog- nized by both psychologists and clinicians. It enables us to understand how integrations can occur at all afferent levels of the nervous system, and makes development possible even in the individual. The aim of human evolution is the domination of feel- ing and instinct by discriminative mental activities. This struggle on the highest plane of mental life is begun as the lowest afferent level, and the issue becomes more clearly defined the nearer sensory impulses approach the field of consciousness. Smith Ely Jelliff!:. Anesthesia, General Surgical. — Anesthesia (apaur- thpla) may be defined as loss of feeling or sensation, and general surgical anesthesia, with which this arti- cle deals, as loss of feeling or sensation in the entire organism during any surgical procedure, caused by introduction into the blood of an anesthetizing agent. It is impossible to say at what time in human his- tory attempts were first made to relieve pain and suf- fering. Certain it is, however, that the Assyrians and the Egyptians were familiar with substances cap- able of producing soporific and anodyne effects. Homer, Herodotus, Dioscorides, Pliny, and many other ancient writers frequently referred to such sub- stances. Shakespeare also frequently mentioned an- esthetizing draughts, but the production of surgical anesthesia, as we now understand it, is a matter of quite modern development. During the early part of the nineteenth century considerable attention was given to the anesthetic properties of nitrous oxide and ether by different observers, but no satisfactory and practical applica- 363 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tion was made in the induction of general surgical an- esthesia till December, 1S44, when Horace Wells, a dentist of Hartford, Connecticut, demonstrated the anesthetic properties of nitrous oxide by having one of his own teeth extracted while he was insensible through the inhalation of this gas. Further experi- ence with the use of this anesthetic convinced Wells that painless tooth extraction was both possible and practical, but after an unfortunate failure in a dem- onstration at the Harvard Medical School this use of nitrous oxide was generally, but undeservedly, discredited for several vears. On September 30, 1846, \V. G. Morton, a dentist of Boston, employed ether vapor in anesthetizing a patient for tooth extraction, and thereafter admin- istered it for surgical operations with complete suc- cess. The use of this agent rapidly spread and it was soon quite extensively employed in America, Great Britain, and on the Continent. On November 10, 1847, Sir James Simpson an- nounced the discovery of the anesthetic properties of chloroform and, on account of Simpson's influence and of the more rapid action and less irritating and disagreeable vapor of the drug, chloroform began rap- idly to supplant ether in general surgery. However, in a few weeks after its first use a fatality was reported, and from time to time similar casualties occurred, until finally it became quite apparent that whatever advantages the new agent seemed to possess its anes- thetic use was not without considerable danger to life. In 1847 Heyfelder first administered ethyl chlor- ide for a surgical operation, and successfully demon- strated its anesthetic properties; but it did not pax into general use until about fifty years later. It will thus be seen that surgical anesthesia and the anes- thetic properties of nitrous oxide, ether, chloroform, and ethyl chloride all were discovered within a short period of three years; and in the three-quarters of a century that has since elapsed, although replete with research, experimentation, and synthetic produc- tion, no widely used inhalation anesthetic has been discovered or evolved, so that the four agents above mentioned, used either singly, in sequence, or in com- bination, hold practically undisputed sway in this great and important field of modern medicine. The Physiology of General Anesthesia. — Gen- eral anesthetics affect all the various systems of the organism in a more or less characteristic manner. There is a distinct difference, however, in the effect produced by each of the general anesthetics in the same organism, no matter by what means or manner the anesthetic may be introduced. Furthermore, the same subject displays different phenomena under the influence of the same anesthetic with only a difference in the method of administration. Finally, subjecl . seemingly essentially similar, display markedly differ- ent phenomena under the same anesthetic and iden- tical system of administration. It will be readily in- ferred from a consideration of these facts that the selection of the anesthetic and the practical applica- tion of a method of administration that will secure the desirable phenomena and avoid the undesirable, in any individual subject, are matters that present no small amount of difficulty. Nitrous Oxide. — As nitrous oxide when inhaled pure readily combines with hemoglobin, producing a dark colored blood on account of the cells being deprived of oxyhemoglobin, it rapidly causes cyanosis as well as loss of consciousness and sensation. Inasmuch as the cyanosis and anesthesia are intimately associated when only nitrous oxide is inhaled, it was formerly thought that the anesthesia was due to the cyanosis or asphyxiation. However, Edmund Andrews of Chicago, in 1868, conclusively proved, by the sim- ultaneous administration of pure oxygen, that nitrous oxide possessed distinct anesthetic properties separate and apart from its asphyxial phenomena, 36 1 and that anesthesia might be secured with it when mixed with sufficient oxygen to maintain a normal color. The initial sensations of nitrous oxide are of an agreeable and stimulating character, as is the case with the other general anesthetics, and, with oxygen excluded, anesthesia and cyanosis rapidly follow, to- gether with jactitation, stertor, respiratory depres- sion, muscular spasm, and finally respirator}' failure all usually in the order mentioned. Under nitrous oxide anesthesia the amount of car- bonic acid in the blood is less than during anesthesia produced by the other general anesthetics, but accord- ing to investigations thus far reported it produces no permanent effect upon the cells or other constitu- ents of the blood. Arterial tension, however, is slightly raised by the action of this anesthetic. As nitrous oxide is unirritating it causes no pathological change in the cells of the tract of its administration and elimination, or degenerating effect upon the cells of the liver, kidneys, or brain. Its toxicity, therefore, is very low indeed. Ether.— One of the leading characteristics of ether is that it is a very energetic stimulant to the respira- tory, circulatory, nervous, and glandular systems. Its vapor is irritating to the respiratory passages, often causing the secretion of considerable mucus and saliva. As is the case with nitrous oxide, its effects are greatly increased by the limitation of oxygen. In ether toxemia respiratory failure precedes that of the circulation. The effect upon blood pressure is prob- ably nil, as some observers claim that it increases it, while others claim it produces a slight fall in arterial tension. The blood changes under ether anesthesia are quite important and far reaching, affecting detrimentally, both the quantity and quality of the blood constitu- ents. The volume index shows an immediate loss which is not regained till after the seventh day. The color index shows an almost constant drop beginning during or immediately after anesthesia and continu- ing till the fifth or sixth day. The most important blood effect, however, is upon the leucocytes, for while it produces a leucocytosis it decreases the functional activity of the phagocytes, and in this manner very materially lowers the patient's resisting power against infection. In addition to its degenerative effect upon the cells of the blood ether likewise causes a pathological change in the cells of the brain, liver, and kidneys. and decreases the secretion of urine as to both its watery and nitrogenous elements. The pathological change in the brain cells induced by ether is undoubt- edly one of the leading factors in the depression and shock that follow every ether anesthesia of any con- siderable duration or depth. Chloroform. — In common with the other general anesthetics chloroform at first stimulates respiration, but as narcosis becomes established the breathing is quiet and shallow, and under full effect respiratory paralysis follows. It is a mistake to believe that chlo- roform always produces fatality by primary cardiac failure, for in true chloroform toxemia the heart may continue to beat after respiration has ceased, although one of the leading causes of such respiratory failure is a circulatory effect, viz., a fall in arterial tension. Chloroform produces a dilatation of the whole car- diovascular system. Circulatory paralysis, or sud- den heart failure, however, is due to the use of a loo concentrated vapor, for if precaution is taken to avoid this the heart continues to beat after respiration ceases. What really constitutes a too concentrated vapor, or overdosage, is a matter that varies consider- ably, but depends more upon the depth of res- piration than upon any other factor other than the percentage of vapor. Most of the fatalities with chlo- roform have occurred during the induction of anes- thesia, and often by the patient simply making a REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia! Genera] Surgical deep inspiration of a vapor, which, with an ordinary inspiration, would doI have been too concentrated, and, therefore, would not have been an overdosage, Chloroform product's more destructive changes in the cells of (he blood and liver, and less in the e oreting cells of the kidneys, than does ether. The degenerative visceral effects of chloroform are very pronounced, especially upon the liver, and when taken in connection with the immediate fatalities the com- plete mortality is very high indeed. Ethyl Chloride. — In physiological action ethyl chlo- ride more nearly resembles nitrous oxide than any other general anesthetic. It first stimulates respira- tion and rapidly causes loss of consciousness, muscular spasm, stertor, and cardiac paralysis. It affects the cardiovascular system in very much the same manner as chloroform, by causing a fall in blood pressure, and death occurs either directly or indirectly through its effect upon the circulatory system. Its effects upon the blood, brain, and viscera have not as yet investigated. SELECTION OF THE ANESTHETIC AND METHOD OF Administration. — The anesthetist of the present day has at his disposal the four primary inhalation anesthetics, a number of mixtures and combinations of these agents, a number of sequences, and a large variety of methods of administration, and each has its special advantages. In the selection of the anesthetic, as well as in the determination of the method of administration, the primary consideration should be the safety of the Satient, but unfortunately this is not always the case. [ere convenience or a slight difference in cost should not for a single moment be weighed against the patient's safety while on the operating table or welfare during the period that should be one of convalescence. Selecting a particular anesthetic and method of administration on the basis that it is safe in the hands of the unskilled, as is so often the case, is unscientific and belongs to a bygone age The surgeon never recommends a particular method of operation because, perchance, it is safe in the hands of the unskilled! Why then, the question may well be asked, is the literature of to-day so replete with the advocacy by surgeons themselves of a particular method of administering ether because it is safe in the hands of the unskilled? Such practice is a stigma upon the whole profession. If any other method or any other anesthetic is safer and better for the patient, the necessary skill for its proper administration will be forthcoming just as soon as the surgeon makes a real demand for it. It is not a valid or scientific criticism or objection against any anesthetic or method that its use requires skill. It is a very difficult, if not impossible, matter to determine the real mortality of the different anes- thetics. The personal factor of the anesthetist is more important than the anesthetic or method, so even if individual statistics were accurate, which is usually not the case, they would be very misleading. Besides, as a rule, statistics cover only the immediate mortality, while the remote effect and its accom- panying mortality, which with some of the anes- thetics is high, is disregarded. Practically all authorities agree that nitrous oxide is the safest anesthetic known for the induction of anesthesia, and the mortality for this particular form of administration is very low indeed, being given by \Yood at 1 in 1,000,000. For prolonged administra- tion oxygen must be combined with nitrous oxide, and while this combination is safer than nitrons oxide alone, the mortality during prolonged use is much higher than in brief administrations, though it is very generally considered to be less than that of ether. Certain it is that when the innocuous effect of nitrous oxide-oxygen is considered, the entire absence of any irritation of the respiratory and genito- urinary tracts and of degeneration of the cells of tli. 1 blood, brain, liver, and kidneys, together with its shock-preventing and immunity-preserving quali- ties, show that its real or total mortality is decidedly less than (hat of el her. It is quite certain that ether ranks second a to safety. Its mortality is usually given a- I in 16,000. Such statistics, however, cover only the immediate mortality, and, when in connection with this the remote mortality is considered, tin' real or total mortality is much higher than the figure just given. The mortality of chloroform is usually given as 1 in 4,000, leit tic real or total mortality, a- i- the case with ether, is much higher than the stati tics thai cover only the immediate mortality indicate. The mortality of ethyl chloride is generally placed between that of ether and chloroform, or about I in in. null. As ethyl chloride is used chiefly to induce anesthesia, and it is for this form of administration upon which this rate of mortality is based, it is evident that for such use it is many times more dangerous than nitrous oxide. As the majority of deaths that are given in statis- tics occur in the induction stage, it is quite evident that the patient's safety demands that nitrous oxide be used as the preliminary anesthetic; also that for this purpose ethyl chloride is much safer than chloroform. Difficulties and Dangers of General Anes- thesia. — The immediate danger to the life of the patient inhaling an anesthetic is connected with the respiratory and circulatory systems. Either system may be the one primarily affected, but the other one soon becomes involved, so that it is usually a complex state when the patient's condition is serious. Respiratory failure may be classified under two general heads: (1) Obstructive, (2) central. The obstruction to respiration may arise: In the mouth by the lips being drawn together during inspiration; in the nose by polypi, spurs, malforma- tion, tumors, etc., and if the mouth and lips are tightly closed there may be complete obstruction to the respiratory movement. At the beginning of the administration the obstruction may be only partial, but on account of the attending congestion and swelling of the mucous membrane, it may later on become complete. The tongue, increased in size on account of conges- tion, may cause obstruction simply on account of its abnormal size, or, as is more often the case, it falls backward, thereby causing more or less complete obstruction. Morbid growths of the tongue, palate, tonsils, pharynx, and epiglottis and foreign bodies also offer more or less obstruction to the respiratory movement. Excessive secretion of mucus may produce considerable obstruction. Spasm of muscles about the neck, jaw, and of the glottis may produce complete and sudden arrest of respiration. Keflex stimulation by operative procedure, distention of the abdomen producing upward pressure on the dia- phragm, or position of the patient on the operating table producing the same effect, and distention of the pleural cavities with fluid alter or obstruct normal respiration. Respiratory failure from central cause may be due to an overdose of the anesthetic, loss of blood, or shock. This form of failure usually develops insidi- ously, and is more difficult to treat. The most common form of sudden and temporary respiratory arrest occurs with the act of vomiting, and this in itself is not serious. However, if the vom- it ns is not immediately and completely wiped away, it may, during inspiration, be aspirated into the trachea and thus cause complete respiratory obstruc- tion, or, by the conveyance of infection, be the direct cause of a subsequent pneumonia. In the treatment of respiratory obstruction, arrest, 365 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES or failure the cardinal principle, of course, is to re- move the cause, and this usually is not a difficult matter if the cause is only recognized. The anesthe- tist must be ever alert to detect the indications of the various cause,-, of respiratory embarrassment. In the induction stage, or during incomplete anesthesia, too great concentration of the vapor is the most frequent cause of holding the breath and of spasm of various muscles concerned in respiration. If the spasm is not severe, the temporary withdrawal of the anesthetic is usually sufficient; but if this does nut relieve the condition the jaws should be widely Fig. 203.— Hard Rubber Oral Screw. opened with a wedge, a gag inserted, the tongue grasped with a pair of forceps, and traction used, at the same time intermittent compression being made upon the chest, or actual artificial respiration being resorted to; unless the spasm is unusually severe these means will quickly restore nor- mal breathing. Tracheotomy will always afford the desired relief, unless its use is too long deferred, and if the spasm is very severe, and jaws closed and rigid, it is practically the only available effective treat- ment. If the tongue falls back against the posterior wall of the pharynx, the patient's head should be turned to one side and the angle of the jaw pressed for- ward. In case it is necessary to keep the jaw thus pressed for- ward, or whenever such a position does not completely relieve this source of obstruction, a Coburn "breathing tube" (Fig. 204) should be quickly placed in position. This tube is specially moulded with a curve adapting it to be slipped over the base of the tongue, and car- dioxide in the blood. Accordingly whenever respira- tion needs stimulation no more effective or practical respiratory stimulant can be used than carbon dioxide. This may be administered from two sources, allowing the patient to rebreathe his own exhalations, or add- ing pure carbon dioxide direct; am! with the carbon dioxide utilized from either source pure oxygen should be added. A very practical method, other than the rebreathtng, is to administer from a cylinder a mix- ture of ten per cent, carbon dioxide and ninety per cent, oxygen. Hypodermics of atropine and a heart stimulant, preferably adrenalin, with either caff, ine camphor, or alcohol, may also be used. If these means fail pharyngeal or intratracheal insufflation of air or oxygen is the last resort. If there is a sudden respiratory arrest, artificial respiration by Silvester'a method must be maintained until the patient inspires sufficient carbon dioxide to stimulate the respiratory center, but if the patient does not respond to tins treatment properly the insufflation should not be too long delayed, or else circulatory failure may supervene as well. It is important always to bear in mind that mere movement of the chest does not necessarily indicate actual respiration, and in all doubtful cases the anesthetist must immediately make absolutely sure whether there is a true respiration or not. In some 1' ig. 204. — Coburn 's Breathing Tube. ries a metal fitting at its outer end which fits between the teeth, holding it in position and preventing it from being closed during incomplete relaxation of the jaws. The curve facilitates its introduction and keeps it patulous. The tube is ample in size for full and free respiratory movement, and presents no interference with the application of any face mask. When respiratory failure is due to central cause the treatment is radically different. Henderson, with his revolutionizing theory of carbon dioxide, has shown that the great controller of respiration is the carbon 366 Fig. 205. — Pozzi's Tongue Forceps. methods of administration this matter is difficult to ascertain. The Coburn apparatus has an automatic indicator which always shows whether the patient is actually breathing, no matter what anesthetic is used or what method is employed. Circulatory failure may be either gradual or sudden. In gradual failure of circulation there is usually ample warning. The patient becomes pale, eyelids separate, pupils dilate, lips and finger-tips become slightly cyanotic, pulse is fast and feeble, nose is "pinched," cold sweat comes out on the forehead, and the pulse finally becomes imperceptible at the wrist or about the head. Whenever there is marked weakening of the pulse appropriate treatment is imperative. Before insti- tuting treatment, however, the anesthetist should quickly make sure of the exact condition of the pa- tient. If the corneal reflex is abolished the anesthetic should be withheld for a short time at least. If the anesthesia is light and there is any tendency toward vomiting the anesthesia should be deepened. An absolutely free air-way should be immediately secured ami good oxygenation maintained. A change in anes- thetic or method may be desirable. The patient's head should be kept low. Hypodermics of ergotol (large amounts) and of camphor or caffeine may be administered. A very effective treatment is a saline infusion of 1,000 c.c. to which has been added about forty minims of adrenalin solution, even though there has been no considerable loss of blood. The admin- isl ration of carbon dioxide and oxygen stimulates res- piration and vascular tonus and thereby indirectly greatly improves the circulation and is the most effective single treatment for this condition, unless the anesthetic itself is exerting a direct inhibitory REFERENCE HANDBOOK OP THE MEDICAL SCIENCES Amnesia, General Surgical action upon the heart, when, of course, a change in the anesthetic is imperal ive. In sudden circulatory failure the anesthetic be discontinued and the patient immediately inverted nearly as possible, and carbon dioxide-ox administered, using :ui ili nit rou oxide. < >r in other words ether prod id four times as much shock as nitrous oxide a very important scientific matter, as , hock is a feature of every surgical operation. Practically all critical observers agree thai in infection the toxemia is decidedly more pronounced after ether or chloroform anesthesia than after that of nitrons oxide. Graham Shows that chloroform and ether markedly impair phagocytosis, and thereby demonstrates the scientific basis of the previously observed clinical facl . Pneumonia and bronchitis are sequels of general anesthesia, most frequently Observed after ether and least frequently after nitrous oxide. The explana- tion of this difference is to be found in the irritant qualities of ether vapor, and in the fact that the resulting anesthesia markedly lowers the patient's resistance against infection. lEMflfJNSCC.N V Fig. 208. — Mussey's Mouth Gag. The irritant action of ether upon the kidneys and genitourinary tract and the degenerating effect of chloroform upon the liver contraindicate these agents whenever these organs are involved. It has recently been shown that ether also produces a degenerating effect upon the liver, and that chloroform likewise affects the kidneys. In diabetes nitrous oxide is always strongly indi- cated as the anesthetic, as coma much more frequently follows the administration of ether and chloroform in this condition. Role of Carbon Dioxide.- — Dr. Yandell Hender- son, of the Yale Medical School, in his remarkable Fig. 209. — Cusco's Tongue Forceps. work on carbon dioxide, has startled the entire scientific world with his demonstrations of the vast role that carbon dioxide, heretofore considered practi- cally an insignificant waste-product, plays as a regu- lator of so many of the vital functions of the human body. His work is reported mainly in a series of papers published in the American Journal of Physi- ology, and I can here make only a brief summary 367 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ami quotation of the more important features that pertain to anesthesia. Respiration. — The great regulator of respiration is nut an automaticity of the respiratory center similar to that of the heart, or afferent nerve influences, or need of oxygen, but the amount of CO, in the blood. The respiratory center requires a continuously acting stimulant to force it into constant activity. The afferent impulses, under ordinary conditions, affect only the rate or depth of respiration and not the amount of pulmonary ventilation. Whenever pul- monary ventilation is increased, the amount of CO, in the arterial blood is thereby decreased, i.e. acapnia results. "Perhaps there is no idea more firmly fixed in the medical mind, or which it will be harder to root out, than that the respiratory center is sensitive to alterations in its oxygen supply. Yet during the past few years it lias been ((inclusively demonstrated that within wide limits the respiratory center is indifferent both to excess and to lack of oxygen. It should be added, however, that this statement needs modification, so as to admit that conditions which result from anoxhemia do irritate the center. These conditions, however, are produced slowly and in the tissues, not primarily in the center. Even to a total lack of oxygen the respiratory center makes no immediate response, although it may be killed thereby. " The crucial experiment in this field is that of voluntary forced breathing. The experiment is so simple and easily performed, at any time, by any one, that it ought to become universally familiar. It is only necessary to breathe as rapidly and as deeply as you can (for several minutes) Thereby you will induce in yourself a moderate degree of acapnia. When you cease the voluntary effort you may find that your hands are temporarily paralyzed. Your legs and arms may be asleep. You may shiver as in a chill. You will feel strangely lightheaded If your efforts have been sufficiently energetic and a considerable degree of acapnia has been induced, when you stop forcing yourself to breathe you will stop breathing alto- gether. In this respect the respiratory center is automatic. If you nave previously reduced your store of CO„ sufficiently, you will remain breathless and without any desire to breathe, until you turn blue in the face," thereby demonstrating that it is not the lack of oxygen but the amount of CO, in the blood that is the essential factor in respiratory control. Circulation. — The carbon dioxide content of the blood exerts far-reaching effects upon the circula- tion by its control over venous pressure. A decrease from normal of the CO, in the blood causes loss of venous tonus, and thereby lowers venous pressure — an essential phenomenon in shock. "Both Crile and llnmberg and Passler concluded (correctly, I believe) that in shock the circulation fails in the same manner as after hemorrhage, and that the heart fails because too little blood is supplied to it through the veins. Both found that intravenous infusion restored for a time normal arterial pressure and heart action. Unfortunately both labelled this true picture with the misleading formula — the only formula for it offered by current physiology — vasomotor failure. Present knowledge regarding the vasomotor nervous system indicates that its control is exercised — mainly at least — upon the finer branches of the arterial system Now the failure of vascular tonus in traumatic and toxemic shock is almost wholly in the venous system. Both Crile and Rom- berg and Passler saw and emphasized this fact. It seems not to have occurred to them that they were dealing with the failure of a mechanism as yet un- recognized in physiology. In this; they were in it alone. For half a century physiologists have been so dazzled by Claude Bernard's discovery of the vaso- motor nervous system that they have neglected to 368 emphasize the fact that the circulation must involve a third factor in addition to the heart and the per- ipheral resistance of the arterial system. Otherwise it would be as unstable as a stool balanced only on two legs. It must include a mechanism, or mechan- isms, regulating the volume of the blood, and deter- mining the venous supply to the right heart. It is 1 1 1 i — ; venopressor mechanism, I believe, and neither the heart nor vasomotor nervous system, which is the essential element in the failure of the circulation in shock. " It is so easy to record arterial pressure and so difficult to measure the minute volume of the arterial blood stream that one is inclined to forget that the pressure in the arteries is really a phenomenon of only secondary importance The primary func- tion of the circulation is the volume of blood pumped onward by the heart in unit time The heart can discharge during systole only so much blood as distends its chambers during diastole. The diastolic filling of the right heart depends upon the volume of the stream flowing to it through the veins and upon the distending pressure which this stream affords. Venous pressure, is, so to speak, the fulcrum of the circulation. " The respiratory center, by regulating the CO, content of the arterial blood within narrow limits of variation, exerts an indirect but powerful control of the venopressor mechanism. Any considerable accumulation of CO, above normal augments the venous pressure. Excessive pulmonary ventilation tends to lower it. Acute acapnia diminishes the volume of the blood as effectually as does an extensive hemorrhage." Henderson was able to produce all grades of severity of shock in animals by excessive artificial respiration, the increased pulmonary ventilation causing acapnia. " Voluntary forced breathing in man, so far as the experiment can be carried, induces symptoms similar to those of shock. Death from failure of respiration would probably result from vigorous voluntary hyperpnea for fifteen to twenty minutes. Pain, ether excitement, sorrow, fear, and other con- ditions inducing shock, involve excessive respiration. " Excessive artificial respiration, applied to dogs for twenty-five to thirty minutes, is followed by apnea so prolonged that the heart fails, after seven to eight minutes, for lack of oxygen. The inactivity of the respiratory center is solely due to the depletion of the body's store of C0 2 Administra- tion of CO, gas during apnea induces an immediate return to natural breathing. Administration of oxygen by the Volhord method affords ideal condi- tions for recovery from acapnia, and prevention of asphyxial acidosis." The dangers of anesthesia that are concerned in the acapnial theory are thus summarized by I tenderson: " 1 . Anesthetics tend to prevent shock because they diminish pain-hyperpnea, and thus obviate the de- velopment of acapnia. "2. Respiratory excitement during the initial stages of anesthesia diminishes the C0 2 content of the blood, and thus tends to induce a subsequent failure of respiration. " 3. Morphine raises the threshold for CO, more than it does the afferent threshold of the respiratory center. Chloroform elevates the latter threshold more than the former. Ether in quantities short of pro- found anesthesia exerts a respiratory stimulant in- fluence which lowers the threshold for C0 2 , and thus tends to induce acapnia. "4. Apnea in anesthesia depends, in the same manner as in normal life, upon the relation of the level of the threshold of the respiratory center for CO, to the quantity of CO, in the blood and tis- sues. Whenever the former is above the latter, spontaneous breathing ceases. IiEKKUKXCK HANDBOOK OK THE MEDICAL SCIENCES Anesthesia) General Surgical "5, Under anesthesia the threshold for Co.. may be elevated fifty per cent, above normal, or depressed fifty per cent, below normal. Such a depression of the threshold causes vigorous hyperpnea. If Inns,' continued, it results in intense acapnia. ■•~ii. Chloroform apnea may be regarded as merely a form of apnea vera. "7.' Experiments show thai ether-hyperpnea is quite fective as pain-hyperpnea as u means of inducing a suoscqui nt fatal apn> a r, ra. Kg, in normal subjects under chloroform respi- ration always fails before the heart. Subjects which passed through a period of sickness and suffering, or tin ir experimental equivalent, are hyper-susceptibli to the toxic influences of chloroform.* In uchca es the circulation failsfirst, or simultaneously with respiration. i. Hypercapnia during anesthesia may be the factor which determines the development of chlor- oform necrosis. "10. Skilful anesthesia consists in maintaining the threshold of the respiratory center for CO s al a \ normal level, and in avoiding the developmenl either of acapnia or of hypercapnia." The Signs and Stages of Anesthesia. — For enience of description the phenomena of anes- thesia are usually divided into four stages: 1. The first stage extends from the beginning of the administration to complete loss of conscious- ness. The phenomena observed in this stage arc dependent largely upon the manner of administration and the character of respiration. If the anesthetic is cautiously and skilfully administered, and the patient breathes fully and regularly, the induction is doI disagreeable, but if the anesthetist is unskil- ful the first stage is distinctly unpleasant, especially if the patient is nervous or becomes excited, and ether or chloroform is the anesthetic. With such quickly acting anesthetics as nitrous oxide and ethyl chloride this stage is very short and the pa- tient usually experiences no unpleasant sensations. During this period the room should be kept as quiet as possible, conversation being especially prohibited. During this stage there is increased cardiac action with a rise in blood pressure, and respiration is in- ised in frequency and depth unless modified by emotional disturbances or irritant action of the anesthetic vapor; the pupils are dilated. 2. The second stage extends from the loss of consciousness to the loss of the corneal reflex, and is otherwise known as the stage of "struggling," for during this period many patients, especially those addicted to alcohol or to smoking, struggle more or less violently. While assistants should be at hand to prevent self-injury if the patient strug- gles, yet the patient should never be forcibly re- strained as that increases the tendency to struggle. The limbs are often rigidly extended, respiration is temporarily suspended "through contraction of t ho muscles controlling respiratory movement, and the jaws are at the same time firmly clenched. The respirations become deeper and more frequent unless impeded by muscular spasm, deglutition, etc. Heart action is still further increased, much depending, however, upon respiration. It is in this stage, espe- cially if there be struggling and holding of the breath, that chloroform becomes so dangerous, for when there has been no breathing for several seconds and a deep inspiration is taken, as is often the case, sufficient chloroform for a fatal overdose may be inhaled and ab- sorbed even though the strength of vapor would have been tolerable under normal respiration. With ether the patient's skin will be flushed, and the secretion of mucus and saliva increased. The pupils are smaller than in the first stage. 3. The third stage, otherwise known as the stage of surgical anesthesia, begins with the loss of the * The italics are mine. Vol. I.— 24 corneal reflex. The muscular rigidity of the second stage disappears in the third stage, but more quickly under chloroform than under ether or nitrous oxide. Under ether the patient is more florid, if there is ufficienl oxygenation, the secretion of mucus and saliva is still further increa ed, and the circulation still further stimulated. If chloroform is being ad- ministered it is of the Him" I importance thai there should be good oxygenation of the blood, so evidences of pallor or of cyanosis, especially about the lips and cars, should be closely watched, as even mild asphyxia greatly increa e the depre ing effect of this anesthetic. Accordingly it is of the utmost im- portance that the air-way be open and respiration free and not obstructed in any way whatever when- ever chloroform is being administered. The color of the face, more especially of the lips and ears, is a reliable index of oxygenation. The character of the respiration is perhaps the most important single guide in the maintenance of the proper degree or depth of anesthesia. The rhythm in this stage is regular under all anesthet- ics, increased in frequency and depth under nitrous oxide and ether, and somewhat decreased in these respects under chloroform. At the time of mak- ing the initial incision the anesthetist should notice if this procedure alters the respiratory movement in any way, and if it does, the anesthesia should be immediately deepened. A careful watch should be at all times kept of the respiration, as slight changes in it will forewarn the experienced administrator of impending danger. The anesthetisl musl not only know that air is passing into and out of the lungs, mere movements of the muscles of respiration not being sufficient, but he must also know about what the volume is. If the breathing in this stage becomes quiet and shallow it is because the anesthesia is cither too light or too deep. If the former, the lid and corneal reflexes will be present and more of the anesthetic should be administered; if the latter, the pupil will be widely dilated and the lid and corneal reflexes abolished, and the administration should be held in abeyance temporarily. The pulse in the third stage also settles down to a regular rhythm and volume, increased in both re- spects under nitrous oxide and ether, and slightly decreased under chloroform. The pulse should be taken at frequent intervals, as sudden changes may take place at any time in both heart action and blood pressure. As the operation proceeds the tendency is for the pulse to increase slightly in frequency and decrease in volume, but any considerable change in these respects demands attention, as shock may be developing. The pupil is of value in determining the depth of anesthesia ordinarily only when there has been no preliminary hypodermic medication that affects its size. As the tendency to the use of such medi- cation is increasing, and rightly so, less and less attention is being given to the size of the pupil; although it is a very delicate indicator when no such medication has been used, yet it is not at all essential. In the surgical stage the average size of the pupil under ether is about 4 mm. in diameter, and about 2.5 mm. under chloroform. A contracted pupil indicates a light anesthesia, while a dilated pupil indicates cither a light or a deep anesthesia. When it is dilated under a light anesthesia, the lid and cor- neal reflexes are present and the dilatation is due to reflex stimulation by the operative procedure, and of course indicates that more of the anesthetic should be given if a deeper anesthesia is desirable. If the pupil is dilated and the corneal or lid reflex is absent the anesthesia is deep, and the further adminis- tration of the anesthetic must be carefully watched, for the danger line has been reached. Even with these conditions present it is sometimes necessary in the administration of ether to increase further the 369 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES depth of anesthesia by adding more of the anesthetic in order to obtain complete relaxation, but in such instances the anesthetist must be thoroughly alert and watch the pulse, respiration, and color most assiduously. When the upper lid is raised quickly the pupil responds to the stimulation of light by contracting during a light or moderate depth of sthesia, but in deep anesthesia it remains dilated. Muscular movements in the surgical stage are usually in complete abeyance, but it is not necessary or even desirable that this depth of anesthesia should always be maintained. It is well to bear in mind that coughing, vomiting, etc.. with, of course, special exceptions, occur during light anesthesia, and that anesthesia should be maintained at such a depth that these phenomena are suppressed whenever their occurrence would interfere with the work of the surgeon. The invariable rule should be that the patient receive as little of the anesthetic as is neces- sary to procure the depth of anesthesia desired for the particular procedure. For some operations the anesthesia may be very light, while for certain others it must be profound. In a general way it may be said that abdominal operations and those upon the genitourinary organs require a deep anesthesia. but even this is subject to exceptions. Some pan particularly alcoholics, require a large amount of the anesthetic to produce the desired state of anesthesia, while others, particularly the debilitated and elderly subjects, and more especially women than men, require only a small amount to produce the same effect. The aim should be not only to administer the min- imum amount of the anesthetic, but also that the rate of administration be continuous and as even as practical, so as to maintain a smooth anesthesia. i. The fourth or toxic stage is not separated from the third or surgical stage by a clear line of demar- cation. However, the general condition of a patient suffering from an overdose of the anesthetic is so different from that of one properly anesthetized that even the onset of the fourth stage is readily recog- nized by the experienced observer. The respiration is shallow, usually increased in frequency under ether, and decreased under chloroform. The pulse is very feeble and rapid, though it may be slow under chloroform. The eyelids separate. The face is "deathly pale" under chloroform, and cyanotic under ether. The nose is cold and cold sweat appears upon the forehead. There is a peculiar expression of the face. The pupils are widely dilated and fixed, and the lid and corneal reflexes are entirely absent. In case ether is the anesthetic the patient is not in so much imminent danger, as when chloroform is used to a toxic degree, for in the former instance the patient usually recovers if the condition is recog- nized, the administration stopped, and appropriate treatment instituted. With chloroform, however, this stage is much more serious, as irreparable dam- age may have been done before the serious condition of the patient is recognized. The IxDrcnox of Anesthesia. Preparation of the Patient. — In all but emergency cases the patient should undergo a preparation before being anes- thetized. Whenever possible the diet should be supervised and regulated, the bowels kept open, and tobacco and alcohol avoided for twenty-four to forty-eight hours immediately preceding a major surgical anesthesia; for a minor anesthesia a less rigid regime should be followed, as far as circum- ill allow. Whenever possible the patient should undergo a rigid physical examination prefer- ably a day or more prior to the anesthetization, special attention being given to the condition of the heart, lungs, kidneys, blood, and to the state of the bowels. Oftentimes an appropriate course of med- ical treatment will improve the patient's condition and fortify it against the shock and depression of the anesthetic and operative procedure. The attending physician will often furnish valuable information o the patient's peculiarities and idiosyncrasies. The ingestion of food and fluids should be regulated so that the stomach is empty at the time of anes- thetization. The bowels should be emptied, but not by drastic means, shortly before the administration, unless there is some special contraindication, while the bladder should be emptied immediately prior to the anesthetization. Children especially are liable to micturition under nitrous oxide unless the bladder is thus emptied. The mouth should be examined in all cases to in- sure the removal of all artificial teeth that are not firmly fixed. Notice should also be made of loose teeth which ruay become dislodged by spasm of the muscles of the jaw, or during the introduction of a mouth wedge or gag. All examinations of the patient just prior to the administration of the anesthetic should be very brief and tactful, as the patient, at this particular time, is highly susceptible to nervous impressions, and consequently much more damage than benefit rnav follow an extended examination at this time. Apparatus, Appliances, and Remedies. — The anes- thetist should, if practical, have his apparatv.- perfect working order before the entrance of the patient, or if the anesthesia is to be induced or main- tained in the patient's room the apparatus should be inspected and placed in order beforehand. The anesthetist should always have conveniently at hand, in addition to the apparatus or applia' for administering the anesthetic, the necessary instru- ments and remedies for the prompt treatment of any accident or compli- cation that may arise at any time during the administration. This in- cludes a mouth wedge, a gag. tongue forceps, mouth prop, a hypodermic syringe, and solutions of adrenalin, or its equivalent, atropine, digitalin, morphine, caffeine, camphor in oil, ergotol, whiskey, a "'breathing tube," oxygen and carbon dioxide in cylinders, and means for perform- ing tracheotomy and pharyngeal or intratracheal insufflation. In using a tongue forceps of the pressure-contact form care must be exercised not to make too much pressure or allow it to be applied too long, as it may cause serious injury to the tongue, consequently a puncturing tongue forceps (Fig. 205) is very useful. Mouth props are used in practically all dental cases. and in all other surgical cases where it is desirable to keep the mouth open for a considerable period of time, or where the gag interferes with the applica- tion of the face mask, especially when nitrous oxide is being used. The '"'breathing tube" is very useful whenever there is respiratory obstruction at the base of the tongue as often occurs under nitrous oxide and less frequently under ether. In suspension of respiration it is also highly useful, as this part of the respir- atory tract can thereby be kept open and a mask applied tightly to the face, and oxygen, or preferably oxygen and carbon dioxide, forced into the lungs, while artificial respiration is simultaneously main- tained. The use of the hypodermic solutions alone should never be depended upon in any serious case, and in emergencies they are of little or no value, but when possible they should be conveniently at hand so as not to delay their prompt administration, when wanted. The hypodermic injection during the administration should be given b}- an assistant, and not by the anesthetist. The apparatus for the administration of anesthetics should be simple in design, construction, and opera- Fta _10. — Clover's Mouth Prop. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, General Surgical ii,,n, ->i as to be easily manipulated under the varying conditions in which it has to be used. No matter how apparently efficient ii may be, a large, cumber- some, and i iplicated apparatus is open to criticism. Ml apparatus and appliances should be kepi thor- oughly cleansed and sterilized, and no apparatus deserves a second consideration thai cannol be easily and thoroughly sterilized. Since the recent intro- duction of rebreathing in the administration of nitrous oxide most of the designers and manufacturers of uratus for such use have lost sight of the fact that rebreathing should cause a change in construc- tion, so that all parts contaminated by the rebreathing be sterilized. Regardless of this fact hundreds of apparatuses for administering nitrous oxide by rebreathing through an integral part of a large and cumbersome stand, not capable of practical sterilization, are being used in this country. Such practice is to be strongly condemned. It is little short of criminal to compel a patient to breathe hark and forth through an apparatus contaminated by the expirations of a previous patient suffering from tuberculosis or other infection. Complete sterilization is indispensible in the rebreathing method. Morphine before Anesthesia. — The use of mor- phine hypodermically as preliminary medication to general anesthetic has been growing in favor, and is now recognized as a good procedure. It has long been noticed that pal ients who suffer from fright and fear preceding the anesthesia or during its induction, suffer greatly from shock, and that out of all pro- portion to the extent of the operative procedure. That, such fright and fear produce distinct patho- logical lesions of the brain cells has been clearly and lusively demonstrated by C'rile. A hypodermic injection of morphine one-half to one hour preceding the anesthesia quiets the patient's nerves, induces a tranquil state of the higher centers of the brain, dispels fear, and creates a pleasant state of mind, thereby preventing or minimizing the shock that usually follows the preanesthetic state. Besides, after this preliminary medication the induction of anesthesia is smoother, quieter, and more rapid, relaxation is more complete, and a lesser amount of the anesthetic is required throughout the entire administration. While this medication alters the size of the pupil, yet there are so many other and more reliable signs in determining the depth of anesthesia that this objection to the use of mor- phine may be disregarded, for its benefits far out- weigh its disadvantages. In prolonged anesthesia under nitrous oxide the use of morphine, combined with either atropine or hyoscine (scopolamine), is practically imperative, as morphine aids materially in securing muscular relaxation, and prevents the inhibitory action of nitrous oxide upon the heart. Moreover, morphine alone should never be used in nitrous oxide anesthesia on account of its depressing effect upon respiration. Administration and Subsequent Treatment. — It is preferable to anesthetize some patients in their own room, others in the regular anesthetizing room, while with nitrous oxide it is often advisable to anesthetize on the table in the operating room, with the patient previously prepared and in proper position. Wher- ever the patient is anesthetized, and whatever anes- thetic is used, the aim should always be to subject the patient to the shortest possible influence of the anesthetic, consequently the administration should never be begun until all the other preparations con- nected with the operative procedure are either com- pleted or will certainly be completed at such a time as not to delay the continuous and expedituous work of the surgeon just as soon as the patient is brought into the proper degree of anesthesia. Any consider- able handling and moving of a patient in the state of surgical anesthesia is to be condemned. Except in the case of nitrous oxide or ethyl chloride the induc- tion should alwaj - be made w ith the patient lying on his back with the head in the body plam and prefer- ably turned a little to one side, the head thereafter being kept iii thai plane if pos ible. With few excep- tions it is dangerous to ke.-p the head of a fully anesthetized patient above the body level. During the administration of an anesthetic it is quite important that the clothing about the patient's chest and neck should be light and loo i ly lilting, the room warm, and the patient's limbs especially protected with blankets. The anesthe- tist should see that the patient's chest is not encum- bered with heavy instruments, and that none of the assistants should lean i hereon. Also t hat the patient's entire body be kept properly covered, and as warm and dry as is compatible w ith the operative procedure at hand, and thai this same care in this respect be exercised until the patient is afterward placed in bed, for undoubtedly much of the unnecessary exposure which one sees in many Operating rooms ami in the handling and transference of anesthetized pa- tients through cold and draughty halls, is a very great factor in the subsequent complications and sequela that occur, and for which the anesthetist or the anesthetic is often held responsible. After the operation is finished and the dressings are applied, the patient's wet clothing should bore- placed by dry, and the patient carefully lifted onto the stretcher or carried to his bed, care being used not to elevate the head. The bed should have been previously warmed by hot-water bottles or by ironing the sheets. The room should be of a temperature of about 06° F., and well ventilated, but with abso- lutely no draughts, and the patient should be kept warm by proper clothing and artificial heat when indicated. The anesthetist should see that the pulse, respiration, and color are satisfactory, and that the reflexes are returning, and when these con- ditions are met his responsibility in the case ordi- narily ceases. The patient's head should be only moderately elevated, unless there are special indica- tions for deviating from this rule. When the cir- culation is poor the foot of the bed should be elevated. The patient should be kept quiet and moved as little as possible, as otherwise vomiting and syncope are more likely to occur. The room should be darkened, and kept quiet and the patient should be encouraged to sleep. All anesthetized patients should be carelully watched until complete conscious- ness returns. The time when water and food may be allowed varies w-ith different anesthetics and with the gas- tric condition of the patient. In general it may be said that they may properly be allowed much sooner after nitrous oxide than after chloroform or ether. If postanesthetic vomiting occurs there should be abstinence from food and water for several hours, excepting that small amounts of very hot water at frequent intervals may be administered to allay nausea and vomiting. A rectal injection of 1,000 to 1,500 c.c of saline solution at the completion of the operation has a tendency to relieve thirst and improve the circulation, and is a good routine procedure after major operations. The Practical Administration op Anesthet- ics. — Nitrous oxide, N,(), is a colorless and prac- tically tasteless gas, and is known either under its chemical name or as "gas," or "laughing gas," on account of its specially pleasant effect upon the emo- tions. Under a low "temperature and high pressure it becomes a liquid, and the nitrous oxide of commerce is in this form, stored in steel cylinders, varying in capacity from twenty-five gallons to several thou- sand gallons. As heat expands liquid nitrous oxide the cylinders containing it should not be exposed to any high temperatures, as an explosion may result, 371 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES although interstate commerce cylinders must be provided with an appropriate safety device which per- mits the gas to escape, before the pressure becomes dangerously high. The gas weighs one ounce to each four gallons, and by knowing the net weight of the cylinder, which is always marked thereon, the amount of gas in each cylinder can be determined quite accurately. This is a very important matter when nitrous oxide is to be used in major anesthesia outside of hospitals where there is no reserve supply at hand. Institutions using large amounts of nitrous oxide find it practical to manufacture their own gas in a private plant, usually located in the basement, store it in gaseous form in a large tank, and pipe it to the operating rooms, ils cost being thereby greatly reduced. Nitrous oxide is administered i n several ways, and as the technique of each is slightly dif- ferent the several methods will be de- scribed in more or less detail. These different methods of administering ni- trous oxide are: (1 ) Nitrous oxide alone; (2) nitrous oxide with air; (3) nitrous oxide with oxygen; (4) nitrous oxide-oxygen, with ether as an adju- vant; (5) nitrous oxide as a prelimi- nary to ether; (C) nitrous oxide-oxy- gen by the intra- tracheal method, and For brief adminis- trations nitrous oxide is remarkably free from danger, being for this purpose much the safest anesthetic known. It also possesses the great advantages of being practically tasteless and odorless, rapid in action, and quickly eliminated, the patient losing and regaining consciousness in very short periods of time with comparative freedom from unpleasant after-effects. While for this form of use it is not essential that there be t lie usual pre- liminary preparation of the patient it is desirable that the stomach be at least comparatively empty, and in children and nervous folk the bladder should be empty. Usually t he patient is able to arise and walk in a very few minutes after such adminisl rat ions. For the prolonged administration of nitrous oxide there should he the same preliminary preparations of the patient as with the other anesthetics, and while consciousness returns very quickly after this anesthetic is withdrawn yet the patient should not be permitted to make any undue exertion for the first hour after a major anesthesia. The Apparatus. — The apparatus for administering nitrous oxide is of necessity more complicated than that for the other anesthetics. However, experience has shown that the large, heavy, and cumbersome apparatus is not only not necessary, but a distinct disadvantage, for in the light of present day science the principles underlying the administration of the different anesthetics are so similar that one apparatus may advantageously be used for all anesthetics and for all methods except those highly specialized. The Coburn apparatus, devised by the author, Fig. 211. —Hewitt's Nitrous < >\i.k' Oxygen Inhaler. and herewith illustrated, is based primarily upon the principle of simplicity. While for administering nitrous oxide a special stand is not necessary for holding the cylinder or cylinders, such a stand is however, highly desirable, convenient, and useful' The stand should furnish means for holding at least two cylinders, so that when one cylinder is exhausted a fresh supply is at hand and ready for instant use without delay. The stand should also provide means for holding two cylinders of oxygen. Instead of one of the other cylinders mentioned a cj'linder of CO, gas or of a mixture of CO., gas and oxygen may be attached. Certainly such C3 r linders should always be in the operating room at least, ready for immediate use at any time. The hospital stand (Fig. 212) carries four cylinders, and is constructed so that means may be added for holding two additional cylinders. It matters not in what order or position the different cylinders are attached .-is they all. both singly and conjointly, communicate with the tubing that leads to the rubber bag. The stand is strong, and will support the medium sized cylinders. It is mounted upon wheels Fig. 212. — Coburn Apparatus Complete, with Hospital Stand, for Adniinistei itijr ami Warming Nitrous < >xide-oxygen aud Ether by the Rebreathing Method. and may readily be moved about the operating room or from one room to another with the cylinders attached. In the center it carries two shelves on which may be kept all the paraphernalia of the anes- thetist and the inhaler when not in use. It serves, therefore, as a combined anesthetist and cylinder stand. The portable stand (Fig. 213) is of light construction and so arranged that it may be very easily and quickly assembled or taken apart and folded into a small space, thus rendering it readily portable. It is mounted on castors and supports four cylinders, 372 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aiirsthc^i.i, General Surgical which either singly or in combination communicate with the rubber tubing that leads to the rubber stop- cock attached to the rebreathing bag Fig. 213.- Apparatua w nil Folding, Portable Stand. The neck of the bag is attached to a metal fitting which carries a shut-off and air-vent operated together; when the ether attachment is not used this fitting is attached directly to the inhaler. The inhaler carries an inner tube in which are located two light and delicately acting valves, so arranged that one prevents breathing back into the bag when the exhalations are to escape, while the other prevents air being inspired through the expiratory orifice during inspira- tion. When there is to be rebreathing the valves are both thrown out of action and the expiratory orifice is closed by turning the little knob (rebreathing control) through an angle of 90°. To the inhaler is attached a face mask (made either of transparent celluloid or of metal) which carries an inflatable rubber hood. The ether attachment consists of a chamber for holding the gauze and a cup for holding the ether, the bag carrier fitting into one end of the chamber and the inhaler into the other. The opening at the end of the chamber into which the bag carrier slips is quite large, and through this opening the necessary gauze is easily and quickly placed within the chamber. As the chamber is ample in size it is never packed, but just loosely filled with coarse gauze. The cup is attached to the chamber and may always be maintained in an upright position by turning the chamber on its connection with the inhaler. At the top of the cup is a needle-point valve for controlling the flow of the ether upon the gauze in t he chamber. As the ether drops from the cup upon this gauze it can be plainly seen, and the rate of administration can thus be accurately regulated at all times. The rubber bag and the ether attachment extend either back over the patient's head or down over the chest. A small and light electric heater (] ig, 215), which may lie connected to any lamp socket, either diri I or alternating current, i- attached to the chamber by spring clamps whenever it is desired to warm the vapor. A small rheostat i- provided to control the radiation. This heater may l>e attached or detached at any time without interrupting the administration of the anesthetic, and it thoroughly warms all the vapor to body temperature at the time it is inhale, I, Systems of Administering Nitrous Oxide.— 'There are two systems of administering nitrous oxide: (1) Without rebreathing; (2) with rebreathing. 1. In the first system the exhalations all pass out into the air, and the patient continuously in- spires fresh nitrous oxide either with or without other additions (air, oxygen, or ether); this is its nei-i e .p. nsive I or ui of admin ist rat ton, as the patient's respiratory movement, under nitrous oxide averages "Joll gallons per hour. _'. In tin- system of rebreathing there are two fundamentally different principles: (a) When the supply of nitrous oxide is a con- tinuous flow only a part of each expiration passes back into the bag and is reinhaled, the other part escapes from the inhaler into the air. .Most of the apparatuses for this form of administration re- quire the patient to rebreathe through a long tube. This tube presents a two-fold disadvantage: (1) it requires energy to breathe back and forth for a length of time through a long tube; at the same time _') it causes an unnecessarily high retention of carbon dioxide, inasmuch as one expiration does not reach the bag before the next inspiration takes place, and this inspiration, therefore, consists almost entirely of a mixture of the previous expiration and the con- tent s of the face mask and tube only; consequently the patient continually inspires a higher percentage of carbon dioxide than would be the ease were the bag placed close to the patient's face. This method of con- tinuous supply and rebreathing through a long tube requires about 125 gallons of nitrous oxide per hour. (6) When the supply of nitrous oxide is inter- mittent, the patient breathes back and forth into "EE-DLE y*l.VE f ■ ■ n r Respcath^ Inhaler \ RcarTEATHtNa CONTROL \ Fig. 214. — Coburn Apparatus for Administering Ether and Ethyl Chloride by the Rebreathing method, Stand Disconnected. the bag from one to eight minutes, by which time the bag is emptied, usually by the exhalations escap- ing from the inhaler instead of passing back into the bag. The bag is then refilled and the patient again rebreathes the bag of gas the desired length of time. 373 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The method of intermittent supply and rebreathing requires an average of about thirty gallons of nitrous oxide per hour, and is therefore much the most econom- ical method of administration. Besides it is the more scientific, as the stimulant action of carbon dioxide on respiration is needed to counter-balance the depressing respiratory action of nitrous oxide, as well as to pre- vent shock. And in the method of intermittent supply of nitrous oxide the amount of rebreathing, and conse- quently the carbon dioxide retention as well, is under much better and more positive control. Fig. 215. — Coburn Apparatus for Administering and Warming all Liquid Anesthetics by the Open Drop Method. Rebreathing nitrous oxide undoubtedly renders its administration, whether short or prolonged, much safer, and at the same time the resulting anesthesia is deeper, smoother, and better in every particular. Pure Nitrous Oxide and Nitrous Oxide with Air. — In addition to the apparatus and gas the anesthetist should also be provided with at least a mouth wedge, props, tongue forceps, a gag, and, if possible, the other accessories previously mentioned. In dental work the mouth prop should be placed in position before the administration begins. All such props should have a ligature attached so that they may not be swallowed should they become displaced. For short anesthesias — the only form of administra- tion for which nitrous oxide alone, or combined with air is adapted — the patient may be placed in any posi- tion required by the operator, except in grave car- diac cases, but usually a semirecumbent posture gives sufficient elevation of the head. It is important that the respiratory movements and the air-passages be unobstructed at all times. The rubber cushion should be well inflated, the bag nearly filled with gas, with the air-vent open and shut-off closed. With the expiratory orifice open the inhaler is next placed over the patient's face, care being exercised to see that the mask and inflated cushion form an air-tight fitting with the patient's face. The patient is allowed to make a few respirations in order to get accustomed to the apparatus and to learn that it need cause no appre- hension. Air is being inspired through the air-vent, and the expirations escape at the expiratory orifice. After thus breathing a few times, the air-vent is closed. The patient now inspires nitrous oxide from the bag and all the exhalations escape at the expi- ratory orifice. After making four or five such exhala- tions, so that the air in the apparatus and respira- tory tract may be replaced with nitrous oxide, the expiratory orifice is closed, and the patient now re- breathes nitrous oxide back and forth from and into the rubber bag. During all this procedure the room should be kept quiet. The induction of anesthesia with nitrous oxide is usually so rapid that it is impossible to divide it into all the different stages. The first effect usually dis- cernible is a change in the patient's color; at first it is a little dusky, grows darker, and finally becomes markedly cyanotic, the breathing becomes loud and stertorous, and jactitations or irregular muscular contractions rapidly follow, unless the administra- tion is stopped or air (or its equivalent) admitted. The administration should not be pushed to the point of causing jactitation, so whenever there is marked cyanosis or stertor the anesthetic should be discon- tinued, or the air-vent opened for one or two inha- lations of air (the shut-off operated simultaneously automatically prevents the waste of the nitrous oxide). The administration may be continued by allowing the patient to inspire a breath of air about e five respirations. A bag full of nitrous oxide may thus be rebreathed for from three to five minutes. The time required to produce anesthesia varies from a few seconds to a few minutes, the average being a little less than one minute. The administration of nitrous oxide pure and com- bined with air should be confined to dental and other very brief operations when a complete anes- thesia is not required. In some cases, especially for dental work, it is desirable to administer nitrous oxide so that at the same time the oral cavity may be open and unob- structed for operations therein. For this purpose a nasal inhaler is used and the gas is forced into the nasal passages under pressure. It is absolutely essential that such an inhaler make an air-tight fitting over the patient's nose, and that a net be placed over the rubber bag to prevent its excessive expansion under the pressure necessary to force nitrous oxide through the patient's nasal passages. If a Macintosh bag is used the net is not needed. The patient is anesthetized in the same manner as with the face inhaler except there is no rebreathing and the mouth is kept covered with a small sheet of rubber. "When the patient is anesthetized the ex- piratory orifice is closed, and nitrous oxide is forced through the nasal passages, while the mouth is open during the performance of the operation. Although the patient necessarily inspires considerable air through the mouth, it is advisable to administer simultaneously a small amount of oxygen when in- dicated by the patient's color. The state of analgesia in which there is loss of setts sation of pain but not loss of consciousness, and which is now very much used in dentistry, is secured by administering a somewhat smaller amount of the anesthetic than is necessary for anesthesia. In this form of administration for dental purposes the nasal inhaler is used, and as the mouth is open, more or less air is inspired through it, consequently very little additional oxygen is required in prolonged adminis- trations. Analgesia might be termed "anesthetic intoxication." Nitrous Oxide with Oxygen. — The administration is begun the same as that of nitrous oxide pure, but at soon as the patient shows the first tinge of cyano- sis, pure oxygen, in a small amount, is added from a cylinder to the rebreathing bag. The anesthetist soon learns to gauge the amount of oxygen needed, being cautious not to add too much, as more can be added at any time if the color indicates that the oxygena- tion is deficient. It is entirely unnecessary to know the percentage of oxygen used; sufficient oxygen should be added to maintain a normal oxygenation, 374 RKFEHEXCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, General Surgical and as the patient's color is the most, delicate indi- ator no other guide is needed. After the patient has rebreathed a bag of gas from two to eighl minutes the expiratory orifice is opened, and the bag is automatically emptied by the exhala- tions passing out into the air. Just before the bag is mletely empty the expiratory orifice is closed, the bag is nearly refilled with nitrous oxide, and the indicated amount of oxygen added, or, if the patient lightly cyanotic, the oxygen maybe added Brst. thus rebreathing a bag of gas and oxygen for a few s, emptying and refilling in turn, as outlined, this form of anesthesia may be maintained as long as desired. Care and skill, however, must be exercised to maintain, as nearly as possible, a normal color of I he pa- 1 s cutaneous circulation, for a continued cyanosis throws considerable extra strain upon the heart. On the other hand, too much oxygen should not be i, as it lightens the anesthesia. It requires a little aptitude and experience to administer this anesthetic throughout a prolonged operation and io pilot the patient successfully through the narrow mnel that lies between a too light and a too deep anesthesia. The best guide in maintaining the proper depth of anesthesia is the respiration and the respiratory sounds. The amount of rebreathing is to be governed by depth of anesthesia and the effects of the retained carbon dioxide. As a considerable amount of the nitrous oxide is absorbed by the blood the anesthesia may become too light on account of the diminished strength of the gas in the bag, so that it is not advisable to rebreathe the maximum period. The effects of the retained carbon dioxide upon respiration are very noticeable. As has been shown by Henderson, the respiratory center is controlled by the amount of carbon dioxide in the blood. When the carbon dioxide is increased (the threshold of the respiratory center remaining the same) pulmonary ventilation is increased, i.e. respiration is stimulated in frequency, or depth, or both. When the carbon dioxide in the blood is low, respiration is depressed and the venous system loses its tonicity. When the veins dilate less blood reaches the heart, and there- fore less blood is pumped on through the circulatory system, consequently shock supervenes. As nitrous oxide primarily stimulates, and finally depresses respiration, there is a special indication for its administration by rebreathing, so as to secure the direct stimulant action of carbon dioxide upon the respiratory center. Besides, the increased rate and depth of respiration permit of the absorption of a larger amount of nitrous oxide, and rebreathing therefore deepens the anesthesia. Under ordinary conditions an eight-liter bag of gas can be rebreathed for an average of about three minutes. A condition of excessive carbon dioxide retention is shown chiefly by deep and labored res- piration. Increased blood pressure and decreased frequency of cardiac action also indicate too high a retention of carbon dioxide. Pulmonary ventilation, however, is not the only source of excessive loss of carbon dioxide, for, being a diffusible gas, it readily transpires through the thin capillary walls whenever there is a considerable exposure of these vessels. In abdominal operations, with the viscera exposed, there is such a pronounced loss of carbon dioxide from this source that a patient will tolerate to good advantage double the amount of rebreathing that the same patient will tolerate in the same anesthesia when the abdomen is closed, or in an operation where there is little exposure of the capillaries. Accordingly, in abdominal operations, and kindred conditions, a patient can advantageously rebreathe an eight-liter bag of gas from four to eight minutes. As nitrous oxide causes more or less swelling of the tongue, there is considerable trouble in this anes- thesia from the tongue obstructing respiration. Aa one hand is required to hold the mask tightly against the patient's face, and the other is occupied with supplying the requisite ease . etc., there is little opportunity for holding the .jaw forward. To meet this situation I devised the breathing tube'' iiig. 204) previously described. It can be inserted the mask reapplied so quickly, that the patient makes no n very during its introduction, from even this evanescent, anesthetic. The advantages of nitrous oxide-oxygen anes- thesia are: It is pleasant for the patient, causes little or no depression (or shock), and is followed by little or no depression or vomiting; it causes no irritation of the respiratory or genitourinary tract and does not impair the- patient's resistance against infect ion. [ts disadvantages are: The anesthesia and relaxa- tion are not always complete; it requires a special apparatus and rather burdensome supplies for its administration, and the cost, of the nitrous oxide is more than that of the other anesthetics (about SI. 00 per hour with the method just described, or sixty-five cents with hospital discounts). Nitrous Oxide-oxygen with Bther as an Adjuvant. — This administration is conducted the same as that of nitrous oxide-oxygen (just described) except that when the anesthesia is too light or the relaxation incomplete a small amount of ether vapor is added to the nitrous oxide by slightly turning the needle- point valve on top of the anesthetic cup, and the ether drops slowly upon the gauze in the chamber, and is immediately vaporized. And with the respirations deep and rapid under the stimulating influence of the carbon dioxide in the rebreathing method it only requires a small amount of the addi- tional ether vapor to obtain a deep anesthesia with relaxation in all cases. In order that the ether may drop regularly it is necessary that the bag never be distended, for otherwise the pressure prevents the ether from dropping upon the gauze. It is also necessary that the cap does not completely close the opening on the top of the cup, for without a little air-supply a vacuum is created in the cup, and this prevents the ether from dropping into the chamber. Inasmuch as the ether may be added continuously, or pure ether administered by either the open or closed methods until the desired depth of anesthesia and degree of relaxation are secured, this method of administration is dependable and is adapted equally well for major as for minor surgery. The aim in this form of administration should be to use the minimum amount of ether, and have the major part of the anesthesia produced by nitrous oxide, so as to avoid, as far as possible, the depress- ing, nauseating, irritating, degenerating, shock- producing, and immunity-destroying effects of the former anesthetic. And the fact, which is not usually recognized, is to be strongly emphasized that the ether thus used does not produce the same propor- tion of its toxic effects that this amount bears to the amount necessary to maintain anesthesia with straight ether. It is the last third, and not the first two- thirds, of straight ether that produces almost all of its toxic effects. In other words, after a certain effect is produced by the administration of straight ether the additional amount necessary produces toxic effect out of all proportion that this additional amount bears to the total amount used, and it is this fact that explains the comparative absence of the toxic effects of the ether used as an adjuvant to the nitrous oxide, as outlined. When hyoscine (scopolamine) has been combined in the preliminary hypodermic injection with mor- phine, considerably less ether will be needed as an adjuvant, and in a smaller percentage of cases, than when atropine has been combined with the morphine. Whenever hyoscine is used it is necessary to keep the 375 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES blood extra well oxygenated, especially until the stimulant action of carbon dioxide upon respiration is secured. Nitrous Oxide as a Preliminary to Ether. — This administration is begun the same as that of nitrous oxide alone (q.r.). The average patient, after re- breathing the nitrous oxide for twenty to forty seconds, shows the signs of anesthesia, and at this time, but not until there are signs of anesthesia observable, the valve on top of the cup is slightly turned, and ether thus slowly dropped upon the gauze. The ether should be gradu- ally increased but not more rapidly than the patient's tolerance of the irritating vapor will permit with- out disturbance. Marked cyanosis should be pre- vented by opening the air-vent and allowing the pa- tient to inspire one or two breaths of air every five or six inspirations, or by leaving tlie air- vent slightly open during the re- mainder of the in- duction period. (A much better method is to add pure oxygen direct to the rebreathing bag and thereby prevent all cyano- sis.) It is impor- tant that, the drop- ping of the ether should not be begun until the patient is unconscious from the nitrous oxide, and that it should be added very slowly at first, for if the vapor is too strong the patient will either hold his breath or cough. But if no coughing occurs and the patient breathes deeply and regularly the ether may be in- creased quite rapidly. Smokers are quite liable to cough with even a mild vapor, so with this class it is necessary to proceed with the ether administration very slowly. Alcoholics are very susceptible to the oxygen deprivation of nitrous oxide and so require a large amount of air (or of pure oxygen). Only a few patients will require more than one bagful of nitrous oxide. The rebreathing bag should be used until the patient is relaxed, when it may be removed, and the administration of ether continued by the open method, if desired. " Nitrous oxide should not be administered imme- diately before the administration of chloroform, but if chloroform is to be the anesthetic, and there is no respiratory irritation, the induction may be made with nitrous oxide-ether as above outlined and the change made to chloroform just as soon as the pa- tient is anesthetized witli the ether sequence. Ethyl Chloride. — While ethyl chloride was em- ployed about sixty years ago to produce general anes- thesia it was not until within the last decade that its use has met with any general public favor. Many of the fatalities following its use have been attributed to impurities which, to-day, are not found in the product intended for inhalation use. It is supplied in con- tainers of 60 to 100 c.e. capacity and in glass ampoules of 3 and 5 c.c. The latter are to be broken and used at once, while the former has a valve which controls its Fig. 216.— Hewitt's ( with Clover's Etl as-ether Inhaler er Chamber. administration, which is usually in the form of a spray. Ethyl chloride for inhalation differs from that intended for local anesthesia as marketed by some manufac- turers, so one should always be sure that the prepara- tion for general anesthesia is used. Pure ethyl chlo- ride is the only form that is adapted for inhalation. Ethyl chloride may be administered by either the open or closed systems, and, as is the case with ether, the skilled and qualified anesthetist usually prefers the closed method. Like nitrous oxide it is rapid in action, and the anesthesia is likewise evanescent. If the administration is for a dental operation a prop should always be previ- ously inserted, and the patient may be in a semi- recumbent position. In the open method any suitable mask such as the Schimmelbusch or Yank- auer's may be covered with ten or twelve layers of gauze and used. The Co- burn apparatus, with the bag removed, offers dis- tinct advantages in this Fig. 217. — Schimnielbusch's Folding Mask. form of administration, inasmuch as the gauze in it is several inches distant from the patient's face, and conse- quently the vapor is always well diluted with air before being inhaled. And, besides, the exhalations do not pass over the gauze and needlessly waste about half of the anesthetic. Whatever apparatus or mask is used the ethyl chloride is slowly sprayed upon the gauze, but if the usual open mask is used care must be exercised not to spray the anesthetic suddenly, or in a large amount, or with much force. Respiration is stimulated in frequency and increased in volume, and the patient's color should be quite florid. Anesthesia is induced so quickly that the different stages are u -i tally not distinguishable, as it ordinarily requires only about a minute for the induction period, and a few c.c. of the anesthetic. If a prolonged anesthesia is desired, the anesthetic is sprayed in small quanti- ties at frequent intervals upon the gauze, extremely diligent care being exercised in watching the eye reflexes, the pulse, blood pressure, and, of course, the breathing, for signs of overdosage. As ethyl chloride produces a fall in blood-pressure it is not well adapted for prolonged administration, and its after-effects are more unpleasant than those of nitrous oxide. In the closed method of administering ethyl chloride a special apparatus is necessary and for this purpose numerous ones have been devised. The kauer's Mask. Coburn apparatus, with the bag attached, is well adapted for this purpose. The bag is partly filled with the patient's expirations and the anesthetic sprayed in small quantities at frequent intervals into the bag through a slight opening of the air vent. It only requires about forty or fifty seconds of time and from 3 to 5 c.c. of ethyl chloride to induce anes- thesia by this method. The anesthesia is recognized by 376 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, General Burglcal its usual signs but more especially by the snoring char- acter of respiration. Many anesthetists -pray from ;; to 5 c.c. of ethyl chloride into the bag at once, but I believe it to be dangerous practice to introduce such large amounts at one time. Prolonged anes- thesia is maintained by spraying the anesthetic into the bag al frequent intervals, extreme care be- ing taken to watch for the signs of overdosage. When ethyl chloride i- used as a preliminary to ether tin- Coburn apparatus can be very advanta- f;-lv used in either the open or closed methods. administration is begun a mtlined, es that the cup should be previously filled with ether .lust as soon as the palie.it exhibits signs of at thesis the valve on the cup is slightly turned, and thi ether is slowly dropped upon the gauze, the rate oi the ether administration being cautiously and gradu- ally increased by turning the needle-point valve. In the open method it i> advisable to spray a little ptlivl chloride upon the gauze after the admini tion of ether is begun so as to prevent any recovery, but in the closed method this will rarely be necessary. Ethyl chloride possesses no particular advantages over nitrous oxide except that of convenience; it is inctly more dangi rous and its use is followed by more disagreeable after-effects, .such as headache. vomiting, dizziness, etc In general, it may be said that ethyl chloride is better adapted for administra- tion to i hildren than to adults. Ethyl bromide is administered in practically the manner and amounts as ethyl chloride except that it is dropped upon the gauze or poured into the bag or inhaler instead of being sprayed. In the trn apparatus -4 to S c.e. are poured into the cup and it is then dropped upon the gauze by turning the needle valve. If there is to be an ether sequence, just as soon as the patient is anesthetized ether is poured into the cup and the administration of this anesthetic begun, so there is no recovery from the preliminary agent. Ethyl bromide seems to possess no special advan- over ethyl chloride, and is much more liable to decomposition. Ether. — Ether is administered by one of four general systems: (1) The open; (2) the closed; (3) rectal etherization; (4) intravenous etherization; and various modifications of these systems, including the intratracheal method, in conjunction with pure oxygen, warmed vapor, etc. Hewitt makes a different classification, including the semi-open system, which he defines as '•limiting to some extent the access of atmospheric air without in any way retaining the expiratory products for rebreathing." This definition, however, describes an impossible condition, for the air supply cannot possibly be limited unless the expiration is rebreathed. Limiting the air supply, in the administration of ether, does not decrease the respiratory volume, hence, in a general way, there must always be re- breathing in the proportion that the air supply is restricted (excepting, of course, where there is an artificial supply of some gas, such as nitrous oxide or oxygen, that is simultaneously respired, and whose volume is equal to that of the restricted air). The semi-open system, or as it is sometimes called, the semi-closed system, then, is simply a modification of the closed system. The intratracheal method, on the other hand, appears to be simply a modification of the open system, inasmuch as there is no rebreathing and the air supply is abundant. The induction of anesthesia with ether requires several minutes, and is more or less disagreeable to the patient, inasmuch as the odor of the vapor is unpleasant and produces more or less of a choking sensation. Besides, there is a very general fear and dread of undergoing the ordeal of a general anesthesia, hence at the time of administration the patient's nerves are in a state of exa ed excitation which causes a prolongation of the induction period and ised resistance ami struggling. Tin- fright fear, and the struggling, especially with ether by the method, all tend to produce rapid breathing, which in turn causes shock. The acapnia thus produced by etherization may In i to primary heart failure, even in normal subjects, according to Henderson. 1" Cril ha down thai tear and fright produce distinct pathological lesii >ns of t he brain cells. Mi.', two tnvi have demonstrated the scientific basis fur the a lute need of a rapid and pleasant induction of ane — the ia and the elimination "i preanesthetic fear. Anesthesia cannot be in. lined rapidly, as that term is here intended, with straight ether, and such an induction is usually distinctly unpleasant, hi there is a scientific, as well as esthetic basis, for the plea-ant induction of anesthesia with rapidly act- ing anesthetizing a^'-uts such a- nitro ■ ■ and ethyl chloride, followed by an ether sequence when- ever the latter anesthetic is t.i be administered, the methods having already been described. The pre- anestl c is best prevented by the administra- tion of morphine, as outlined by (.file. Besides, when morphine is used less of the inhalation anes- thetic is required, and morphine in proper dosage is less toxic than ether. Ether vapor is highly inflammable and therefore it should never be administered near an open flame. In the use of the Paquelin cautery this physical property must always be borne in mind by the anesthetist, as well as by the surgeon. The open system of administering ether requires only a very simple inhaler, preferably a Yankauer's mask, but any chloroform mask will answer very well. In the selection of face masks preference should be given to those that fit the contour of the face so that ail the air that the patient breathes is inspired through the gauze. Accordingly, the masks that have a pliable rim that can be formed to fit the con- tour of individual faces are useful. The mask should be made of metal and simple in design and construc- tion so as to be easily sterilized by boiling. Such a mask should be covered with ten or twelve layer- of gauze. The perfection of the open system is attained in the open drop method, and it is this method that will be outlined. If the anesthesia is to be induced with ether the gauze-covered mask is placed gently over the patient's face in proper position and the patient permitted to breathe for a few seconds through the mask and learn that it offers no obstruction to respiration. The highly esthetic anesthetist next adds a few drops of some pleasant perfume. The administration of the ether is begun by dropping the ether very slowly a single drop at a time upon the gauze, and very gradually increasing the rate of administration as the patient becomes accustomed to the vapor. The frequency of the drops and the rate of increase will depend largely upon the regularity of respiration and laryngeal irritation. If the patient holds his breath or coughs, the vapor is too strong and the ether must be dropped more slowly. Mus- cular subjects, and more especially alcoholics, will sometimes struggle violently, but forcible restraint should be used only when necessary. The mistake is much more frequently made of administering the ether too rapidly during the induction rather than too deliberately. It is not the amount of ether that is dropped upon the mask that produces or maintains anesthesia, but the amount that the patient inhales and absorbs, consequently the rhythm and depth of respiration are important guides in determining the rate of administration in the induction as well as in the maintenance of anesthesia. The idea cannot be too strongly emphasized that in the open drop method the ether should be dropped regularly and 377 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 219. — Allis' Ether Inhaler. continuously, and not poured upon the gauze in quantities at intervals, as is so often done. Muscular subjects, and more especially alcoholics, are often quite difficult to relax under ether by this method, so that it becomes necessary to use some rebreathing. This may be secured by covering the gauze with a small sheet of rubber in the center of which is a hole about five-eighths of an inch in diameter and through this hole the ether is still dropped upon the gauze. If an impervious covering is not available several more sheets of gauze or a towel may be placed on the mask so as to limit the air supply and thereby cause rebreathing. After the patient is relaxed only the original gauze need cover the mask. Surgical anesthesia is recognized by the absence of the lid re- flex, moderate dilatation of the pupil, and muscular relaxation. Whether surgical anes- thesia is induced with straight ether, or by a preliminary anesthetic with an ether sequence, the anesthesia is further maintained by a regular and constant dropping of l he ether upon the gauze. < hi account of the diffi- culty of continuously hold- ing the ether can in the hand and continuing a reg- ular and constant drop- ping of the anesthetic, especially throughout a pro- longed operation, the Coburn apparatus is very useful for this form of administration, inasmuch as the ether is added by a mechanical drop method, and therefore the drops are mechanically regular and constant. Since the air supply in this apparatus, when the bag is removed, is free and no rebreathing takes place it completely fulfils the requirements of the open drop method. Besides, in this apparatus the expirations do not pass over the gauze and thus waste the anesthetic and thereby saturate the operating room with ether vapor. As ether stimulates respiration, its administration by the open method causes more or less acapnia, and consequently more or less shock supervenes. Periods of apnea from a few to many seconds in duration are frequently seen during this form of administration, and these are undoubtedly due to the acapnia which the open method of administration tends to produce. It has long been recognized by skilled anesthetists that less shock follows the administration of ether by the closed method than by the open method, and the work of Henderson gives scientific vertification of this clinical observation. The acapnia of the open method may be overcome by the simultaneous administration of carbon dioxide gas, either pure or mixed with oxygen, for when there is a pronounced indication for carbon dioxide admin- istration oxygen is usually indicated also. A mixture of ten per cent, carbon dioxide and ninety per cent, oxygen is a very good proportion to use and either such a mixture, or the carbon dioxide and oxygen in separate tanks, should be convenient at hand in every well-appointed operating room, for use not only in emergencies, but also when shock is either probable or developing. The old adage that "an ounce <>f prevention is worth a pound of cure" is strikingly verified in all general anesthesia work, and as this science is developed it becomes more and more apparent that the anesthetist must be a person keen in perception, discriminating in judgment, and most attentive to detail. For years there has been such ceaseless agitation regarding the desirability of administering ether drop by drop in the open method that sight has been lost of the other and even more important duties of the anesthetist. Almost any one can be taught to drop ether; it is easy to take the pulse, and to count the respiration, and it requires little instruction to record the blood pressure accu- rately. But these are not all that must be observed, for as Henderson well shows it is the volume of the blood actually pumped onward, that, in the proper protection of the patient's vital interests, surpasses all else in importance, for in the development of shock the arterial blood pressure is high and the pulse and respiration are good. The evaporation of ether upon the gauze in the open method produces quite a cold vapor, on account of the large quantity of ether used. In a series of observations I found that in a moderate anesthesia the temperature of the inspired vapor was 45° F., in a deep anesthesia 3.5° F., and in a profound anesthesia 32° F., the operating room temperature being 75° F.; and in these temperature observations I have been corroborated by Joss, who conducted a perfectly independent investigation of this phase of the matter. Vapors, as a rule, are more irritating cold than warm, and this is especially true of ether, conse- quently it has long been held that the cold vapor of ether was, per se, a factor in the production of post- operative lung complications. This general belief is probably correct, although it is conceded that in pass- ing through the upper respiratory tract it is probably warmed to body temperature by the time it reaches the lungs. It is also certain that the heat necessary to warm this cold vapor to body temperature is ab- stracted directly from the patient's vitality. In prolonged anesthesia with ether by the open method, the energy thus abstracted from the patient is not infinitesimal in amount by any manner of means, and in a number of such cases, it must be borne in mind, there is urgent need for the utmost possible conserva- tion of vitality, so the needless loss from this source should not be longer disregarded. Davis says: "The effect of warming ether vapor before inhalation is very marked. In twenty-six patients anesthetized by this method the loss of temperature averaged 0.29° F., against a loss of 1.02° F. in 140 cases under similar operating-room condi- tions by the open drop method." This shows a difference of 0.73° F. in loss of body temperature in favor of the warm ether vapor over that of the cold. This double loss of heat, however, is not the only detrimental effect of cold ether vapor, for as Joss well says, the cooler air chills the air passages, undoubt- edly lowering their resisting powers and checking the movements of the cilia of the epithelium lining them. The ciliary movement is affected by variation of tem- perature and is entirely arrested at the freezing-point. Infectious material is thus liable to find its way more readily into the finer air passages as salivation becomes increased under the influence of the anesthetic. In order to avoid the effects of the cold vapor, when either is administered by the open method, I devised the electric heater previously described, and when this is attached to the chamber it warms the vapor to body temperature at the time it is in- haled. And as I have elsewhere stated that "while it would require very extended clinical experience to establish any reliable statistics on the difference in postoperative complications it can be said with a certainty that when the warm vapor is used the respirations are quieter and smoother, and the secre- tion of mucus less — facts strongly indicative of less trauma to the respiratory passages. And this is all the more significant when it is recalled that pneumo- cocci and other pathogenic organisms are practically ever present in the respiratory tract, and that ether, through its action on the phagocytes, materially weakens the patient's natural defenses against in- 378 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Am . Mll ,. ,.,„,,,, nurKical feotion in general, as well as thai against pneumo- cocci in part icular." / ■/.,. [dm n ration of Ether by the Closed S H is doubtful who firs) discovered theadvantai Limiting the air supply in the administrat ion of ether. Clover, in 1876, described "An Apparatus for Ad- ministering Nitrous Oxide Gas and Ether Singly or Combined. And a few months later he described y s "Portable Regulating Ether Inhaler." In L877 Ormsby brought his inhaler to the attention of the profession. While neither of these inhalers is in use iv extent in the United States modifications of the two types of inhalers are used, so a brief descrip- of them and more particularly of their differences, will here be given. the Clover and the Ormsby inhaler have a fare mask and a rubber rebreathing bag, and be- tween the lias; and mask is the ether supply for vapori- zation. The original Clover inhaler has no special provisions for air supply while such provision is B/..2& FlG. 220. — Clover's Self-regulating Kther Inhaler and Case. made in the Ormsby inhaler. The difference in supplying the ether vapor is quite radical, and it is to this difference that special attention will here be given. In the Clover inhaler a part of the patient's inspirations and expirations pass back and forth over liquid ether, thus producing a vapor practically uniform in strength, while in the Ormsby inhaler the ether is poured on a sponge in quantities at intervals. producing at one time a strong vapor and at another time a weak vapor. Practically all of the inhalers in the United States that are specially designed for the administration of ether by the closed method embody the Ormsby method of supplying the ether after the patient has been anesthetized. To the author it seems a significant fact that in England, where the Clover principle of supplying a uniform vapor predominates, the closed method is in very extensive use, while in the United States, where, after the patient is anesthetized, the Ormsby prin- ciple of supplying a vapor varying greatly in strength at different intervals, has been practically the only closed method used, the closed method is not so popular. Besides, it is this feature of the intermittent and irregular supply of ether by the closed method that has been assailed by so many writers on the subject, including the Anesthesia Commission of the American Medical Association. The concentrated vapor that occurs at intervals produces pronounced and unnecessary irritation of the respiratory passages as evidenced by the increased secretion of mucus and injury to the epithelial cells. Inasmuch as less ether is required by the closed method than by the open method, there should be less irritation, and this is the ease when the vapor of the closed method is constant and regular. Besides, the vapor is warmer, since the warmth of the expirations elevates its temperature. The other chief objection to the closed method is the retention of carbon dioxide, but, as Henderson has so clearly and conclusively shown, the carbon dioxide, properly regulated, is a distinct benefit and not a detriment. An inexpi n tve inhaler is always available, a- i can be made from a paper-COne and a folded tov.el or gauze, ami while this is crude it is quite efficient. [n inducing anesthesia with such an inhaler, three or four drams of ether are pom,-. I upon the absorbent material, which should be of coarse composition, and the cone slowly placed In position over the patient's face, allowing the patient's respirator} pa ages to get accustomed to and anesthetized bj the vapor before placing the cone tightly over the face. Holding the breath, coughing, or laryngeal or other spasm indicates that the- vapor is too strong, o the inhaler should be removed, the patient allowed a little air, and the inhaler then held SO that a more attenuated vapor is inspired until the anesthesia deepen-, when a stronger will be tolerated. More ether is added in small quantities as indicated. In inducing anesthesia with ether by the clo method with the author's apparatus, the bag is first. partly distended with the patient's expirations, and then the administration of ether is begun very slowly by slightly turning the valve on the cup, and as tin; ei her drops upon the gauze it can be plainly seen and the rate of administration can be very accurately gauged. As the patient's air-passages become accus- 1 to the vapor the drops are to be increased in frequency. Holding the breath, coughing, or spasm of any of the respiratory muscles indicates that the vapor is too strong, and the valve should be turned back a little so the drops will be slower; then, as the patient's breathing becomes regular, the rate of the drop is gradually increased by slightly turning the needle-point valve. When signs of cyanosis appear the air vent should be slightly opened, so that a little air is inspired with each inspiration, or a little pure oxygen may be added to the rebreathing bag. If the latter method is used for furnishing the requisite oxygen there is a retention of a larger amount of earl 'on dioxide, and respiration is quickened and deepened, which causes the absorption of a larger amount of the anesthetic, and therefore the patient is brought into the state of surgical anesthesia quicker; at the same time, this procedure is safer, inasmuch as the carbon dioxide by stimulating respiration, tends to prevent spasm of the respiratory muscles — the chief source of danger in the induction period. After the stage of surgical anesthesia has been reached the rate of administration should be decreased, but regulated at all times by the patient's condition and the depth of anesthesia required. It is to be particularly noticed that from the beginning till the close of the administration, the ether is added drop by drop and therefore the vapor is never concentrated, and after the induction it is practically uniform in both strength and temperature. Unnecessary irrita- tion and injury to the respiratory passage^ are con- sequently prevented. The prevention of shock, so far as acapnia is con- cerned, lies in maintaining a normal amount of carbon dioxide in the blood. Such anesthetics as ether that stimulate respiration produce acapnia by overventilation of the lungs, consequently there is a special indication for the rebreathing of ether so as to maintain the carbon dioxide at a normal level. In nearly all of the specially designed apparatuses used in this country for the administration of ether by the closed method, the amount of rebreathing is governed by the air supply or oxygenation. In other words, the rebreathing cannot be increased beyond the point where the air supply barely furnishes sufficient oxygen, for to increase the rebreathing is to decrease the air supply. Since with ether it is necessary to have rebreathing to prevent acapnia, for ordinary conditions there is usually a sufficient amount of rebreathing when the air supply is restricted as much 379 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES as proper oxygenation will allow, but, as carbon dioxide readily transpires through the thin walls of the capillaries whenever there is a considerable exposure of these vessels, in abdominal operations with the viscera much exposed, there is such a marked and direct loss of carbon dioxide from this source that the rcbreathing must be markedly increased over S3078 Fig. 221. — Pynchon Apparatus. that necessary in ordinary conditions in order still to maintain the carbon dioxide at a normal level. To meet this condition, either the air supply should be further restricted, thereby increasing the rebreathing, pure oxygen being added to the rebreathing bag, or with the air supply sufficient for oxygenation carbon dioxide gas should be added to the bag. Accordingly in the apparatus which the author uses there is provision for a cylinder of nitrous oxide for the induction of anesthesia, and a cylinder each of oxygen and carbon dioxide for instantaneous use whenever indicated, either in routine or emergency work. A mixture of carbon dioxide and oxygen is also very useful, and can be attached to the same stand. Each of the four different cylinders is in direct connection with the rebreathing bag, and all are easily wheeled about the room and kept entirely out of the way of the surgeon and assistant- at all times. The Insufflation Method. — In some operations, especially about the face, it is impossible to use a mask, and then it becomes either desirable or Fig necessary to force the vapor through a flexible tube, placed either in the mouth or nares. With such a method of administration the mouth, nares, and throatare perfectly accessible throughout a pro- longed anesthesia, and the anesthetist is at quite a distance from the patient's face so as to be completely out of the way of the surgeon and his assistants. The Pynchon inhaler (Fig. 221) is very simple and compact and well exemplifies the essentials of this Fig. 222. — Paine's Nasal Catheter. form of apparatus. It consists of two large-mouthed bottles (about eight ounces) connected together with a screw-cap metal fitting; one bottle contains ether, and the other acts as a mixing or safety chamber, and has located within it also a small bottle for chloroform. Connected with the ether bottle is a ten ounce Politzer foot-bulb for forcing an air current 380 through the ether, and for carrying the vapor onward to the patient's respiratory passages. The bag carries an air-inlet valve, and in the tubing between the bag and ether bottle is another valve to prevent suction of ether or vapor back into the bag when the latter is expanding after being compressed. To the other or safety bottle, is attached a small rubber tube which leads to the patient's respiratory passages. This tubing may be terminated in one of several different methods, depending chiefly upon the requirementa of the individual case. The illustration (Fig. 221) shows it. terminating in two nasal tips which, when of the proper size, fit tightly into the nares. Instead of the nasal tips, nasal catheters (Fig. 222) may be attached to the tubing by means of a Y-fitting, and often only one such catheter is needed. Instead of these nasal fittings the tubing may be attached to a special gag such as a Ferguson, with anesthetic tubes added, which distributes the vapor well within the mouth as well as acting as a gag. The tubing may also be connected with a mouth tube, or the regular tracheotomy tube, and in certain instances become most useful in the maintenance of anesthesia. Many other end attachments for the efferent tubing will be found serviceable. Within the safety bottle, which is large enough to prevent any ether being pumped through the tubing which leads to the patient's respiratory passages in case a large volume of air is suddenly forced into the ether bottle, is placed a small bottle for chloroform. The chloroform is forced out of this bottle by a small hand bulb and made to drop into the larger bottle in the original apparatus. Kilmer's suggestion is good, that a little gauze be placed just beneath the metal tube that leads from the chloroform bottle, and as the hand bulb is compressed the chloroform drops upon this gauze, and is rapidly vaporized by the air, or etherized air current that passes into the mixing bottle. At all other times the ether vapor passes through this mixing bottle without t he absorption of any chloroform. 223. — Coburn Apparatus for Administering all Liquid Anesthetics by the Insufflation Method. The apparatus is light and may be conveniently hooked or pinned to the anesthetist's coat or gown. The Coburn apparatus is also well adapted for this form of administration, the mask, chamber, cup, and heater being used (Fig. 223). The mask and heater maintain the cup in an upright position. Into the opening of the chamber is inserted a stopper to which is connected the tubing that leads to the Politzer bag. In the opening within the mask is inserted another stopper to which tubing is attached that leads to a small "safety bottle." and connected with this bottle is also the tubing that leads to the patient's respira- tory passages. The administration of ether is con- trolled by the needle valve, and any desired strength of vapor or rate of administration may be attained in this, as in all other methods. Chloroform may be added to the "safety bottle,"' if the addition of this anesthetic is desired at any time. In most of the cases in which this method is well REFERENCE IIAXDIK >< >K OF THE MEDICAL SCIENCES Anesthesia, General Surgical suited there is considerable advantage in using a I,, bulb to force the air current through the appara- tus for the compressions of tin' bulb can be timed with the patient's inspirations and little or ither wasted or blown into the surgeon's face. When two bulbs are used the vapor current is continuous, an.l much of it is wasted by the patient's expirations ami blown out into the surgeon's face. Ordinarily the patient i.-- anesthetized in the 1 usual manner, preferably by gas-ether sequence, and the anesthesia continued with some special apparatus. However, the patient may be primarily anesthetized with an insufflation apparatus by connecting the of the efferent tubing with a face mask covered with rubber, and the vapor then pumped into this mask. If the operation is to be in the throat, after the patient is anesthetized either the nasal tips or catheters are fitted into the nares, and the vapor thus pumped through the nasal passages, or the end of the afferent lulling is connected to a modified Ferguson gag or metal mouth tube and the vapor thus forced into the oral cavity. This method of procedure is to be much preferred to that of an intermittent anesthetization for ations within the mouth or throat, where the original anesthesia does not last till the completion of the operation. Henderson lias clearly shown that in- termittent anesthetization is highly conducive to shock, and may even cause primary heart failure in normal subjects; consequently the method of anes- thetizing deeply with ether in tonsillectomies ami similar work, then removing the mask and reapplying it when the patient begins to recover, deeply anes- thetizing again, and again removing the mask, is to be severely criticised. Furthermore, in tonsillectomies chloroform should not be used even in conjunction with ether vapor, although the apparatus is well adapted for such a combination, for in this class of operations chloroform has been found to be extremely dangerous. Fig. 22i. — The Jauway Apparatus; front veiw. The method just described has been called the "Vapor Method," but this is a misnomer, for all in- halation anesthetics are administered as a vapor, ami consequently they are all vapor methods. Intratracheal Insufflation. — To Meltzer and Auer the profession is indebted for the developing and perfecting of the intratracheal insufflation method of anesthesia. The essentials of this method consist in the introduction deep into the trachea of a flexible tube, the diameter of which is considerably less than that of the lumen of the trachea and the forcing through this tube of the anesthesic vapor, the excess i if air and vapor and the products of respiration passing out through the space between the tube and the walls of the trachea. The essentials as thus outlined, are very few, and quite easily attained. Apparatus, however, for this method of administration is usually quite elaborate and complicated, not because of absolute necessity, but rat her to render the method of administration as nearly automatic as possible, and to guard against dangers which are more or 1 1 etical. The .laneway apparatus (figs. 224 and 225) is com- pact portable, and will be briefly described. It con- sists of an electrically driven fan for forcing a st< air stream through I he apparatus and finally into i in- patient's trachea. A valve deviate- any de ired portion of this air stream so that il pa se over liquid ether, thereby furnishing the anesthetic vapor. The ether vapor and air then pass over water kept hot by an electric heater; from this warming-moisten- ing bottle the etherized air passes into a small con- 1 rrr^ 1 1 imiL^ Fig. 225. — The Janeway Apparatus; back view. denser, removing the excess moisture, and then it passes through a small rubber tube several feet in length to the catheter introduced into the patient's trachea. The hot water heats and moistens the ether vapor and air. Connecting with the tubing which leads to the trachea is a mercury manometer which registers the intratubular pressure. The in- tratracheal pressure is usually one-fourth of the in- tratubular pressure. It is very important that the pressure be neither too high nor too low. If the intratracheal pressure is too high death may easily be caused by rupture of the lungs and if this pressure is too low an insufficient amount of air will be supplied to the lungs and consequently oxygenation will be low. Usually a pressure of twenty millimeters fulfils all requirements. Increasing the pressure decreases the muscular respiratory movement. Accordingly, if the respiratory movement impedes the work of the surgeon, the pressure may be increased up to thirty millimeters, but it is dangerous to in- crease it much beyond this amount. On account of the danger connected with an ex- cessive intratracheal pressure, especially if sudden, it is advisable to use a "safety valve." This is con- nected with the etherized air current and the height of the mercury column is such that the mercury blows out when the pressure exceeds a certain point. The safety valve may be set at any desired pressure, usually forty millimeters, and unless the air current is absolutely constant and reliable it adds a great ele- ment of safety to this method of anesthesia. An interrupter is operated by the electrically driven motor so as to interrupt the air-ether current every few seconds. The frequent interruption of the current entering the lungs is an element of safety in the method. There is also an air filter near the fan. Instead of the electrically operated fan a foot bellows may be used, and even if the former is used a bellows should alway-s be conveniently at hand ready for use in case of an accident in the electric service or mechanism. 3S1 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES An extremely simple and portable apparatus for the intratracheal method of administration is the Coburn apparatus as shown in Fig. 223, with the following changes: A foot bellows is substituted for the Politzer bag; a pressure dropping cup is sub- stituted for the regular cup; and a manometer and a "safety valve" are connected with the efferent tubing. .Much of the success and safety of the anesthesia depend upon the size of the catheter introduced into the trachea, as well as upon the method of its intro- duction. If the catheter is too small the return current is so rapid that too small an amount of the .•mi -i lutic is absorbed, and therefore the anesthesia is too light. If the catheter is too large it offers too much obstruction to the return current, and the intratracheal pressure becomes too high, approaching that of the tube registered by the manometer. The end of the catheter should be introduced to a point about three centimeters above the bifurcation of the trachea. If the catheter is introduced too far it pro- duces overdistention of a lung, and if it is not introduced far enough not a sufficient amount of the anesthetic and air reaches the alveoli of the lungs, and consequently the anesthesia is too light and oxygenation incomplete. Finally, the catheter is sometimes passed into the esophagus instead of the trachea, and the stomach is thereby inflated. Just prior to use the apparatus should be connected up and tested in order to insure that it is in good working order. The size of the catheter should be selected according to the size of the glottis. The proper size for adults is usually 22 French, and in order to facilitate its introduction it should be a silk woven catheter, the plain rubber being too pliable. While the catheter must, of course, be flexible, it must not be too pliable, for in its introduc- tion the fingers or holder are several centimeters distant from the glottis, and in passing it through the glottis down into the trachea, there is sonic little resistance. If the catheter is too pliable it will curl upon itself instead of passing on down into the trachea, and if it is too rigid it will not adapt its shape to the necessary curves. The silk woven variety has been found to answer all the various requirements. The point to which the catheter should be introduced is, in the adult, about twenty-six centimeters from the teeth, so an indelible ring should be marked on the catheter twenty-six centimeters from the internal end. As the glottis is about thir- teen centimeters from the teeth it is well to have another such a ring thirteen centimeters from the end to be introduced. The catheter should, of course, be sterile and lubricated. While not absolutely necessary it is advisable to have the patient deeply anesthetized, preferably with ether, just prior to the introduction of the catheter so the muscles about the head and neck will be relaxed, and so that the patient's reflexes will not recover and displace the catheter by coughing before the intratracheal insufflation of the anesthetic can be started. After the mask has been removed the patient is quickly moved on the table so the head and neck are clear of the edge, and a mouth gag is inserted. An assistant then places one hand at the back of the patient's neck and presses upward, and grasps the forehead with the other hand and presses downward The tongue is then pulled forward and a Jackson laryngoscope passed over its base, the epiglottis is identified and the laryngoscope passed over it also, and as the larynx is completely exposed, the catheter is passed between the vocal cords down to the indi- cated mark. While it requires a little experience to make the introduction deftly the necessary skill is usually acquired readily. Special introducers have been designed lo facilitate the introduction of the cat liefer, but 1 he I hod and means here outlined are practical, convenient, and efficient, and are quite generally employed. As soon as the catheter .has been introduced the proper distance a special examination should be made to determine whether it was actually introduced into the trachea, as intended, or into the esophagus, as has frequently been the case. If air passes in and out of the catheter with the patient's respirations, of course it has been introduced into the trachea. Tin- respiratory movements can be heard or felt at the external end of the catheter. A very positive way to determine this matter is to place the end of the catheter near the top surface of some water in a small vessel, and if the catheter is in the trachea the expiratory current will make a distinct depres and disturbance on the surface of the water. ( if course, if the catheter is found by any of these means to be in the esophagus, it should be immedi- ately withdrawn and properly introduced into the trachea. After one is assured that the catheter is in proper position, a metal protector is slipped over the catheter to prevent its being closed at any time by the patient's teeth, the gag is removed, the patient is moved down on the table, and the catheter is connected with the tubing that leads from the apparatus. When the etherized air stream is forced into the trachea it is advisable to take the precaution to anchor the cathe- ter with a strip of adhesive plaster to prevent its displacement should the patient cough. As soon as the air current is started through the intratracheal catheter the patient should be watched carefully for the first minute or two for evidence of faulty' introduction of the catheter, for herein lies much of the clanger connected with this method of an- esthesia. If it has been introduced into the esophagus instead of the trachea the stomach will be rapidly and dangerously inflated. Should this accident occur the tubing must be immediately disconnected from the catheter, the stomach emptied, the catheter with- drawn and then properly introduced. If the catheter has been passed too far into the trachea the end may reach one of the bronchi (usually the right), and through hyperdistention of the lung rapidly cause pneumothorax. Should there be evi- dence of too low an introduction the catheter must be immediately withdrawn a few centimeters so that the end rests about three centimeters above the right bronchus. By the time the catheter is properly introduced and connected with the apparatus the patient may begin to show signs of recovery, so for the first few minutes it is usually necessary to use quite a strong vapor, but the strength of the vapor, as in all other methods of administration, must be regulated according to the individual requirements and the indications of the particular case at hand. The strength of the vapor is easily regulated by turning the valve on the Janeway apparatus which controls the amount of the air current that passes over the liquid ether, and this valve may be set so that it may run for many minutes without any change or manipulation of any other part of the apparatus. As the air current passes over the ether, and not through it, the maxi- mum amount of ether that may thus be administered to the patient is limited, but for most patients it is sufficient to secure complete anesthesia with relaxa- tion. In the Coburn apparatus the administration of ether is controlled by the needle valve, just as it is with all other methods. The amount of ether used slightly exceeds that of other methods, but the patient does not absorb as much, as the return current quickly carries the excess out of the lungs. Nitrous oxide and oxygen may also be used as the anesthetic, the general principle involved being the -: as that for ether, except no fan or bellows is re- quired, since both gases are under pressure, and when expanded furnish sufficient power to force the an- esthetic stream automatically through the tubing and catheter. :',s-2 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia! General Surgical The advantages of this method oi anesthesia are many and distinct, especially in the field for which it Is particularly well adapted, and its pronounced benefits are not limited to thoracic surgery for which ii was originally intended. Willi this method of anes- thesia the che I cavity may be opened with impunity. It ^ also highly useful in operations within the mouth or upon the tongue or upper respiratory tract as 1 1 n- mums outward flowing stream of air prevents |, infectious and other material from reaching lower respiratory tract or interfering in any way with respiration, it is also useful in operations ; the face, head, and neck when the usual face mask cannot lie used or when it is desirable to have t he anesthetist away from the field of operation. Finally, it is useful in operations where the usual respiratory movement interferes with the work of the surgeon and where there is continuous vomiting, as in intestinal obstruction. Diffi rential Pressure. — The work of Sauerbruck and Brauer first made possible and feasible the open- ing of the chest cavity for surgical purposes, the one using positive, and the other negative pressure. Connected with each form of apparatus, however, were many deficiencies and difficulties. Willy .\le\ er bined the two methods into one apparatus, over- most of the difficulties, added original improve- it 5, and perfected a system of differential pressure thai completely fulfils all of the requirements for thoracic surgery. The Meyer differential pressure apparatus consists of a positive chamber within a negative chamber, and the necessary means for ven- tilating and controlling the pressure in both cham- bers. The positive chamber is of sufficient size so that the anesthetist may have plenty of room for himself and supplies. The patient's head is placed jusl within the positive chamber, and the body lies on the table in the outer or negative chamber. A sheet of rubber is drawn snugly around the patient's neck to make the inner or positive chamber air-tight when the door leading into the same is closed. The negative chamber is sufficiently large for the table, the surgeon, his assistants, and necessary paraphernalia. With this apparatus any desired negative or posi- tive pressure may be secured or any desired combina- tion of negative and positive pressure, or a change from either pressure to the other, and artificial respiration may be had at any time. The different anesthetics are administered in the usual manner when using the Meyer differential pres- sure apparatus. Nitrous oxide and oxygen may be administered under sufficient positive pressure for thoracic surgery without any special apparatus. The supply of gases must be continuous, the mask very accurately fitted to the face, and the exhaling valve closed by a coiled spring set at the desired pressure. The gas bags must be kept distended sufficiently to open the expiratory valve slightly during expiration. Otherwise the ad- ministration is the same as at normal pressure. The Administration of Anesthetics in Conjunction with Pure Oxygen. — The intimate physiology of anesthesia is closely associated with the oxidation of the brain cells. In the prolonged administration of nitrous oxide the amount of oxygen required approxi- mates that required under ordinary circumstances. and the same may be said regarding all administra- tions of chloroform. With ether and ethyl chloride, however, there are some advantages in limiting the Oxvgen supply in normal or robust subjects. In the delicate and debilitated subject, on the other hand, there is an advantage in increasing the normal oxygen supply. The administration of pure oxygen in conjunction with nitrous oxide and ether in the closed method has already been described. If the condition of the patient is such that there is need of increasing the normal supply "i oxygen in the administration of ethyl chloride (with exceptional cases in thi <' in, . 1 .... 1 1 i In ane I het ic i ab olutelj cont i aindicated. I I....' remains ft .1 con ii lera 1 ii in here, t hen. 1 he administration of chloroform, anesthol, and ether by the open method, and for this purpose no special apparatus is required. T) xygen is allowed to bubble through the water slowly, and the end of the efferent i u I h • i- pi,-..-,, | beneath the patient's nare , the tube extending through or beneath the ma 1. With the Coburn apparatus the end of the tube is extended into the chamber, and is held in position by the gauze. Will, the Pynchon and Junker inhalers the efferent tube is attached to the apparatus so thai the oxygen passes through the liquid anesthetic, \ apprizing it, instead of air. The advantages of administering oxygen in con- junction with ether, chloroform, and anesthol are that, in debilitated subjects, it conserves the patient's vitality and t he post narcotic ell eels are less pronounced. Rectal Etherization. — Very soon after the anesthetic properties of ether were demonstrated bj pulmonary administration Etoux, in 1M7, suggested its admin- istration per rectum. Pirogoff, during the same year, so administered it upon the human subject, using liquid ether mixed with water, the chief object in view being to facilitate the performance of operations within and about the moiilh, nose, and pharynx. The method was tried by a few others, and it was soon learned that t he administration of the vapor was followed by better results than that of the liquid ether, either pure or diluted with water. Little attention, however, was given to this method of administration for several decades, when Molliere, in 1884, after quite an extensive trial, reported favor- ably concerning it. Weir, the same year, reported t he death of an eight months child from rectal etherization, the operation being for harelip. Death occurred from melena within twenty-four hours after the operation. Bull, the same year, reported seventeen cases of rectal etherization, but the results were unsatisfactory, for not only did melena and diarrhea supervene in some of the cases, but others had prolonged and profound stupor, and asphyxia! symptoms. Buxton has used this method and finds it to answer admirably for operations about the mouth, nose, postbuccal cavities, and larynx, and for operations for the relief of empyema. Cunningham in 1S9S reported forty-one cases, there being no deaths, diarrhea, or bloody stools. Leggett, in 1907, had a series of thirty-one cases, with anesthesia incomplete in three cases, and with bloody stools in one case, but no deaths. In this form of administration it is absolutely essential that the bowels be empty, for the feces will not only prevent the absorption of the anesthetic but will also plug the rectal tube. The Pynchon apparatus previously described (Fig. 221), is admirably suited for this method of administration. The Coburn apparatus with the insufflation attachments (Fig. 223), may likewise be used if a pressure dropping cup is substituted for the regular cup. An efficient apparatus is easily im- provised by using an ordinary graduated flask, having a rubber cork with two holes. Into one of the holes insert a rod nearly to the bottom of the flask, and into the other hole insert a short rod that extends just through the cork. Connect the long rod to a Politzer bag and the short rod to a small rubber tube one meter long. Fill the flask one-third full of ether. A double current rectal tube is used, the ether vapor entering through one tube and the excess vapor and gases escaping through the other tube, the end of which tubing is immersed in alcohol to the depth of three or four centimeters. When wanning de- vices are used they should be placed as close to the I patient as possible so that the vapor may not be cooled 383 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES before it reaches the rectum, as warm vapor cools very rapidly. After inserting the tube high into the rectum and connecting it to the efferent tube of the apparatus, the vapor is slowly pumped into the rectum, the excess vapor returning through the escape tube, as de- scribed. It requires longer to anesthetize with this method than with the pulmonary methods, but the signs of anesthesia are the same, and similar care must be exercised at all times to see that the respiratory movement is free ami unobstructed. Advantages and Disadvantages of Rectal Etheriza- tion. — Prior to the perfection of the insufflation methods, and of nitrous oxide-oxygen anesthe ia, rectal etherization had some practical advantages, inasmuch as it prevents, to a very great extent, the irritant action of pulmonary methods of administra- tion of ether upon the respiratory tract, displaces the face mask, and removes the anesthetist away from the patient's head. However, all the advantages of rectal etherization can be better secured by the methods and anesthetic just mentioned without the slow induction, uncertain anesthesia, rectal irritation and diarrhea that so often follow the rectal method, Besides, its death rate has been the highest of any method described in this resume. Intravenous Etherization. — The direct introduction of anesthetics into the vascular system has attracted considerable attention during the past few years, and during the past year considerable use, both practical and experimental, has been made of this method of administering ether. Five per cent, of ether in normal saline solution is usually employed. At first the administration was conducted with an intermit- tent introduction of the dilute ether into the vein, but the interruption of the stream had a tendency to cause the formation of thromboses in and about the cannula. A continuous, but slower rate of adminis- tration, however, overcame this objection and at the same time the resulting anesthesia was more satis- factory inasmuch as it was smooth and even. The apparatus used successfully by Rood is simple, practical, and satisfactory. The ether, diluted with ninety-five per cent, saline solution, is held in a. reser- voir placed about eight feet above the floor. Rubber tubing with a pipette attached leads from the bottom of the reservoir to a chamber, the pipette being within the latter. From the bottom of the chamber rubber tubing leads to a warming bottle and thence to the cannula into the vein. There is a shut-off below tin 1 chamber to control the rate of administration and there should be one above the chamber to control the rate of flow into it. As the ether solution drops from the pipette the rate of flow can be plainly seen, and regulated according to the special requirements. It is preferable to give the preliminary hypodermic of morphine and atropine, or morphine and hyoscine The arm is lightly bandaged to a splint to prevent flexion at the elbow. Eucaine is then injected locally, and the vein exposed by a one-third inch incision. The cannula is properly tied in the vein, and the wound packed with sterile gauze, strict asepsis being observed through the procedure. The ether solution is allowed to flow rapidly until the patient is anesthetized, which requires about ten minutes of time and eight ounces of the solution. After anes- thesia is established the rate of administration is much slower, about sixteen ounces of the solution per hour being ordinarily sufficient. Rood reports one case of three and one-half hours administration, in which four and one-half ounces of ether and four and one-half pints of saline solution were used, and several cases of over two hours dura l ion. The advantages claimed are: (1) The anesthesia is delicately controlled; (2) early return of conscious- ness; (3) postanesthetic vomiting and pulmonary irritation are rare; (4) saline infusion per se is of benefit sometimes. Chloroform. — In the administration of chloroform it is quite essential that the air supply be unrestricted, consequently it is always administered by the open system, but by a variety of methods. The open drop method is the most popular method in this country. Any open mask such as Esmarch's or Schimmelbusch's covered with a single layer of flan- nel, or a few layers of gauze, is well adapted for the open administration. On account of the local irritant properties of chloroform the skin beneath the mask should be protected with vaseline, cold cream, or some such preparation. The chief source of immediate danger in the ad- ministration of this anesthetic is "overdosage." It is ordinarily stated that the percentage of the chloroform vapor is too high, but the percentage of the vapor that the patient may safely inspire de- pends upon the rate and depth of respiration, and is therefore variable. With the ordinary rhythm and volume of respiratory movement it is generally con- sidered that a two per cent, vapor is the maximum amount that the patient may safely inspire, but there are circumstances, such as deep and rapid respiration after an apnea from muscular spasm, holding the breath, and other respiratory impedi- ments, when this percentage might be excessive. Accordingly, in the induction of this form of anesthesia especially the anesthetist, must gauge the strength of the vapor according to the patient's respiration, particularly when he is not dealing with known percentages. Fig. 226. — Esmarch's Mask and Dropper. When chloroform is exposed to light it decomposes and is rendered unfit for use. Therefore, it should be purchased in small, strongly colored, and well stoppered bottles. Chloroform vapor when exposed to an open flame is decomposed into irritating gases, which apparently affect the other occupants of the room more than they do the patient. If it is neces- sary to have an open light in the room it should be placed as high as possible, as the anesthetic vapor is heavier than air, and therefore tends to settle down- ward. The fumes of ammonia are said to combine with the chlorine and other irritating gases liberated in this decomposition of chloroform, and render them innocuous. In order to reduce the size of the drop a special dropper such as the Esmarch's or Filling's should be used, as the rate of administration is much easier controlled if the drop is small. The Coburn appara- tus also has such a special dropper for the open administration of chloroform. The dropping of the anesthetic should be very slow at first and gradually increased. Coughing, holding the breath, :;m REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anegtne ,ia, General Surgical or muscular spasm indicates that the vapor is too strong, and whenever such symptoms occur the rate of administration must be decreased, or withheld altogether temporarily, until normal respiration is resumed. Excitement, struggling, crying, etc., in this method of induction arc especially dangerous, and if such conditions cannot be prevented, the anes- thetist must be very careful that the patient does not suddenly make a deep respiration of a strong vapor, for just a single inspiration of this character may lie followed by fatal results. Under no circumstances, should the induction be unduly hastened, as some- FlG. 227. — Junker's Inhaler. times it requires seven or eight minutes to anesthetize completely with chloroform. Junker's Inhaler (Fig. 227) or one of its various modifications is very useful in administering chloroform, especially in operations within or about the mouth, nose, or pharynx. In inducing the anesthesia a face mask is employed, and the vapor is slowly pumped through the tubing by compressing the bulb during inspiration. After full anesthesia is secured, if the operation is of such a character that the face mask would interfere with the work of the surgeon the end of the efferent tube should be connected with a curved metal tube or to a gag with anesthetic tubes or to a nasal catheter (Fig. 222), and the vapor thus forced into the respira- tory passages. In using a Junker inhaler care must be exercised not to compress the bulb too rapidly or too vigor- ously, for liquid chloroform may be easily forced into the patient's respiratory pas- sages. Several deaths from this accident have been reported. The Trendelenburg apparatus (Fig. 228) is sometimes used for the administration of chloroform when a tracheotomy has previ- ously been performed. The anesthetic is added by the drop method. The Harcourt inhaler (Fig. 229) is quite extensively used in England, and very ac- curately regulates the percentage of chloro- form vapor, it being practically impossible to exceed the maximum limit of two per cent. Inasmuch as with this inhaler air is always well mixed with the vapor, and any strength of vapor up to two per cent. can be obtained, it affords a very safe means for the administration of chloroform when a face mask may be continuously applied. Chloroform mixtures, such as A. C. E. and C. E., and chloroform preparations, such as anesthol, should always be administered by the open system, as the chloroform content makes it unsafe to limit in any way the oxygen supply, and, at the same time, renders it imperative that the strength of vapor be as constant as possible, so as not to exceed the limit of safety. When air is passed through any of these mixtures or preparations to vaporize them the unequal rates of volatility of the several ingredients cause the vapor to Vol. I.— 25 vary in composition. All of these anesthetics are administered in somewhat larger quantities than chloroform, but is lesser quantities than ether. The advantages oi the chloroform mixtures and preparations are that they are less irritating to the respiratory tract than ether, and less depressing than chloroform. The s ial advantages claimed forane thol (li per cent, ethyl chloride, 35.89 per cent, chloroform, and 47.11 per cent, ether) are: Ashorl induction without excitement or struggling; no increase in saliva or mucus; early recoverj of consciousness; and no irritation of limns or kidneys. [ts specific gravity is 1045, being close to that of the blood;' and its boiling-point is 104° F., be- ing close to the temperature of the blood. Alkaloidal Anesthesia. — For many centuries past (see the introductory para- graph) more or less complete analgesia and anesthesia were secured by the administra- tion of various preparations of different plains and herbs. However, throughalack of knowledge, either in preparation or ad- ministration, this primitive and primal form of anesthesia was then never widely utilized for surgical purposes, and for many years was completely superceded by the inhalation anesthesia already outlined. The advent of the modern laboratory means of investigation, combined with more careful clinical observation clearly showing the detrimental and far-reaching remote effects of the inhalation anesthetics usually employed, has led to a partial reversion, at least, to the original method of attempted anesthesia, refined, of course, by modern means of preparation and methods of ad- ministration. To-day it is the physiologically tested alkaloid rather than uncertain and inert substances; it is the hypodermic solution, not the decoction. The alkaloids most commonly used for this pur- pose are morphine, atropine, hyoscine, and scopolam- ine. As hyoscine and scopolamine are so nearly, if not entirely identical in both composition and physio- logical action, many authorities consider them identi- cal, and that view is here followed. The effect of hyoscine alone is quite uncertain, but when combined 'with such an active syngerist as Fig. 228. — Trendelenburg's Trachea Tampon and Inhaler. morphine the anesthetic action is positive, though not reliable unless excessive amounts are given. For complete anesthesia one-fourth grain of mor- phine and one one-hundredth grain of hyoscine are given hypodermically, three hours before the time set for the operation and repeated at the end of two hours in the original or decreased dosage, according to the patient's condition. Fifteen minutes before the opera- tion another injection is given, if the patient is not already anesthetized. While quite a number of successful reports have been made by a number of writers of such use of these anesthetics, there have 385 Anesthesia, General Surgical REFERENCE HANDBOOK OF THE MEDICAL SCIENCES likewise been quite a number of failures and fatalities reported. Accordingly, this method for the induction of complete surgical anesthesia is quite generally condemned. But while the dose of alkaloids alone for the production of complete surgical anesthesia is so large and is attended with so much danger that their use for this purpose has been practically abandoned, the toxicity is so low in medium dosage that they are quite generally employed for analgesia, and as a preliminary to the inhalation anesthetics. For these purposes a single, medium-sized dose is given hypodermically. In obstetrical practice, in which the com- bination of mor- phine and hyoscine has been so widely lauded by enthu- siasts, both the child and mother need to be closely watched for several hours, and the dose of hyoscine usually recommended i s too large to be safe. In general it may be said that the maximum dose for the robust adult male is one-fourth grain morphine, and one one-hun- dredth grain hyos- cine, and for the female about two- third s of this amount, and lesser amounts, of course, where the individ- ual is under-sized, or where the phys- ical condition is impaired, or the patient is above fifty years of age; and this medica- tion should not be repeated for at least several hours. The value of morphine alone, or combined with some other alkaloid, as a preliminary to other anesthetics, has been discussed elsewhere in this article. It may be further said that this practice is approved by the leading anesthetists throughout the civilized world. There is, therefore, a decided and growing tendency to combine the alkaloidal and inhalation anesthetics in the most approved production of modern anesthesia. Electric Anesthesia. — Electric anesthesia is in- duced by a direct current interrupted a great number of times per minute, and connected to the body by electrodes. It is important that the potential of the current be limited to a little more than that required for the anesthesia, for otherwise it is very easy to electrocute instead of only to anesthetize the subject. The number of interruptions for anesthesia should be 6,000 to 7,000 per minute, and the period of the passage of the current one-tenth of the entire time. Storage batteries afford the best form of direct current. Apparatus. — The special paraphernalia needed are storage batteries and connections, a rheostat, two meters, one for voltage, and the other for amperage, a make-and-break switch, electrodes, and a Leduc or Robinovitch interrupter. Technique. — The negative pole is connected to the head electrode and the positive pole is connected to the electrode applied at the lower end of the spine. It is quite important that the cathode should always be applied to the head, for if the anode is applied there instead, respiration is impeded, and death is much more likely to follow, even with the same Fig. 229. — Harcourt's Chloroform Inhaler. potential. Before applying the electrodes, in animal experimentation, the fur, at the point of application is first cut away and the skin shaved, care being exer- cised not to cut the skin. The shaved spots are washed with alcohol, and then covered with a thin layer of cotton wet with saline solution. The elec- trodes are then applied to the wet cotton, and the circuit is closed on a low potential. As the voltage is increased, there is slight struggling of the animal, but loss of consciousness soon follows. If the potential is increased too much, respiration becomes labored and convulsions follow, and this state can be relieved only by reducing the voltage. The respiration is therefore the best single guide in the proper main- tenance of electric anesthesia, just as it is with the inhalation anesthetics. Utility. — Thus far electric anesthesia for surgical purposes has been used chiefly for experimental work on animals, and when skilfully handled it is a very safe form of anesthesia. The postanesthetic effects are practically nil. Recovery takes place as soon as the current is opened. Johnson reports one case in the human subject, successfully anesthetized for forty-five minutes for the amputation of several toes. Raymond C. Coburx. Anesthesia, Local. — General anesthesia and spinal anesthesia (or analgesia) are studied elsewhere in this work under these respective headings. Before discussing local anesthesia it may be as well, in view of the increasing tendency toward accurate terminol- ogy, to say that quite frequently, now, analgesia is employed rather than anesthesia, as indicating, properly, a condition of absence of pain; whereas anesthesia really means only absence of common sensation. After the employment of both spinal and local means against painful operating it is not unusual for a measure of common sensation to be retained in the region in question, whereas pain may be wholly absent (analgesia). The subject of local as distinguished from general anesthesia is one of increasing importance, year by year. Far more operations are done by such help (in- cluding spinal analgesia) at present than was the case even a few years ago. The main reason for this change is the fear so general among all mankind of being forced into unconsciousness; and this is as prevalent among physicians as laymen. Argument, proving the almost invariable safety of ether, chloro- form, etc., in skilled hands, does not change the fact that people often dread the oblivion more than the knife. In the earlier years of the local use of cocaine and a few other drugs in surgery there were enough mistakes made and unsatisfactory results from one or another cause to justify the limitation of "minor anesthesia" to minor work; but latterly, with our present knowledge of ways and means, there are few fields of operative endeavor that have not been successfully invaded by the surgeon, his patient feeling no pain, although entirely conscious, and often chatting interestedly meantime. It follows from this, that many a patient needing a radical cure of hernia, or interval appendicitis operation — to mention one or two among large numbers — will to-day readily submit to being operated upon, who would formerly have hesitated and postponed, chiefly because of the major anesthesia dread, until operation became com- pulsory, and very possibly until too late for safe surgery. Of course there are exceptions, both in kind of operation under discussion and in nature of patient in question. It would take us too far afield to go into these. There will always remain an abundant field for major anesthesia; but nevertheless the rapid development of local analgesia instead of that demand- ing unconsciousness is a noticeable sign of the times. To discuss our topic in an orderly way let us study it as follows: Local anesthesia produced by aid of cold, of light, of sinusoidal electric energy, by analgesic 386 REFERENCE IIAXIHtook ( >F Till' MEDICAL SCIENCES Anesthesia, Local tr chemicals applied to skin or raucous membrane, or con- veyed in deeper parts by aid of the hypodermic needle, i ric catapnoresis and by intravenous injection (,nii.— In increasing degree of intensity we ibility by application of ice-water or ice, iray of benzine or rhigolene or gasoline, by of ethyl chloride, by application of carbonic- snow, or by liquid air. Ihe last named is destructiv< — is too inter elj cold for practical purposes. Even C0 2 ice turns the ^ k i r i a corpse-white instantly, ami contact with it for longer than a few seconds will not only freeze but will destiny vitality -and it is an ideal agent for this purpose in attacking superficial growths. Ethyl chloride as to degree of cold, may be said to represent a mean between extremes, ami is our choice for local esia by chilling. Applied as a spray ii pro- duces the corpse-white, which means insensibility, in econds, but if cutting deeply — as to the bone in felon — is needed, the freezing must be continued some longer. If, however, several minutes, of solidly frozen flesh result from its prolonged use, the tatient may complain of the aching, just as from rost-hite or chilblains subsequently. Where benzine or rhigolene spray, or ice-application must be de- pended upon for freezing it is best to begin, wherever Eossible, by cording firmly; for example, with felon, y snapping an elastic band several times about the finger at its palmar juncture. Thus the chilled blood is not -wept away and replaced by heated for some time' before freezing occurs, and considerable suffer- ing is spared the patient by the saving in time of exposure to the cold. Thi method of local anesthesia under discussion (i.e. freezing by any means) should be employed, in operating, for only one purpose, namely, to make one or several cuts for the relief of pus or of inflammatory tension. It is not a desirable choice where there needs to be careful dissection — the flesh being frozen solid as deeply as the knife is to penetrate, if pain is to be entirely obviated. Analgesic Drugs. — Water. — Under this second heading water should first be mentioned, because for rations it has been recognized as having analgesic qualities. In Bartholow's Materia Medica (Third Edition, 1S79), under the heading of Aquapuncture, for example, it is affirmed that some physicians in giving a hypodermic injection of a watery solution of morphine attribute the subsequent relief from pain more to the water than to the morphine! While by no means going so far as this, the writer, in common with many practitioners can claim often to have observed in severe sciatica, for instance, much relief from pure water injected by needle either into or in contact with the sciatic nerve. Balsted, nearly thirty years ago, suggested and employed water for this purpose, injecting it, for ex- ample, all about and beneath superficial tumors, which could be then removed painlessly. In the arti- cle on Subcutaneous Emphysema in the first edition of this Handbook the present writer detailed his ex- periments upon his own person in an endeavor to rtain whether mere pressure alone upon the "ry nerve-endings would suffice to benumb, or whether water has an analgesic property inherent in itself; and reached the latter conclusion. The addition of even a very small proportion of any one of quite a number of other drugs greatly helps to render more effective this power of water. Before studying these seriatim, let me say that it is well for the general practitioner, occasionally called upon to do some major operation in emergency, to remember that without rendering the patient unconscious, and by the use of simple means readily at hand, a very fair degree of success in blunting pain may be attained. The writer well recollects assisting Dr. John A. Wyeth twenty-five years ago, in ampu- tating a en; ii,, I arm at the shoulder-joint. The pat ient . a middle-age< l.m inesl hesia. Instead he drank nearly a tumblerful oi .and received by needle nearly a half grain of morphine. lie was maudlin and cheerful throughout; hi showed no suffering— and he had no -hock sub- equently, making a good recovery. Ucohol u ed in this way v, a eery of major ane the ia. I.oc.-d applications of the volatile oih are among the best known and oldest mean- of benumbii suffering nerve. Each and everj volatile oil possi analgesic qualities, but some surpass other- in this ,1. Oil of cloves, for example, applied within the cavity of an aching tooth, upon a bit oi cotton, usually gives prompt relief, 'linger for intestinal colic — dependent for effect upon it- oil is as well- known an instance. Menthol in say ten per cent. solution in alcohol gives much relief in tteur uffering, alike from the analgesic power of its volatile oil and because of vigorous eounterirrita- tion. Of course sundry other instances of this gen- eral principle could be adduced. Chief in importance among drugs for local anesthesia is cocaine, usually in the form of the hydrochlorate. It may now be obtained in both the natural and synthetic forms. It is soluble in 0.4 parts water at 77° F. Except in very strong watery solution it has no antiseptic power, and in any strength ordinarily used it quickly develops fungus, rendering it irritant and unfit for use. Therefore, it is best to make a fresh solution each time it is to be employed, al- though a saturated solution of boric acid in water will keep it quite well for an indefinite period. Boil- ing decomposes it into ecgonine and other alkaloids all of which have some little anesthetic power, 1 nit much less than the undecomposed cocaine. A simple and reliable plan of making readily one's solutions of it afresh is as follows: Boil in a test-tube say 100 minims of water; remove from the flame, and the instant ebullition ceases the temperature will be fractionally lower than the boiling-point. Instantly drop in a hypodermic tablet of gr. J, if a half per cent, solution be required, and so on. These tabids are made by all responsible dealers in a most careful and cleanly way, to avoid a bad reputation for hypodermic abscesses from their goods, and the heat is still enough within the boiled water, if used instantly as stated, to render safely sterile such tablets in this solution. Cocaine is unquestionably the most anesthetic of known remedies for use in this manner, but it is likewise the most dangerous; first from acute poisoning from an overdose, and second because of the great risk of inducing a habit hard to be overcome and ruinous to the health, if its adminisaration is repeated more than a few times. The smallest fatal dose, with sound organs, seems to be about one grain, in the adult, though much more than this has often been absorbed without trouble, particularly when injected in highly diluted solution. One of the most striking character- istics of cocaine activity, and in which it differs from almost all the other anesthetic remedies intended for hypodermic usage, is its power to cause vigorous con- traction of blood-vessels. For instance, given an acute coryza, the patient being wholly unable to breathe through the nostrils because of mechanical obstruction of the nasal air-passages from great congestion of the mucous membrane and turbinate bodies; if the interior of a nose so affected be sprayed with a cocaine solution, within a few minutes a mu- cous pallor will have replaced the angr}- redness, and the breathing through the nose will have become quite free. And yet this would be a very objec- tionable mode of treatment, for within a half hour or so the congestion would return — indeed, worse than ever, because of the violence done the nerve- mechanism of the vessels. Also perhaps the chief 387 Anesthesia, Local REFERENCE HANDBOOK OF THE MEDICAL SCIENCES way in which the cocaine habit has been started is by the employment of weak cocaine snuffs and solu- tions intranasally in futile attempts, commonly by advertising quacks, to cure catarrhal conditions. There are a few instances, however, in which this contractile power of cocaine may be used wisely and with advantage to the patient. Especially is this true of complete urinary retention due to a temporary congested or inflammatory stricture superadded to a more or less tight-calibered true or organic one. Here filiform bougies as well as the smallest soft catheters having failed to gain entrance to the bladder, the intraurethral injection of a one- or two-per-cent. cocaine solution, held for some minutes pressed backward against the obstructed region, quite regu- larly results in permitting, for a few minutes, as free emptying of the bladder as before the congestive trouble was acquired; and a small catheter or fil- iforms can be passed, painlessly too, to be temporarily retained after the congestion returns. Injection of adrenalin in solution would do the same thing, but without the anesthetic effect also resultant from the cocaine. We have dwelt upon this power of cocaine over blood-vessel caliber chiefly to emphasize its responsi- bility for most of the dangerous symptoms consequent upon cocaine poisoning from overdosage. Contrac- tion of the blood-vessels everywhere in the brain doubtless results, but the danger is chiefly because of this effect upon those vessels at the base of the brain, and hence supplying blood to the respiratory center. Death occurs, if at all, from failure of respiration — save in cases where the heart is not normal. The patient becomes pale, breaks out into a cold per- spiration, often is nauseated, complains of dizziness, is seen to breathe with some difficulty and irregularity, and has a rapid — sometimes a slow — and feeble pulse. Convulsions sometimes precede coma. The treatment consists in the use of stimulants, vasodi- lators, and a good sized hypodermic injection of morphine. Why the latter should be so valuable — as it unquestionably is — the writer does not know; for morphine is not a vasodilator. Trinitrin by needle and amyl nitrite by inhalation are of value as such dilators, also atropine as a direct respiratory stimulant. Artificial respiration is of course indicated when breathing fails; but both in prevention and in treatment one may safely rely largely upon the free use of alcohol, remembering alike its stimulant effect and its striking power in full doses to dilate blood-vessels, especially of the brain and face. The writer never fails to give a drink of whiskey — unless there is some moral scruple — prior to using cocaine in surgery, and attributes to this measure of pre- vention, as well as caution in dosage, his never having personally had to deal with really serious symptoms from this drug. While upon this phase of the subject it is well to call attention to the seeming contradiction between the weak dosage at present almost always used in cocaine hypodermic injection, and the concentration in which it is employed by nasal specialists prepara- tory to cutting or sawing work within the nose. Twenty-per-cent. strength is an every-day matter, and some such operators prefer to apply — as being safer — cocaine hydrochloride in powder form, undi- luted, to the mucous membrane about to be operated upon. The explanation is found in this extreme contractile power of the drug over vessels; and the greater the concentration the more striking and almost instantaneous is this effect, the blood-vessels being reduced to the merest threads, and the mucous parts to the most extreme pallor. In consequence this poison cannot be absorbed and carried into the general circulation. In ordinary local analgesic usage — in preparation for operation elsewhere than within the nose — the writer seldom employs a strength greater than one-half per cent, in the skin, and one-fourth per cent, in the deeper tissues. Indeed it is often used far more dilute even t han this. One part in a thousand of water or of nor- mal saline solution is not rare when we wish to diffuse the anesthetic effect over a large area, and one to five or even ten thousand is a proportion employed by some surgeons. The only objection to such a large bulk of injected fluid is the distortion of normal relationships, anatomically speaking, and at times this is not a triv- ial objection. Schleich, who was first to point out the value of cocaine in such high dilution, has, for hypodermic injection, prepared after considerable experimenta- tion the following solutions, known respectively as the strong, the normal (for average use) and the weak: Sol. I. Cocalni hydrochlorici 0.2 Morphinse hydrochlorici 0.025 Natr. chloral, sterilisat 0.2 Aquas destill. sterilisat ]ad 100.0 Addeacid. carbol. (5 per cent.) gtt. 2 Sol. II. 0.1 0.025 0.2 100.0 Ktt. 2 Sol. III. 0.01 0.005 0.2 100.0 gtt. 2 It must be noted that to accomplish a painless cutting of the skin the drug, in whatever degree of solution, must be in- u %&p ^%< pv. jected into, not beneath, the skin. Beginners in surgery commonly do not do this in such way as to give a max mum of prompt anesthe- sia with a minimum of prior annoyance. It is now well recog- nized that Schleich was in error in adding mor- phine to his solutions for local anesthesia. So far from being an advantage, the morphine has no local anesthetic properties whatever. Indeed, it is to a very slight degree an irritant, and has a tendency to cause a troublesome after-edema of the tissues. It is well, however, to dilute the cocaine solution for in- fill ration work with a little chloride of sodium. About three-quarters of one per cent, of it makes a satisfactorily isotonic solution; and, particu- larly in dealing with in- flamed or highly sensi- tive tissues, this is dis- tinctly more soothing than dissolving the co- caine or other analgesic agent in plain sterile water. As in inexperienced hands the method by edematization (infiltra- tion) is apt to give un- satisfactory results, be- cause not thoroughly done, it may be well to give Schleich's own vivid description: "The infiltrated area must project high over the normal level of the surrounding tissues, taking the form of &s0 Fia. 230. — Showing Injection Along a Line of Incision in Skin. X, X 1 , X 2 , etc., first, second, third, etc., points of injection. After the first puncture, A, the needle is always inserted in the edge of the area last anesthetized. (From Schleich.) 388 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, Local si. edematous, broad-based sessile tumor. On in- cision the tissues should have a glassy or jelly-like appearance, the tissue fibrils being spread out, and ii„. mi surface weeping like that of a cucumber or an over-ripe melon. An infiltrated penis, lip, <>r ear lobule musl appear as it affected with elephantiasis, and pendulous tumors such as hemorrhoids, fibromas, sarcomas, become often ten times their former size. The >kia over such tissues becomes like silky papi r and almost transparent like glass. The tough, elastic cutis vera naturally opposes considerable tance to this distention, but even with it a ienl edema is much more intense than that i in any pathological conditions." In a word, the tissues musl be distended to their utmost to produce sal isfactory anesthesia by this, the in lilt rat ion method. The writer prefers, for infiltration, toanyoi i he t hive Schleich formula' those of Struthers,. which follow, and particularly No. •"■. No. 1. Cocaine hydrochloride 1 grain. Solution of adrenalin chloride ' 1 in loom . . . 12 drops. Solution of sodium chloride (0.75 percent.).. 2 ounces. No. 2. Eucaine lactate 1 grain. Solution of adrenalin chloride I in 1000).... 5 drops. Solution of sodium chloride (0.75 percent.).. 10 drams. No. 3. Cocaine hydrochloride 1 grain. Eucaine lactate 1 grain. Solution of adrenalin chloride (1 in 10001 .... 12 drops. Si lution of sodium chloride 10.75 per cent.).. 3 ounces. The syringe and needles, as also the glass measure for preparing solutions, must be sterilized in plain water or saline solution, but not in soda solution, for soda breaks up the cocaine or eucaine and destroys their analgesic properties. The needle — always small in caliber and very sharp — is passed into the skin at a first point proximal to the region inflamed, or to any region requiring cutting. The injection of some drops into the skin, ju.st beneath the cuticle, almost instantly produces a roundish very pallid area called a "wheal." Into this wheal the needle may now be advanced without sensation of discomfort resulting, and at its farther border a further wheal is produced in the same way. Thus continue until a pallid and insensitive area is produced as far as the knife is to reach. Beneath to benumb the more effectually the operative area sup- plied by the nerve in question n is always to b o injected at a point well proximal to the field of its operative nerve supply), and b) b a means of trying to prevent shock, received through the sensory, hence afferent, fibers of the nen nerves in question, about to be divided at operation. If at some proximal level nerve blocking can l>e accomplished, then the blow of a major operation cannot for the time being be conveyed to the vasotonic or shock center in the brain. The trouble is that within an hour Ol pp ' operationem the effects of cocaine nerve blocking pass ofi as the drug is taken up in the genera] cir- culation and the shock is only postponed for this brief period. An agent capable of maintaining such nerve blocking for a day or longer is s -tiling still to be searched for. Quinine and urea-hydrochlorate nen e blocking — to be discussed later on — gives promise of this. Fig. 231. — Showing Injection Below Abscess Near Surface of the Skin. X, X, points of injection. (From Schleich.) this area infiltration may be used as desired. Let it be noted, however, that whenever in process of cut- ting any blood-vessel or sensory nerve is exposed, such will probably require a special additional injection to prevent pain before section. Blood- vessels are unquestionably more sensitive to pain than most other structures except sensory nerves. "Nerve blocking" is a name used to cover the em- ployment of a special technique for either of two pur- poses. It implies the injection directly into a nerve containing sensory fibers of a rather stronger cocaine solution than that used for any infiltration, thereby (a) Fig. 232. — Showing Injection Around a Tumor (in this case a ganglion) with Curved Needle. G, (ianglion; N. skin; T, tendon and sheath; a, 6, c, etc., first, second, third, etc., points of in- jection. (From Schleich.) It is worthy of careful note that cocaine anesthesia is invariably distal from the point of nerve blocking. For example, if into the ulnar nerve behind the inner condyle at the elbow cocaine is injected in effective strength — a few drops will suffice — within a few min- utes we can amputate the little finger painlessly. But if we expose this nerve at any level even in the least proximal from the point so blocked, it will be found just as sensitive as ever. This explains the otherwise rather surprising ineffectiveness of cocaine solutions, even the strongest, conveyed into the cavity of a tooth, to attempt thereby obtunding pain when the dentist resumes his excavating. Only the surfaces of the tiny nerve fibrils within the dentine actually exposed are in the least. affected. The first few strokes of his sharp bone cutting implement remove this surface, and as the anesthesia from cocaine never travels backward toward the brain, but only distally, the pain is presently as bad as before. The writer many years ago before the New York Institute of Stomatology described, as a result of his experiments, methods whereby, during extracting or excavating, cocaine can be introduced so as effectually to block the pain-bearing power of the dental nerves, both upper and lower. For the four upper incisors, take a thin pad of absorbent cotton, saturated with a cocaine solution varying from two per cent, to a little stronger, and E, Abscess; 3S9 Anesthesia, Local REFERENCE HANDBOOK OF THE MEDICAL SCIENCES pack this with the little finger end, or a narrow spatula, upon the floor of the nose, at the front. Within ten minutes as a rule the insensibility is readily observable in these four teeth. It is well known that from the second bicuspid to the last molar the roots of the teeth are close in con- tact with the floor of the antrum of Highmore. Now by injecting a cocaine solution into this antrum through its natural opening in the outer wall of the nose — middle meatus — in a few minutes benumbing follows. Where the opening is not readily found, with a stout, short hypodermic needle a passage can, by a single light tap, be forced through the extremely thin bone constituting the front wall of the sinus — just above the roots of the first molar teeth, by choice — and thus injection into the antrum accomplished. As to the teeth in the lower jaw, all those behind the mental foramen can be reached by obtunding the inferior dental nerve by aid of a very long hypoder- mic needle passed through the cheek at right angles, through the sigmoid notch of the mandible just below the zygomatic arch. Of course more space for the ready accomplishment of this step will be gained if meanwhile the lower jaw be held apart from its fellow. As to the front teeth, injection directly into the mental foramen, to be found directly beneath the second bicuspid tooth, will satisfactorily prepare them for work. It is nowadays quite customary for dentists to extract painlessly, and in dealing with certain very sensitive patients, to excavate without causing suffering, by use of cocaine solutions — or of eucaine /J or of novocain — combined, for the longer effect, with a little adrenalin, and injecting this directly into or in contact with the nerves about to enter the roots of the teeth, by aid of very slender hypodermic needles of platinum, and permitting of bending to any desired curve without breaking. It is worth mentioning that cocaine is undesirable for use as a means of relieving inflammation by its application, however dilute. Dr. Carl Koller, who is the discoverer of the anesthetic power of this drug, has pointed out that in ophthalmia for instance, the prolonged use of such solution as a soothing agent for the local pain may result in superficial ulcers of the cornea. To Dr. J. Leonard Corning we owe the first demon- stration of the means whereby in operating upon any extremity, now, we are enabled to hold the cocaine solution in place until we can at our leisure complete the operation, instead of, as formerly, having to inject again and again, the circulation sweeping away our anesthetic agent and the anesthesia there- with. This is the simple device of cording proxi- mally to the operative field. In freezing, be it remembered that if we cord at all we do it first, and then freeze. The reverse should be the case when employing any drug by hypodermic means preparatory to cutting; for here we inject first and immediately afterward cord. During the fraction of a minute intervening between the injection and the cording the circulation will convey our chemical to tissues round about the points of injection; whereas had we first corded, then injected, the solution would lie in the track of the needle or thereabouts and anesthesia would be less satisfactorily accomplished. The addition of a certain amount of adrenalin to the cocaine solution, or indeed to any of the other drugs used likewise in operation, materially helps us in regions where cording is impossible, |,%- producing a strong degree of local anemia not obtainable by the weaker proportions of cocaine and not obtainable at all otherwise by almost all of the other local anesthetics. Indeed, hi one sense the adrenalin may be said, in operations upon head, neck, and trunk, to take the place of cording elsewhere, in that it effectually holds the analgesic agent in place where it is needed. It may here be noted that the addition of a'ntipy- rine to a cocaine solution prolongs very noticeably its anesthetic effects. The strength of the antipyrine may be as high as four per cent., but in this proportion it smarts somewhat. If only one to two per cent, be employed this objection is not observable when it is combined with cocaine. Cocaine is freely absorbed from a mucous surface but not from the skin. This explains why it is useless, in whatever concentration of solution, when intro- duced within the external auditory meatus for the relief of earache, or prior to cutting the ear drum which is covered with skin, not with mucous membrane. Tropacocaine Hydrochloride. — This is obtainable both from the small-leaved coca plant of Java, and by synthesis. It is quite expensive, compared with cocaine, and is relatively much weaker. It has chiefly been used in spinal analgesia up to the present time. The writer has thus employed it in his service at the City Hospital (New York City) in over 500 instances without death or serious symptoms resulting. He has regularly used for this purpose gr. ij. dissolved in normal saline solution 5j. and finds that this can usually be relied upon to produce within ten minutes or less a perfectly satisfactory analgesia lasting upon the average one hour. And this is devoid also of the nausea and vomiting so frequently attendant upon the early stages of spinal analgesia produced by the use of cocaine solutions. The only drawback is the occasional severe headache following and sometimes lasting a day or even longer; but this objection seems to attend the employment of other spinal analgesics, an ideal one of which has not yet in this single respect been found. Very large doses of phenacetin, repeated, are perhaps as good a way as any of treating such headaches. Tropacocaine is freely soluble in water, keeps well in solution, and is not decomposed by boiling. Novocain is soluble in one part of water. May be boiled without decomposition, and its solution keeps well. It is a local anesthetic of much value, and far less toxic than is cocaine. Its effect is greatly enhanced by the addition of adrenalin to the solution; and numerous firms now prepare tablets combining these agents in various proportions. Novocain itself 1 as no contractile power over blood-vessels. This drug, in the combination mentioned, is being much more used of late, and the reports are uniformly favorable. It is employed in from one-half or two-per-cent. strength usually, but has been used even in twenty per cent. It has been absorbed up to gr. vij. or viij. with- out trouble, so feeble is its toxicity. Tablets contain- ing gr. J novocain and gr. ■*%■$ synthetic supra- renin are obtainable on I he market andareineverj way satisfactory. One such tablet in oj. of sterile water makes a solution of slightly more than 0.5-per-cent. strength, and is amply sufficient for ordinary opera- tions upon skin and muscular tissues. Less than this strength suffices for work upon mucous membrane and the tissues just beneath it. Eucaine beta, and lactate of eucaine, which latter is more freely soluble in water, is a most excellent drug for producing anesthetic solutions for local use. It is practically devoid of poisonous properties. Thirty grains have been injected and absorbed without pro- ducing toxic symptoms (Kiessel). It is somewhat less anesthetic in power than is cocaine, weight for weight, but this objection is easily overcome by using it in stronger solutions than the latter. It is slower in developing its analgesic effect than is cocaine. Two per cent, is perhaps an average strength, and it stands boiling well, and keeps well. The addition of adrenalin to its solution is of distinct advantage in maintaining and prolonging the analgesic effect. By itself eucaine has no power to contract blood- vessels, even perhaps somewhat dilating them, rather. 390 REFERENi E HAXDHOOK OF TIIF. MEDICAL S< II Si ES LnesthesUt! Local Pennington recommends the following R Boil. Beta-eucaine lactate sr. iij. Sodium chloride. . gi Bolu "i Buprarenal chloride, full strength, tljx. ed water o,. s. ad ?,. Tor hypodennio use. In as great strength as five per cent, the writer cannot commend eucaine beta for local anesl because in this percentage injected beneath the fore- skin in a case of circumcision it caused sloughing of the skin. and Quinine Hydrochloride. — In this com- ition we have a very old and reliable means of treating ugly types of malarial infection successfully, in doses of gr. xv and more of the quinine by hypo- dermic. To the writer's knowledge, here in New York. Dr. \Y. II. Thomson (who is believed to have originated the thought) and other eminent physicians more than thirty years ago used this plan. And they recognized and spoke of the striking degree of local anesthesia which resulted. It will ever be a source of wonderment to the writer that nobody "put two and two together" and thought of making use of this benumbing as a means of avoiding the agony of tin- knife. It was long years afterward before cocaine anesthesia was proclaimed to the world, and in the interval, as before then, we used to put our pan of necessity, as far under major anesthetic uncon- sciousness to remove a sliver or cinder from the cornea as to amputate a thigh. Only within the past very few years has analgesia from this source been recognized as of practical surgical value. Tablets of various strengths arc now upon the market. These are freely soluble in water, and stand boiling well; but, as with cocaine. a fungus or mould forns if allowed to remain long in solution after exposure to the air. An ordinary tablet is one containing urea and quinine hydrochloride gr. ss. This is dissolved in 5i. of water, and though often used stronger, for it is not poisonous in any dosage, it is somewhat irritant in increasing strengths of solution. Indeed, because of such irritant property it is not advised usually for local anesthesia where one hopes and expects to obtain healing by primary union. The surprising thing about the employment of this anesthetic, wherein chiefly it differs from any and all others for local employment by hypodermic is the la( anesthesia; but 200 hours is not surprising, although not always obtainable. By reference tn the earlier remarks ("under heading of Cocaine) upon Nerve Blocking against Shock, it will be readily seen how much more likely is so la-ting an effect upon the afferent nerve fibers to prove essful and life saving than any anesthetic the effects of which are gone within an hour or a very few hours at longest. ',' I lie. — This drug, soluble in eight ami one-half pans water, is sometimes used alone (without the combination with urea), and is eff( in two per cent, solution. Dr. B. 1). Sheedy of New York uses it upon adults thus, prior to tonsillectomy. In five per cent, strength we have more bleeding, dis- tinctly, than without its use, and also post-operative inflammatory reaction. This seems evidence of its tendency to irritate, and a greater strength of solu- tion than two per cent, is not advocated. It is prompt in producing its analgesic effect, and is of course practically devoid of danger of systemic poisoning in any desired dosage. Stovaine H ydrochlorate. — This is a synthetic prod- uct, freely soluble in water. Is an "effective local anesthetic, but dilates the blood-vessels — the more reason for combining it in solution with adrenalin. It rather tends to stimulate the heart action, and is only from one-third to one-half as toxic as cocaine. The dosage varies from three-quarters of one per cent, which is usual for hypodermic use, up to five or ten per cent, when employed upon mucous membranes chiefly. It has largely, perhaps mainly, been advocated in spinal analgesia, and Jonnesco has strongly advocated its employment thus, combined with a small per- centage of strychnine, which he claims adds to its benumbing power. Holocaine. H ydrochlorate.— This is soluble in fifty parts of water. It has an even quicker anesthetic effect than cocaine, and its solutions in water keep well, as it is strongly bactericidal. It is, however, more toxic than cocaine. A oue-per-cent. solution has just about the same analgesic power as cocaine (Wharton). Because of its more poisonous properties it is used chiefly upon mucous membranes, especially the conjunctiva. It has no effect upon the size of the pupil. Alypin. — This occurs in a white crystalline powder, extremely soluble in water — even hygroscopic. Its solutions may be sterilized by boiling for not longer than five minutes. Locally applied to the eye it causes congestion of the blood-vessels, but no myd- riasis nor disturbance of the accommodation. It is less toxic than cocaine, but about equal to it in local anesthetic power. Is used upon the mucous mem- branes in ten-per-cent. solution. For hypodermic injection a one- to four-per-cent. strength may be employed. Not more than gr. ij. should be absorbed at one time. It has largely been employed in spinal analgesia, chiefly in Germany. Orthoform (new). — This occurs as a fine, white, taste- less and odorless, crystalline powder, moderately solu- ble in water. Is decomposed by boiling water. Is a local anesthetic of much power and value but acts only upon mucous or broken or ulcerated surfaces. It is somewhat antiseptic, and is practically devoid of poisonous properties. It is used as an antiseptic and to relieve the pain of burns, wounds, ulcers, excoriations, etc. The writer can strongly commend it, having for years 391 Anesthesia, Local REFERENCE HANDBOOK OF THE MEDICAL SCIENCES applied it to newly operated rectal and intranasal surfaces, in ten- to twenty-pcr-cent. strength rubbed on with vaseline, also as a dusting powder to painful ulcerations. Its analgesic power is longer main- tained, as compared with all other local anesthetics, (except quinine and urea hydrochloride) for twenty- four to forty-eight hours after operation, for example. The only difference between the old and new ortho- form is that the latter is more readily soluble in water. Anesthesia. — This occurs as a white, odorless, taste- less, crystalline powder, almost insoluble in cold water. By prolonged boiling is decomposed. Is a local anesthetic similar in effect to cocaine, but without its local irritant action and its toxicity. On account of its insolubility its anesthetic effect is only super- ficial, but is more prolonged than that of cocaine. Xcrrociilhic. — This is the hydrochloride of an alka- loid derived from gasu-basu, an Indian plant. It occurs as a yellow hygroscopic powder, readily soluble in water. It is used ehieflj' in dentistry as a local anesthetic, in a 0.1-per-cent. solution; upon the eye, in 0.01-per-cent. strength. Brenzcain (guaiacol benzyl ester). — This occurs as white crystals, insoluble in water. Is said to possess the advantages of guaiacol without its irritant, action, and is used in the same manner as the other guaiacol preparations. Its chief value is in producing anesthe- sia locally by aid of cataphoresis. Phenol (carbolic acid). — A deliquescent white powder, its solutions becoming pink and subsequently dark red upon prolonged exposure to light. Soluble in water, when deliquesced, to the extent of five per cent. Is studied under the present heading only because of its quite striking benumbing qualities. In watery solution of from two up to five per cent., it soon obtunds local sensibility of skin or mucous surfaces, but is too poisonous for safe usage beneath the skin in this manner. Application of alcohol, if promptly employed, neutralizes its poisonous effects. Not more than gr. j.-ij. should be absorbed at one time. Pantopon. — This is a reddish powder, a mixture of all the active principles found in opium, in their several relative proportions. Is soluble freely in water, and supplied to the market in ampoules of a clear watery solution, of an average dose each; or else a mixture may be prepared for hypodermic usage of seventy-five per cent, water and twenty-five per cent, glycerin, as to the menstruum. Gr. § is an ordinary dose of the powder; corresponds (about) to gr. J morphine, in strength. It, however, affects tin' respiratory center much less than does morphine, and has not the unpleasant after effects of morphine. It is desirable — but not essential — to combine for hypodermic use with each gr. $ of pantopon gr. j-J^ of scopolamine. The result is very satisfactory. Biirgi has pointed out that whenever two narcotics are injected simultaneously, the effect is more potent than when a dose of one alone, equal in strength to t he combination, is injected. Pantopon is not alone used to relieve local pain, but is a very desirable means of preparing the pal ient for major anesthesia, injected an hour beforehand. Acoin. — This is a white, very bitter powder, soluble in seventeen parts of water. Is very sensitive to alkalies and to light. Is a local anesthetic, employed in one-per-cent. solution. Benzoyl peroxide (or superoxide). — This occurs as permanent, non-deliquescent, white, odorless prisms, slightly soluble in water. Is a mild Ipcal anesthetic, but a strong disinfectant. Is used either pure, in ten-per-cent. ointment, or in a saturated solution in olive oil. Chloretone (chlorbutanol, acetone chloroform) oc- curs as a white, crystalline, volatile compound, having a camphoraceous odor and taste. It is soluble in water. Is a weak local anesthetic, an antiseptic, and a hypnotic similar to chloral. Is used as a mild 392 local anesthetic, in dentistry chiefly; also inwardly to soothe gastric irritability. Dose, gr. v.-xx. Chloral-menthol is produced by triturating equal parts of chloral hydrate and menthol in a mortar and then heating in a water-bath until liquefied. It occurs as a colorless, oily liquid, with a distinct mint-like odor and warm taste. Is used as a local anesthetic and counterirritant, chiefly in treating neuralgia. Cliloral-camphor. — This is a thick, almost colorless liquid, with a strong camphoraceous odor and biting taste. Is the result of prolonged trituration of cam- phor with chloral hydrate in equal proportions. It is botli locally analgesic and counterirritant, and is rather a favorite application to the skin in cases of obdurate tic douloureux. We can strongly commi ,,,[ the following as an improvement upon chloral-cam- phor unmodified. H Camphor 3 ij Chloral hydrate 5 iv Olei betula 1 5 iij Ext. fl. cannabis ind 5 ij Alcohol q. s. ad 5 iij M. S. "Pain paint." Phenol-camphor. — The curious property of camphor wherebyit prevents phenol from causing sloughing, even in equal parts, is worthy of notice. If to these we add glycerin c.p., making a mixture of equal parts each of camphor, phenol, and glycerin, we have a most excellent dressing for an unclean wound — acting as a powerful antiseptic, and also stopping the pain and tenderness which is one of the most striking clinical features distinguishing the course of an infected wound from one, however large, which is aseptic If used in a wound of the latter class the presence alike of carbolic acid and of glycerin will cause the wound to discharge serum freely, and thus necessitate drainage at first. Used upon the skin the camphor-phenol-glycerin combination constitutes a really excellent liniment against the pain of neuritis, rheumatism, etc., and is one of the best antipruritics. Propepsin. — This is a white, tasteless powder, non- crystalline, almost insoluble in water, slightly less poisonous than cocaine. Because of its relative insolubility in water, propaesin is used, like orthoform, upon mucous membranes and on raw surfaces, chiefly. Sodium Bicarbonate. — Ordinary baking soda. This chemical is soluble in water, one part in twelve. It is our main reliance to soothe the suffering attendant upon burns, and fortunately is at, hand where burns are oftenest produced — the kitchen. Saturated in cold water or else applied supersaturated, as a kind of mud, it is very comforting and moderately an- algesic and is to a slight degree antiseptic. Most bi- salts are acid, but this is exceptional, being slightly alkaline in reaction. As another and striking instance of its employ- ment in surgery under our present heading, we may mention that after operating upon a lacerated cervix uteri, or its amputation, numerous operators adopt the custom of packing the upper portion of the vagina with sodium bicarbonate in order that there may be no after-pain or tenderness. By whatever drug the surgeon decides to produce local anesthesia, the following sensible statement (Struthers) should be borne in mind. It is well not to pinch or prick the skin over the injection-area and ask the patient if pain is felt. A certain amount of tactile sensibility is nearly always retained; and patients are apt, when nervous, to misinterpret their sensations and in reply mislead the operator. If the injections have been properly made, the skin will be absolutely analgesic, though not anesthetic. It is a good rule after waiting the necessary time, to cover the patient's face with a handkerchief or towel to pre- vent a view of the operation, and to proceed with the REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anesthesia, Local incision at once without asking any questions, it is :l good working rule to ask no questions as to pain during operation, in order to avoid any suggestion tli-it one is uncertain of the power of the drug to pre- vent pain. Should real pain be felt, the patient may safely be trusted to intimate it by word or gesture, without being asked. Venous Local Anesthesia. — This method, an ex- cellent and successful one, was first advocated publicly by Bier of Berlin, in 1908. The technique follows, modified by reversing the order of pr tdure; it seeming to the writer self-evident that the exposure of the vein should first be done while full of blood, and hence easily found; and that thru the double constriction of the limb should follow this step. Any large superficial vein is to be exposed by dis- ion: the internal saphenous, not far from the level of the knee, in cases where excision of this joint is templated, for instance. Next apply a stout rubber bandage as in the Esmarch method of obtain- ing anemia, carrying this to a point well above the region of operation. Undo it from below, leaving it, shutting off all blood supply at the highest (most proximal) level. By a second rubber bandage we constrict the limb tightly at a level away from — distal to — the region operation. We now have an entirely anemic interval of limb varying from a few inches in vertical ut to much more, according to cutting-room led. In the middle of this space lies the exposed and of course empty vein referred to. This is next cut," obliquely, partly across — enough to receive the nozzle of an ordinary saline-infusion cannula; and this is tied in securely. The anesthetic in somtion (to be farther mentioned later on) is now injected by aid of a sterile syringe. Bier thinks it of small importance whether the fluid lie injected proximally or distally; if anything, he rather inclines to prefer the latter; which of course means that under steady and firm pressure all the veins in this region will have their valves overcome, so that within a few minutes all the interval between the two bandages will have become analgesic. Bier prefers a half of one per cent, of novocain dissolved in physiological salt solution. For exci- sion of a knee he injects of this lin-SO c.c; for excision of an elbow, 40-50 c.c. — and so on. The cutting being completed, before suturing he desires to get rid of some of the chemical rather than to have it all absorbed. For this purpose he first entirely removes the lower — distal — rubber bandage, and then loosens the proximal one enough to permit general congestion of the limb below, and some bleeding from the arterioles; removing the constric- tion entirely when he judges that enough novocain has been thus washed out. However, novocain is certainly among the safer of the newer anesthetics; it is far less poisonous than is cocaine, for example. Light. — The local anesthetic effect of light is one of the most striking of those produced by exposure of the body to the actinic end of the spectrum — the violet and ultra-violet rays, chiefly, being responsible therefor. This is best accomplished by the use of the Minin light (A. W. Minin, at present Surgeon- General of the Russian Army). This lamp, aided by a parabolic reflector, for concentration, conveys the violet rays phis those just beyond and faintly but distinctly visible against a white background. The "step-off" rays, as Douglas H. Stewart ap- propriately terms these last; and he names the color of the Minin bulb "royal purple." .Minin affirms that the therapeutic value of his lamp is perhaps even greater in treating surgical injuries and conditions than in handling internal diseases. As to the former, the analgesic power is strikingly manifested, permitting operation, suturing, etc., to be performed painlessly after some ten minutes or so of exposure. The al ption of subcutaneous and interstitial hemorrhages and also of inflammatory exudates is quite readily accomplished. As to the analgesic relief of non-surgical afflictic the power of tin- IilIiI i- also remarkable; for ex- ample, nil pains from pleuri y, from articular rheuma- tism, from cutaneous inflammation and that of the deeper cellular tissue di appear entirely after a single thorough treatment, or reappeai greatly di- minished after a longer or shorter interval of time. He says that it is true that neuralgias make an ex- ception to this claim of benefit, and that pains of this nature may even become aggravated following the first seance; but that after the second sitting a dis- tinct improvement can usually be noticed. The writer, in neuralgia due to neuritis and peri- neuritis — obstinate sciatica of this nature, for a striking example — has upon tl ther hand repeat- edly observed the most rapid and really wonderful relief from tin' u-e of the Minin light; and it would seem that we should distinguish, as to its value, between neuralgia due to inflammatory action anil neuralgia not a neuritis but most commonly die to anemia — or as Romberg phrased it, " a prayer of the nerves for more red blood" — and hence best treated by hematinics, especially chalybeates. Although the Minin royal-purple bulb is preferable, yet it is well worth knowing that by use of the or- dinary sixteen candle-power Edison incandescent bulb of colorless glass we can produce a fairly good analgesia locally in the course of from twenty minutes to a half-hour's exposure; and that this is indeed a better degree of analgesia than is obtainable by use of any blue-glass bulb upon the market. These latter crcen out the violet, the ''step-off," and ultra- violet rays — the power of which is by no means lost to use with the Edison light, which contains all the ray- of ordinary sunlight except the ultra-violet. The glass of the Edison bulb screens these out, unfortunately. There is one striking difference readily noticeable between the activit3 r of the royal purple lamp and the Edison, namely, that the former contracts blood- vessels and thus depletes a granulating surface of its blood, whereas the white light congests it. The local analgesic effect of light, as just discussed, is not in any way due to its accompanying heat. Indeed, it acts best when held far enough away to avoid discomfort from the increased temperature. Furthermore, under analgesia by light, healing by primary union is promoted and aided — a thing which cannot be said of infiltration anesthesia by any drug, though some of them do no harm. Electric Phoresis. — This term is applied to the passage by a galvanic current of crystalline sub- stances in solution through the skin and indeed even through the entire thickness of a limb or the body. By this device local anesthesia may be produced, although it is of more value as a means of relieving deep-seated pain than as a practical surgical agent — both because of the expense and the time involved. Non-colloid (i.e. crystalline) chemicals may be divisible for the purpose under discussion into those electro- positive and those electro-negative. Cocaine is electro-positive for example. Cocaine hydrochlride is applied in concentrated solution (twenty-per-cent. strength in water, for instance) to the positive pole (anode). The current being turned on, and the negative pole (cathode) being placed upon any in- different spot — say upon the opposite side of the limb — and the acid will remain at the positive pole while the active base goes to the negative ditto. This is called cataphoresis. If upon the contrary we wish to administer for some different purpose an electro-negative remedy — ■ for example, arsenic in the form of arsenite of potassium — this, in concentrated solution, should be 393 Anesthesia, Local REFERENCE HANDBOOK OF THE MEDICAL SCIENCES placed upon the negative pole, the other pole being as before placed at any indifferent point, and with the electric action the arsenic as arsenous acid goes to the positive pole, while the potassium — the base — re- mains at the negative pole (anaphoresis) . For local anesthesia by cataphoresis, begin by re- moving the natural oil from the skin by washing with ether or benzene. Then apply upon an electrode, in solution, as just described, cocaine muriate, or aconi- tine, or helleborin, or menthol. An alcoholic solu- tion may be employed where the drug to be used is more freely soluble in this than in water. Chloro- form dissolved in water is sometimes used where both a local analgesic and a counterirritant action are desired. Electrification. — Sinusoidal alternating electric currents of sufficiently high frequency, and in which the positive and negative phases are nearly equal, possess the power of producing local anesthesia. After the frequency has reached 5,000 complete alternations per second the muscular contraction so familiar with medical batteries and other alternating currents decreases, and at 25,000 alternations per second a current passing from the elbow to the hand completely deadens that portion of the limb, and needles may be passed through the flesh without being felt. When subjected to currents of such high frequency the sensory nerves appear to lose the power of transmitting sensations. The sinusoidal current is often anesthetic when all other currents are not. Dourner and Oudin believe that the anesthesia described by d' Arson val (a sinusoidal current), and recommended by him for surgical operations, is the first stage toward cell-death which is quite analogous to the anesthesia caused by freezing. Vibratory Massage. — There are numerous ma- chines upon the market, mostly driven by electricity, for this purpose. It is used for a number of other indications to discusss which would take us afield; but it is worth remembering that vibratory massage is often effectual, and quite promptly so in relief of the local pain and tenderness of nerra'gia, and of sub- acute and chronic rheumatism. The effective dosage must be learned by individual experience. Robert H. M. Dawbaen. Anesthesia, Spinal. — Spinal anesthesia, sometimes called subarachnoid, medullary, or lumbar anesthesia, is insensibility to pain produced by the injection of an analgesic substance into the arachnoid cavity of the spinal cord. The process was first demonstrated by Dr. J. Leonard Corning, of New York, in 1885, and since that date, this method of inducing anes- thesia has been carefully elaborated, and has been practised in thousands of recorded cases by numerous observers both in America and in Europe, where it is much more popular than it is in this country. A large number of drugs, capable of causing loss of sensation by contact with the unsheathed roots of the spinal nerves, have been used for this purpose, prin- cipally, cocaine, stovaine, tropacocaine, novocaine, eucaine, nirvanin, alypin, morphine, antipyrine, mag- nesium sulphate, etc. In the early history of spinal anesthesia, cocaine was almost exclusively employed, but, on account of its admitted dangers, its use has been practically abandoned and it has been super- seded by other substances which are closely allied to it, both chemically and therapeutically, but which have proven far less toxic and consequently less dangerous. Of these preparations, stovaine, tropa- cocaine and novocain, especially the first two and, perhaps, in the order named, are used much more than any other representatives of this class. Tin' usual dose of cocaine for a robust adult — male or female — is 0.02 to 0.03 (i to J gr.) dissolved in 394 sterile water or in the spinal fluid itself. Smaller doses are recommended for j'oung, very old, or very feeble persons. A two-per-cent. solution is ordi- narily employed — a smaller quantity of a stronger solution being generally preferred to an equivalent dose of a weaker solution. Stovaine is readily soluble in water and the so- lution, if desired, may be sterilized by boiling with- out appreciable injury, although some doubt has been expressed on this point. It is a vasodilator, is slightly irritating to the tissues and has very decided effect upon the motor nerves — causing paresis more or less profound. It is this property which pro- vokes distrust in its safety for high anesthesia, on account of the danger of producing paralysis of the respiratory muscles. The usual dose for an adult, either male or female, is 0.03 to 0.06 or 0.1 (J to 1 or 14 gr.) dissolved in 1 c.c. (10 minims) of water, of physiological salt solution, or of the spinal fluid. The dose for a child under five years of age is about 0.01 (J gr.). Fig -Showing the Location of the Spinous Process of the Fourth Luinbar Vertebra. Tropacocaine, like stovaine. is very soluble and the solution may be sterilized by boiling, probably without injurious effect. It is a vasodilator, but it is not irritating to the tissues and it does not affect the motor nerves. The adult dose is 0.03 to 0.06 or 0.1 (J to 1 or li gr.). It may be dissolved in water, in physiological salt solution or in the spinal fluid. Novocain is also soluble in water, in normal salt solution and in the spinal fluid. It, too, may be sterilized by boiling the aqueous solutions, probably without material injury. The motor nerves are only slightly affected bv it. The dose is 0.05 to 0.1 or even 0.15 (} to H or 2\ gr.). Magnesium sulphate exerts a remarkable influence when injected into the subarachnoid space. Lim- ited anesthesia ensues in about forty-five minutes and deep, general anesthesia, with paralysis of the lees and abolition of the tendon reflexes, follows after three or four hours. This state may continue for several hours and, although analgesia may be com- plete, the tactile sense sometimes remains, and the REFEREM I! IIAXnmioK OF THE MEDICAL SCIEN( Anesthesia, Spinal vital reflexes are not disturbed. Under its influi abdominal and pelvic operations and various opera- tions upon the lower extremities have been success- fully performed; ii is, moreover, stated that with a Li ienl « 1 < >—< - . operations upon any pari of the body may be rendered painless. The results of the sub- dural injection of the magnesium salt have not been uniform but, on the contrary, have proved extremely variable and uncertain, and the aftereffects have occasionally been distressing. .V twenty-five-per- cent, thoroughly sterile aqueous solution of a chem- ically pure salt is used. The dose usually recom- ded is 0.02 to 0.03 (J to J gr.) for every two pounds of the patient's weight. Tlie several anesthetic substances which arc com- monly employed — stovaine, troparocaine and QOVO- — are all freely soluble in water, in normal salt solution, and in the spinal fluid withdrawn into the Syringe at the time of the operation. It is claimed that attempts to sterilize these drugs are unneces- sary, as they themselves are antiseptic, and the exact effect upon the activity of the drug caused by boiling the solution is regarded by some as an open question, but the water used as a solvent and the con- tainers should be absolutely sterile. Flo. 234. — Oblique Insertion of the Xeedle for Spinal Anesthesia. Some operators believe that the specific gravity of the anesthetic solution should be greater than that of the spinal fluid. This may be effected, in part, by using a solution not too dilute, or by the addition to the solution of five per cent, of glucose or of dextrine. The advantage claimed for the heavier solution is, that it is not so diffusible as a lighter solution, and that it will not ascend to the upper portions of the canal unless forced up under the influence of gravity by elevating the hips or by- depressing the shoulders of the patient. The heavier solution tends to pool at the most dependent part of the canal and in this manner the height of the anesthesia may be regulated by posture. The addi- tion of adrenalin or of atropine to the injection is ap- proved or rejected according to the individual views of the operator. Strychnine in the solution or the hypo- dermic use of scopolamine and morphine, preced- ing the injection, is regarded as an advantage or as indispensable by some and is declined by others. All agree, however, that the anesthetic solutions should be freshly made — preferably, at the time of the operation. In performing the puncture, the instruments, the hands of the operator and the skin over the back and the loins of the patient should be prepared as carefully as for a major operation. Any of the lum- bar interspaces may be selected for the puncture, but the third or fourth is usually chosen. It has been done as high as the sixth cervical vertebra, but puncture in the cervical region or, indeed, in the dorsal region is considered extra hazardous, and it is generally admitted that under ordinary circumstances, puncture in the lumbar region, even when high anal- gesia is desired, is equally effective and is safest and best. The spinous process of the fourth lumbar vertebra may be located by drawing a transverse line to connect the inn iliac crests; it may then be accurately defined by deep palpation, li"- eat of puncture may be frozen by ethyl chloride or some other local ane thetic n he ski the only sensitive tissue penetrated with the point of a bistoury. The patient should -it upon the of the table or, by preference, lie upon either side, with the body well curved forward. The needle may I Iltered ]US( beneath the spinOUS prOCeSS in the median line and pre! ed firmly a little upward and ard, or it may be entered half an inch to the right or to the left of the median line and passed obliquely toward the spinal canal (] ig. 234). When the point of the needle enter-, the space, which in a well developed adult i- about two ami a half inches below the surface, a sense of diminished resistance will be noticed, ami the spinal fluid will How from the outer end, drop by drop, or in a steady stream. '1 he escape of the fluid is the only conclusive evidi that the cavity has been reached, and if the fluid ! noi appear after the point of the needle is sup- posed to have 'ill. i-'d the -pace, the solution should nol !"• injected, but the needle may be rotated or pushed a little further, a stylet may be passed, tin; patient may cough or make a slight straining effort, or gentle aspiration by means of a syringe may be employed. When the fluid begins to How the finger should be placed over the end of the needle and the syringe containing the warm solution, or the dry anesthetic substance if the spinal fluid is to be used as the solvent, should be attached. Operators of experience disagree as to the advisability of allow- ing a few drops of the spinal fluid to escape before throwing in the solution, some alleging that the nor- mal quantity of the fluid in the cavity should not be disturbed, but that the amount withdrawn should equal or slightly exceed the volume introduced, while others assert that severe headaches and various un- pleasant effects are infrequent if the spinal fluid is not wasted. If a solution is used, after satisfactory assurance as to the position of the needle, the piston should be slowly depressed, but if a powder or a tablet is to be dissolved in the spinal fluid, the piston, already closed, should first be withdrawn, until the barrel containing the anesthetic, with a capacity of 2 c.c. (32 minims), is about half filled with the fluid, which readily dissolves the anesthetic, and then the solution should be gradually returned into the space, the needle removed and the puncture sealed. The patient is then gently laid upon his back with the [dps and the shoulders at such relative elevation as may be appropriate for the desired extension upward, or for the limitation, of the level of the anesthetic zone. The anesthetic effect of a lumbar injection is gen- erally felt in the lower portions of the body in three to five or ten minutes and gradually extends upward coincidently with the upward diffusion, in the spinal fluid, of the anesthetic solution. This diffusion, which is a determining factor in the level of the anesthetic influence, is regulated by gravity, and is controlled by the weight of the anesthetic solution as compared with that of the spinal fluid, and by the posture of the patient. Besides the question of gravity and of the patient's position, the height of the anesthesia — the extent to which it rises — is influenced by the point of insertion and by the quantity of t he anesthetic substance used. The high injection, however, is not necessary to high anesthesia, but a full dose, eleva- tion of the hips and a little more time, may be re- quired for a high effect when the puncture is made in the lumbar region, which is, by all means, the proper place for the injection. The usual duration of spinal anesthesia is from thirty minutes to two hours, and, in some instances, even longer. In testing the pa- tient to ascertain the progress of the anesthesia, it is important to remember that paralysis of the muscles in the anesthetic area does not always occur and that 395 Anesthesia, Spinal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the tactile sense may remain after analgesia has been completely developed. An imperfect anesthesia may follow incomplete penetration of the membranes so that the lumen of the needle is not well within the cavity, thus allowing a portion of the solution, when it is discharged, to be lost in the tissues, or a one-sided anesthesia may result from maintaining the lateral position of the patient, causing the nerve roots of one side only to be bathed in the anesthetic solution. A total absence of anesthesia following an injection is usually due to failure to enter the cavity. It may, however, be caused by inert drugs, by an insufficient dose, or, possibly but not likely, by idiosyncrasy of the individual. In the event of partial or of imperfect anesthesia succeeding the injection, or of insufficient duration of the anesthesia, repetition of the injection or inhalation anesthesia in the discretion of the operator, may be practised, or a combination of the two methods, which is wholly unobjectionable, may be used. Consciousness of the patient under anesthesia, frequently urged as an argument in favor of spinal analgesia may, very rarely, be an advantage, but in the vast majority of cases it is a positive disadvantage. The cooperation, the assent, or the dissent of the patient is seldom required during the progress of an operation, and his knowledge of what is transpiring may result in unfortunate embarrassment to the operator, especially in the presence of an unexpected emergency. The field of the operation should always be screened from the patient's view by some suitable device attached to the operating table, rather than by a mask or by a bandage placed across his eyes. Some enthusiastic supporters of spinal anesthesia attribute to it the power, if promptly invoked, to prevent, to limit, or to arrest surgical shock or shock from severe injuries, and claim for it moreover, bene- fits beyond the range of strictly surgical procedures. It has been used, with varying success, in the treat- ment of tetanus, and it has been employed also, in obstetric practice for the purpose of lessening the pains of parturition. The injection is advised dur- ing the second stage, and it is said that the pain is relieved, while, at the same time, the force of the uterine contractions is not diminished, but that vol- untary effort, on the other hand, is increased— the suffering being absent — so that the duration of the labor is thereby actually decreased. The after-effects of a spinal injection are sometimes more or less severe and protracted, and they may be very serious and really alarming. Among these, are headache, dizziness, mental confusion, inco- herence, fever, delirium, nausea, vomiting, coma, par- esis, retarded or suspended respiration, rigidity of the cervical muscles, pallor, tremor, sweating, incon- tinence of feces, retention of urine, panting, shock, restlessness, cramps, rigors, cyanosis, rapid pulse, subnormal temperature, collapse, etc. Any or several of these symptoms may occur during or after anes- thesia without warning and without obvious reason. The work of Professor Thomas Jonnesco, of Bucha- rest, an ardent advocate and a most daring exponent of spinal anesthesia, lias recently attracted wide attention. The novel points in his method provide, first, that the puncture for high anesthesia — that is, for the arms, thorax, neck, and head — should be made between the first and second dorsal vertebrae, rather than in the lumbar region and, second, that in I lie production of spinal anesthesia, strychnine should invariably be added to the solution of either stovaine, which he prefers, or of tropacocaine or novocain, which he approves — claiming that this precaution averts the danger of respiratory paralysis and fully sustains the circulation. For low anesthesia — that is. below i he diaphragm — the site selected for the punct- ure is the dorsolumbar interspace. Injections at these two sites suffice for all regions, and coverevery portion of the body. After the injection, the patient is changed from a sitting to a dorsal position, with the relative height of the hips and of the shoulders regu- lated according to the desired level of the anes- thesia. The dose, both of the anesthetic employed and of the strychine, should be smaller by one-half to two-thirds in the upper dorsal puncture than in the dorsolumbar puncture, but at either site, whether high or low, the dose should always be adjusted to the age and the general physical condition of the patient, although the variation on this account in the quantity of the strychnine is not relatively great. His usual adult dose, in dorsal puncture, is stovaine, 0.03 (i gr.), strychnine 0.0005 (^ gr.). In the dorsolumbar puncture, stovaine, 0.06 to 0.1 (1 to 1J gr.), strychnine, 0.001 ( T i ¥ gr.). The injection should always consist of 1 c. c. (16 minims) of a freshly made solution of varying strength, within certain limits, in the discretion of the operator. In his practice, age does not seem to bar spinal anesthesia. It is applicable alike to the infant and to the octogenarian. He reports many successful cases ranging from one year and nine months to seventy-five years. The claim that the presence of strychnine in the solution injected obviates the danger of respiratory paralysis is not generally accepted, and the alleged safety of high anesthesia — whether induced by the dorsal or by the lumbar puncture — is stoutly contested and is vigorously denied. Few men of mature judgment regard spinal anesthesia as applicable to all operative cases, but it is generally conceded on the part of surgeons with large practical experience that, while its field is limited, it may be successfully employed when general anesthesia would involve extraordinary risks, as in very old or very feeble persons, in alcoholics or diabetics, or in the subjects of pulmonary, cardiac, renal, or hepatic disease, and that in certain cases and under certain conditions, it may be considered an available substitute for inhalation anesthesia, and as a useful and reasonably safe recourse in operations below the diaphragm, although it has not proved entirely satisfactory or uniformly efficient in abdominal section. Caution should be observed in the application of spinal anesthesia to cases of extreme anemia, asthenia, toxemia, or infection, and if it should be used under these unfavorable circumstances, the ordinary dose should be reduced. James B. Baird. Anethol (C,„H,.,0). — The active constituent of oil of anise, of which it constitutes about ninety per cent., of oil of star anise, which contains somewhat less of it, and of oil of fennel, which contains about sixty per cent, of it. It occurs both as a solid and as a liquid, the former in colorless crystalline plates. Its specific gravity at 25° C. is 0.985." and it melts at 21° to 22° C. It is freely soluble in alcohol and slowly in water. Its odor and taste are purely those of anise, and it may be used with advantage in doses of one to ten grains as a substitute for the above-named oils. H. H. Rusby. Aneurysm, External. — An aneurysm of an artery is a circumscribed tumor composed of a sac, the cavity of which communicates with the lumen of the artery and contains liquid or coagulated blood. The sac may be formed in whole or in part of the distended wall of the artery, or of the condensed adjoining tissues. Definitions and Classification. — The terminol- ogy of the affection has been much confused by a lack of agreement in the use of terms and in the meaning attached to them. Most of these terms are intended to indicate differences in the composition of the wall of the sac, some of which cannot be recognized with certainty on direct examination, and are not marked by any corresponding clinical differences. Internal and External. — Internal aneurysms are 306 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aneurysm! External those situated within the thoracic or abdominal oavity; external aneurysms are those formed at the expense of arteries lying outside these cavities. I \tedical is sometimes used as a synonym of internal; surgical, of external.) Spontaneous and Traumatic. — Spontaneous aneu- rysms are those thai have arisen in consequence ol rjisi ase <>r gradual change in the wall of an artery. A italic aneurj sm is one which has formed in CO [Ce of sudden mechanical ili\i.-i< m or injury of the wall of an artery, as by a knife or splinter of bone. The following anatomical classification, adopted by Holmes, is tlie one in i mon use. The distinc- tion made between "true" and "false" aneurysms is anatomically justified, but the terms an- likely to mislead, for "true" aneurysms, in the narrow sense of the term — i.e. aneurysms whose walls are every- where composed of all the coats of the artery- arc rare and always small. The common form of aneurysm ■ ugs io the class termed "false," those in which on,' of the coals of the artery takes part in the formation of the wall of the sac. I. Common orencysted aneurysm, subdivided into — (a) Aneurysmal dilatation, or fusiform aneurysm. Iln artery is dilated for some distance, and the wall of the dilated portion preserves its three coats. (6) True aneurysm. The sac is formed throughout by all the coats of the artery dilated at only one point. (c) False aneurysm. The sac is formed by only one or two of the coats of the artery, the middle one having disappeared or being unrecognizable in con- BBQuence of change. ( *>*~ it has an epithelial surface ■' ■j^MMjS^itL °f tlat cells and a deeper ! isJ/wBP ^^Sk structure of flat cells sepa- He'^wM ~^» rated by a fibrillary sub- »~ stance. A similar struc- ture is found also upon the surface of thrombi, as after the ligature of an artery, and it must, therefore, be deemed not simply a dis- tended intima, but rather a layer of newly formed tissue. Traces of tlie mid- dle coat may be found at different parts of the aneurysmal sac, especially in the neighborhood of its neck, where, indeed, they may form a continuous layer with that of the artery; but in the more di-teiided portions of the sac they are entirely ab- sent, and it appears to be well established that there is no hyperplasia of the muscular and elastic tissues which compose this coat, but that their elements undergo not only degeneration but also mechanical separation, and they have practi- cally no share in the formation of the wall. The new tissue may itself either undergo fatty degen- eration, or become atheromatous or calcified. As the sac enlarges it may become thinned at some point and burst, with escape of its contents into the adjoining tissues ("ruptured aneurysm"); and when, in its growth, it reaches and presses upon firm, unyielding tissues like bone, the latter undergo absorption. Bone disappears under this pressure by rarefaction that is, a general rarefying osteitis is set up, charac- terized by the enlargement of the vascular canals of the bone, by multiplication of the cellular elements, and by disappearance of the earthy salts, but without production of pus. Other tissues may become in- flamed under the same irritation, and the inflamma- tion may be plastic, with production of adhesions, 397 Fig. 235. — Aneurysm of the Femoral Artery. The walls of the sac consist only of the adven- titia (a) and intima ib) ', the mus- cidaris (c) remains only at the entrance of the sac. (Weber.) Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES or ulcerative. Thus, adjoining serous surfaces unite (pleura, pericardium, peritoneum), or rupture may take place through ulceration of the walls of the trachea or of the esophagus, or of the wall of any other cavity that is pressed upon. These openings may be large or small, and may give rise to repeated small hemorrhages, or may cause death instantly by a free one, either external or internal. The growth of the sac takes place in the direction of least resistance, but this direction is determined rather by the distensibility of the wall itself than by the resistance of the surrounding parts. Thus, the wall may be comparatively firm on the side adjoining a cavity, and growth may be slow in that direction, while at another point where it rests against bone the latter may be rapidly absorbed and even perfo- rated, as is seen in the sternum, and this perforation will be followed by rapid enlargement of the aneu- rysm through the opening. Aneurysms of the limbs seldom rupture through the overlying skin, probably because they receive treatment before their growth has reached such a point; but those of the thoracic aorta and innominate not infrequently end by ulcera- tion of the skin and fatal external hemorrhage. An aortic aneurysm reaches the surface either by growth upward into the neck or through the sternum, or between the ribs to the surface of the chest. The absorption of the bodies of the vertebra; by thoracic or abdominal aneurysms gives rise to some of the most painful symptoms of this fatal and painful affection. In two cases quoted by Mr. Holmes from Dr. Gairdner tin- spontaneous opening of an aneurysm through the skin was followed by the healing of the opening, and in one of them apparently by the cure of the disease; but such a result is so entirely exceptional that it deserves mention only as a surgical curiosity. When an aneurysm has ruptured externally or internally, the progress in the immense majority of cases is from bad to worse if the hemorrhage is not immediately fatal. The bleeding may be arrested by syncope or by the plugging of the orifice by a clot, but it recurs again and again, and ultimately proves fatal, unless the recurrence can be prevented by treatment. The pressure of the growing tumor not only leads to the condensation and absorption of the tissues pressed upon, but it also causes much pain, either by stretching nerves or by provoking a neuritis, and it may inter- fere with the circulation of a part or limb by closing a vein or even an artery, and thus lead to gangrene. The blood contained within an aneurysm is usually in part liquid and in part clotted, and "the inner sur- face of the wall of the sac is lined with layers of gray- ish, opaque fibrin of irregular thickness and extent. These layers may be comparatively thin, or they may fill the greater part of the cavity. They are produced by gradual deposit of the fibrin on the wall, so that those layers that are nearest the wall are the oldest, and also the shortest, because the sac has usually increased m size since they were deposited. They occasionally undergo degeneration and break down into a granular detritus, forming small cavities filled with a pulpy mass. Ordinarily the connection be- tween the wall of the sac and the adjoining layers of fibrin is one merely by contact, and there is no growth of tissue from the former into the latter. This condition seems to be true at least of all grow- ing aneurysms, but in those that have undergone spon- taneous cure, or have been cured by treatment, the development of new tissue is observed. This firm, laminated fibrin is called the "active clot"; the soft, dark clot, or "passive clot," which is fre- quently found loose in the cavity of the sac, is prob- ably a postmortem formation in most cases. The growth of an aneurysm may be stayed, and a practical cure obtained, by the deposit of sufficient laminated fibrin either to fill its cavity or thoroughly to protect its wall from the distending effect of the blood pressure, and this is thought to be the mode 398 of cure by most methods of treatment. It seems extremely improbable that this laminated fibrin is a later stage of a "passive" clot; there is every reason to believe that it is gradually deposited as such by the blood in consequence of changes or peculiar con- ditions in the lining membrane of the sac, or in the rapidity of the circulation. Under ordinary condi- tions this deposition does not take place rapidly enough to effect a cure; it occurs at some parts of the sac and not at others; its union with the sac is slight, and the blood can readily insinuate itself between the two at the edge of the layers, and as the sac en- larges fresh portions are created and left uncovered to undergo subsequent distention. If the conditions are modified by operative or other treatment that diminishes the volume and force of the stream of blood, time may be given to the tissues of the sac at the edge of the clot to become more intimately adher- ent to the latter, and thus to make the clot a per- manent protection against further increase. This is effected by granulations from the lining membrane, « Inch spread into the clot and over its surface, making it, as it were, a part of the wall of the sac, binding down its edges, and covering it with a smooth epithelial layer. The union between the walls and the layers of fibrin appears to be very slight, and limited to those layers immediately adjoining the wall, and there is no evidence that new vessels extend from the wall or between the layers of the fibrinous clot. Some aneu- rysms, after a long period of rest ami apparent cure, have begun again to pulsate and to enlarge, and this fact can be explained only on the theory of a simple mechanical obstruction that has persisted during the period of quiescence, and has then yielded and allowed the reentrance of blood, the insinuation of blood between the layers of fibrin and the wall. A cure may also follow the sudden formation of a soft "passive" clot. This fact has been demonstrated by examinations made after the rapid cure of aneurysms by the use of the elastic bandage. The first case is reported by Mr. Wagstaffe in the Transactions of the London Patho- logical Society, vol. xxix., p. 72; it was a case of popliteal aneurysm cured a few months before the pa- At the autopsy the sac was found to measure two inches in length and one inch in diameter, and to contain a central blood clot measuring one by one-half inch, and surrounded by fibrous tissue which was continuous with the sac and artery. This tissue was abundantly supplied with blood-vessels, and the artery was permanently closed above and below. The process is probably as follows: In consequence of the arrest of the current of bl I, whether by a distal plug, or by ligature, or by com- pression, the blood within the sac clots, and it proba- bly does so more promptly than within normal vessels because of the character of the inner surface of the wall of the sac. This clot fills the sac, and probably extends for a variable distance into the artery above and below the opening. This extension prevents the reentrance of blood into the sac even if the obstruction that led to the formation of the clot is afterward removed, and the latter then undergoes those changes with which we are familiar in clots formed outside the body. It divides into two portions, a central, shrunken, firm clot, composed of corpuscles and fibrin, and an ex- ternal layer of serum. The latter is absorbed b}' the neighboring tissues, and the sac correspondingly re- tracts, and its wall thickens by this retraction and Fig. 236.— Sec- tion of an Aneu- rysmal Sac Con- taining a Clot Sur- rounded by Organ- ized Fibrous Tis- sue. (Wagstaffe.) tie nt's death. REFERENCE HANDBOOK 0] THE MEDICAL SCIENCES Ani'iii} sm, External possibly by a hyperplasia of its cellular element provoked by the irritation excited by the clot, irritation involves also the adjoining wall of the artery, as is proved by the changes that occur even in normal vessels into which clots have extended. The intima thickens and sends oul cellular prolo . which perforate I hi' clot ami spread over M - surface; these new cells soon constitute a completely ned and resistant plug structurally continuoi with the wall of the artery, and provided with a 00th epithelial surface. The artery is now a- ipletel) and permanently closed on each side of aneurysm as if ligatures had been placed upon it there, and the clot is left free to undergo its natural retrogressive changes, and the aneurysm is relieved distending pressure of the arterial stream. Complete absorption of the serum reduces the clot to less than half its original size, and this reduction lowly carried further by molecular disintegration rption of the corpuscles and fibrin. This conception of the process is supported by our knowledge of the changes which occnr in blood that has clot t i'd within the body under ot her circumstances, by certain clinical features observed in aneurysms that are undergoing or have undergone cure, and by the examination of specimens. Thus, in a case of popliteal aneurysm cured by the application of the rubber bandage, a non-pulsating area of fluctuation appeared in the sac a day or two after the operation, and slowly disappeared as the tumor diminished; there can be but little doubt that it was due to the pressure of serum exuded from the clot more rapidly than it was absorbed by the surrounding tissues. Again, in .Mr. Wagstaffe's case above referred to, there was found a central blood clot of comparatively small size, closely surrounded by the thickened sac, and the artery was permanently occluded by fibrous tissue continuous with its wall and with that of the sac; and in Reid's case (Lancet, August 5, 1876), the first one cured by the use of the elastic bandage, a similar condition of the parts was found: a central blood clot, dark in color and of cheesy consistency; a con- tracted but thin sac with a few partly adherent layers of laminated fibrin; and the artery occluded by fibrous tissue for a distance of two and one-half inches above the sac. The transformation of an obliterated aneurysm into a blood cyst after many years has been observed in one case, which is apparently unique. It is reported by Reinhold ("Ihaug. Dissert.," Marburg, 1SS2; abstract in Ci ntralblatt fur Chirurgie, 1SS2, p. 571). It was a traumatic varicose aneurysm of the popliteal artery and vein successfully treated by ligature of the fem- oral artery and by compression of the sac. Nine years afterward a large, tense cyst formed, containing crystals of cholesterin and hematin, and suppurated after multiple punctures; it was then laid open, and several old blood clots and a few calcified fragments were turned out. Causes. — Anything which reduces the power of resistance possessed by the arterial wall below what is sufficient effectively to oppose, the distending force of the blood may be an immediate or a predisposing cause of aneurysm. A sudden increase of intravascu- lar pressure may combine with preexisting weakness of the wall to produce an aneurysm, but in the great majority of cases the change which leads to this pro- duction lies in the wall alone. Mr. Holmes quotes two cases in which the formation of an abdominal aneurysm appeared to have been the direct consequence of the emotion experienced by a criminal on receiving a severe sentence. Weakness of the wall may be lim- ited to a single large or small area, or may exist at many points, with the production of a corresponding number of aneurysms. This latter condition is termed the aneurysmal diathesis, and although the affection is usually single, as many as sixty-three aneurysms have been found in one individual. The weakness of the wall i i ! ill of change in i he innei and i ii cially the middle, coats of thi I this change maj be either the hyaline degeneration above described, or the one known an atheroma. Among the predisposing causes, therefore, mu I bi con all those w hich lead to degi aeral ion of th wall. The statistics collected i>.\ Mr. Crisp show that of 551 spontaneous aneu : all kinds, only two were of the pulmonary artery. 1 7."i of tic tho aorta, fifty-nine of the abdominal aorta, 137 of the popliteal artery, sixty-six of the femoral, twenty- four of the carotid, twenty-three of the subclavian, t wenty of t he innominate, ami eighteen of t he axillary. The disease is mosl common between the ages of thirty and fifty year-, and i- verj rare in childhood; have I n operated upon at eight and nine years. Broca claimed that the liability to aneurysm increased with advancing years in the arteries above i he diaphragm, and diminished in those below it. Aneurysms of the arteries of the extremities are much less frequent in women than in men. but there ap- pears to be no such difference as regards internal aneurysms. This unequal distribution as regards the artery, the age, and the sex, indicates some of the . both general and special. Among the gen- eral causes are habits of life and peculiarities of con- stitution -which increase the arterial tension or diminish the strength of the arterial walls; the special ones are anatomical peculiarities and local lesions, changes, and injuries. The habits of life which act as predisposing causes are excess in the use of alcoholic drinks, and occupa- tions which call for the exertion of much muscular effort. The influence of syphilis has been alleged. Modern methods of diagnosis of syphilis ought to give us more accurate data; in the same way the more vigorous action of salvarsan may give better results than the older usually inefficacious mercurial treat- ment. The gouty or rheumatic diathesis predis- poses to it. The influence of muscular effort, so far at least as regards external aneurysms, is shown by the greater prevalence among males than among females, and the greater frequency during the prime of life, notwithstanding the fact that degenerations of the arterial walls are more common in advanced life. Follin quotes in support of the influence of alcohol a remarkable statement made to him by the Dublin surgeon, Colics, to the effect that while the Father Mathew Temperance Societies flourished in Ireland, aneurysms were much less frequently seen than before or since that time. The anatomical peculiarities which influence the occurrence of an aneurysm are changes in the direction of an artery (as the arch of the aorta), normal enlarge- ments of its caliber (as at the upper end of the car- otid), bifurcations, and the neighborhood of joints which are habitually and violently extended and flexed (as the knee and hip). The local changes which are to be regarded as exciting causes are the changes already described as occurring in the arterial wall and other changes or injuries which diminish its power of resistance or break its continuity. Thus the sharp edge of a calcified atheromatous patch may cut through the intima and admit the blood into the rent, with the subsequent formation of a real aneurysm, or of the variety known as dissecting aneurysm. Or the middle coat may be ruptured by being over- stretched, and the part thus weakened will be ex- panded to form an aneurysm; or ulcerative in- flammation outside the vessel may weaken, or even perforate its wall, leading, in the former case, to the formation of a typical aneurysm, and in the latter, to the transformation of an abscess into an aneurysm. Or, rarely, the process set up by a ligature upon an artery may extend beyond what is needed for the sealing of the vessel, and so weaken the adjoining portion by modifying its middle coat that it yields under the pressure of the blood and expands into an 399 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES aneurysm. Or an embolus may lodge in an artery and lead to the same result by the same process; this seems to be especially probable when the embolus has formed during ulcerative endocarditis, and the explanation is to be found in the septic or virulent qualities then possessed by the embolus. Four cases of this kind were reported by Dr. James F. Goodhart, in the Transactions of the London Patho- logical Society, 1S77, vol. xxviii., p. 98: in three of them the aneurysm occupied the middle cerebral artery, or one of its branches; in the others, the posterior cerebral artery. Symptoms and Progress. — When an aneurysm forms suddenly by rupture or perforation of an artery, or in consequence of a violent effort or emotion, its formation is accompanied by sharp pain and the more or less prompt appearance of a tumor, if it is so situated that a tumor is recognizable. But ordi- uarily the formation is slow, and the patient's attenl ion is first attracted by the presence of a tumor. This is situated in the line of an artery, is not adherent to the skin, is slightly movable, smooth and regular in outline, usually globular or ovoid, soft and compressi- ble, and pulsates synchronously with the heart. If steady pressure is made upon it, its size may be more or less diminished while the pressure is made, but it immediately regains its former volume when the pressure is removed. If it is grasped between the thumb and fingers or between the two hands, the pulsation is found to be expansile, that is. the fingers or hands are pushed apart by it, not simply lifted by it. If the ear is placed upon it a sound is heard corresponding to the pulsation; this is the aneurysmal bruit; and while it may vary somewhat in character in different cases, it is usually harsh rather than soft or blowing; it may be limited to the time occupied by the pulsation, or may extend over the entire interval from the beginning of one pulsation to that of the next. If pressure is made upon the artery above the tumor, the latter diminishes somewhat in size, and the pulsation and bruit cease. The pulsation in the distal branches of the artery may be normal or diminished; and if the tumor presses upon the corre- sponding vein, the limb may be edematous and swollen. The compressibility and softness of the tumor are modified by the amount of laminated fibrin within the sac. Pain may accompany aneurysm when once formed and is due either to stretching of nerves or to pressure upon, and inflammatory processes excited in them and other adjoining tissues. The tendency of an aneurysm is to increase in size; for the absence from the wall of the sac of a muscular coat the most efficient agent to withstand the expand- ing blood pressure, leaves the wall unprovided with any tissue able successfully to oppose this pressure. The growth may be rapid or slow, according to cir- cumstances, chief among which are the size of the opening by which the sac communicates with the artery, the firmness of the surrounding tissues, and the readiness with which the blood in the aneurysm clots or deposits laminated fibrin upon its wall. The enlargement may be uniform, or more marked at some points, and may take place more rapidly at certain times than at others. The natural tendency of an aneurysm is to spread and finally to rupture, either by gradual weakening of its wall or by ulceration into a natural adjoining cavity or through the skin. As it approaches the surface the skin becomes tense, adherent, and inflamed, and may ulcerate or become gangrenous. The subcutaneous tissues may be similarly affected, and thus an abscess may form between the sac and the skin, into which the aneurysm may rupture either before or after the abscess has opened exter- nally. The inflammatory process outside the sac has been thought to favor coagulation of the blood within it, and thus to lead to a temporary or even a perma- nent arrest of the disease; but ordinarily free hemor- rhage follows the rupture and requires extreme measures for its arrest, if indeed arrest is possible. The most favorable, and one of the possible termi- nations of aneurysm, is its spontaneous cure by coagu- lation of the blood within it. Some of the conditions which provoke or favor this occurrence have already been referred to. They may all be classified under three heads: (1) Those which favor clotting in the sac by retardation or arrest of the current through it; (2) those which increase the coagulability of (lie blood; (3) those which provoke coagulation through change in or about the wall of the sac. (1) Retardation or arrest of the current; and (2) Conditions which increase the coagulability of the blood. It has been abundantly proved, both clinically and by the study of specimens, that total arrest of the current in the sac is not necessary for the coagulation of the blood contained in it, but that a partial arrest or slowing, effected by influences acting upon the general circulation or only upon the blood occupying portions of the sac, may either begin the process or promote the extension of the process after it has been begun. Most aneurysms of any size contain lami- nated fibrin adherent to some portion of the wall, and some are found completely filled with it, or so nearly filled as to leave only a small canal through which the current is maintained. When these clots are small, they habitually occupy those portions of the sac in which the circulation was apparently the least rapid, and it has been observed that the adoption of measures or the occurrence of changes which have diminished the rate of flow, or the quantity of blood passed through the vessel upon which the aneurysm is situated, has been followed by a gradual cure through the deposition of fibrin. The permanency of such a cure depends upon the maintenance of the reduction in the rate or volume of the blood current, or upon the creation of such relations between the clot and the wall of the sac that the former becomes a permanent part of the latter and protects all por- tions of it from the action of the expanding force of the blood. These relations consist in the formation of a membrane by proliferation of the cellular ele- ments of the intima of the artery, and the spread of this membrane over the edges and perhaps over the whole of the exposed surface of the clot, in such a way as to prevent the insinuation of the blood between the clot and the wall, and to give a smooth epithelial surface over which the blood passes without depos- iting additional fibrin. The causes of retardation or arrest are various. They may be found in the shape of the sac, in the general condition or habits of the patient, or in special modifications of the flow through the artery itself. Pouched sacs, or sacs with small necks, are more favorable to the occurrence of clotting than are fusiform dilatations or sacs with large, free openings, because the blood that enters does not immediately leave them, but forms a sort of eddy beside the general stream in which the current is slow or almost nil. Of the causes arising in the general condition or habits of the patient, the first and most important is continuous rest in bed for Weeks or months, combined with a light, non-stimulating diet. Other causes, which may also act by increasing the coagulability of the blood, are bleeding, either large or small and repeated, and the internal use of various drugs, such as digitalis, tartar emetic, veratrum viride, iodide of potassium, acetate of lead, ergot, and the chloride of barium. Cures have followed the use of each of these measures, alone or in combination, but it is not always easy to determine how much credit is to be awarded to "the treatment in any one case. Retardation or arrest of the flow may also be caused by obstruction of the orifice of the sac, if it is small, or of the artery above or below the aneurysm. The most common agency in producing this change is the 400 REFERENCE HANDBOOK OF THF MEDICAL SCIENCES Aneurysm, External detachment of a fragment of fibrin from the wall of the sac and its lodgment in the neck of the s:ir, or in the artery below. The latter occurence is habitu- ally accompanied by severe pain in the limb, and is evidenced by arresl of pulsation in the distal branches ( if the artery. A euro by this mechanism has been observed a number of limes, and it forms the basis of a method of treatment suggested by Sir William Ferguson, in which the forcible detacl nt of a clot from the wall is sought to be effected. If the de- tached 'lot is small, it may lodge on the spur of a bifurcation, and then grow in size by additional de- posits of fibrin until it obstructs one or both of the branches, and in such a case retardation precedes complete aires!. This possibility of the detachment of small clots and their passage into the distal branches of the artery involves the risk of other changes far different from the cure of the aneurysm. The arrest, of the circulation may lead to gangrene of the lower portion of the limb, total or partial, according to the seat of the obliteration; and if the aneurysm is situated upon the arch of the aorta or upon one of the vessels going to the head, the emboli may lodge in the vessels of the brain and cause death promptly. When there is merely retardation of the current the cine takes place by the gradual deposit of lamina led fibrin: and when there is total arrest, it takes place probably by coagulation in mass of all the blood within the sac, and the subsequent shrinking of the clot and sealing of the vessel by the production of fibrous tissue, as has been described above. Another alleged cause of retardation of the stream is pressure of the tumor upon the proximal portion of th ' artery, but no cases have been reported in which this mechanism has been demonstrated. Its supposed possibility rests upon theoretical grounds alone, and while it may be admitted as a possibility, there is but little reason to believe it has ever taken place. (3) Conditions which provoke coagulation through change in or about the wall of the sac. Inflammation of the sac, or of the tissues immediately overlying it, is alleged by Broca and others to be a cause of coagulation within it and of consequent cure. Mr. Holmes thinks this assertion has never been demon- strated, and attributes the cure, in the eases that have been cited in support of the theory, to impaction of a clot. There is no doubt that inflammation about an artery or vein can and does often lead to the formation of a thrombus within the vessel, but the conditions in an aneurysmal sac are so different that it is perhaps unjustifiable to argue from a sup- posed analogy. The sudden formation of a soft elot within an aneurysm may excite inflammation and suppuration of the sac with subsequent rupture. In a few cases this process has been followed by a cure; but the cure must be attributed to the obstruction of the vessel, either by the original clot previous to the rupture, or by a secondary clot after the hemorrhage that has followed the rupture. In like manner, tardy suppuration may follow cure, and after an aneurysm has remained quiescent and shrunken, in fact cured, for months or even years, such suppuration may lead to the casting out the clot in whole or in part. Changes in laminated fibrin after the cure of an aneurysm are slight and gradual, and rarely amount to more than a diminution in size by shrinking; some- times the fibrin becomes soft, and sometimes lime salts are deposited in it. A unique case of later trans- formation into a blood cyst has been mentioned above. Diagnosis. — The typical symptoms of aneurysm are the existence of a more or less well-defined tumor that pulsates synchronously with the beat of the heart, has a distinct intermittent bruit, and diminishes in size while pressure is made upon it or upon the proxi- Vol. I.— 26 mal portion of the artery from which it arises. Hut these signs may lie variously modified or abolished by the varying conditions that have been described above, or may be undemonstrable because of the position of the tumor, or may be simulated by those of other affections. An additional sign is Minn-limes found in a difference In the character of the pulse in the distal branches of the artery when compared with thai in the branches of the corresponding artery of the outer side, a difference that may be recognized by the linger, but much more certainly by the sphygmograph. The symptoms in external aneurysm may be modified by the partial or complete consolidation of its contents, or by the temporary obstruction of its orifice, either of which occurrences may greatly diminish Or arrest, the pulsation and bruit. The affections with which an aneurysm is most likely to be Confounded are solid or liquid tumors overlying an artery and very vascular tumors lying in or near the course of a large artery. In all, the common signs an' a pulsating tumor with bruit, and the circumstance that the pulsation and bruit may be arrested by pressure on the artery. The pulsation of an aneurysm is expansive, the tumor enlarging later- ally at each pulsation; that of an overlying tumor is a simple lifting of the entire mass; but this difference cannot always be recognized with certainty, or if the fingers cannot be pressed down to the widest part of I he tumor, the simple rising of the sloping sides of the globular mass between them forces them apart and simulates lateral expansion. A bruit may be caused in an artery or vein by pressure upon it. In a vein such a bruit is harsh and continuous; in an artery it is intermittent and more "blowing" in character than that of an aneurysm. In the case of a suspected liquid collection simulat- ing aneurysm, the diagnosis may be aided by aspira- tion with a fine needle. An aneurysm has been mistaken for an abscess frequently enough to make great caution necessary in the diagnosis and treat- ment of any supposed abscess lying in the course of a large artery. The fingers should always be pressed deeply into the swelling in search of pulsation, and even if an abscess is certainly present, it should be remembered that it may have formed over an aneurysm. As pulsation and bruit have their origin in the stream of blood brought by the artery, pressure upon the proximal portion of the vessel will arrest them, whether they belong to an aneurysm or are simply communicated through a tumor. Vascular tumors, especially those arising from bone, often have well- marked pulsation and bruit: but their pulsation is less "heaving" or massive" than in aneurysm, and the bruit is rarely well marked. The diagnosis may be extremely difficult, or only possible by the aid of exceptional explorations. In a case of large pulsating tumor of the gluteal region, under the care of Prof. Henry B. Sands, in the Roosevelt Hospital, New York, in 1880, the diagnosis of aneurysm was made by passing the hand into the rectum, and thus learning that the internal iliac artery was enlarged, the enlargement increasing from above downward to the sacrosciatic notch. The frequent presence, in vascular tumors, of large collections of blood contained within sacs formed by the rupture or dilatation of capillaries or small vessels, increases the resemblance to an aneurysm. An aneurysm which has just ruptured into the adjoining tissues does not pulsate, and may have no bruit; under such circumstances the diagnosis must be made by the history of the case, the preexistence of a pulsating tumor, and the cessation of the pulsa- tion coincidently with a marked change in the shape and size of the tumor. In like manner, where an artery has just been ruptured or perforated and the blood has been effused into the adjoining tissues, 401 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES pulsation and bruit are not present until after the effusion has become circumscribed by a distinct firm wall composed of the condensed tissues ("trau- matic aneurysm" or "ruptured artery"). For the differential diagnosis of arteriovenous aneu- rysm and cirsoid aneurysm or arterial varix, vide infra. Prognosis. — The gravity of the prognosis varies with the artery involved, and the size and character of the aneurysm. In internal aneurysms the prognosis is very grave; in external aneurysms it is commonly much less so, since in most of them suitable treatment offers a reasonable hope of cure. Treatment. Medical treatment. — The medical treat- ment of aneurysm, especially of internal aneurysms, consists in absolute rest in the recumbent position, maintained for weeks or months, combined with a restricted diet, and aided, perhaps, by the use of vari- ous drugs. The absolute rest and the low diet are un- questionably the most efficient part of the treatment, and the drugs, even those for which most has been claimed, are only adjuvants of uncertain and often very doubtful utility. Systematic treatment of this kind dates from the time of Valsalva, and even in his hands the rest was subordinate to repeated venesec- tion, which he carried to such an extent that rest in bed was a matter not of choice, but of necessity. This active depletion was never regarded with much favor, and as it was long deemed an essential part of treatment by rest, the latter shared in the disfavor of its associate, and patients affected with internal aneurysms were habitually looked upon as beyond the reach of art, and the interference of the physician was restricted to relief of pain and the occasional employment of drugs from which it was thought some benefit might possibly accrue. To Mr. Tufnell of Dublin belongs the credit of demonstrating the value of absolute rest in bed and restricted diet in pro- moting a cure or affording great relief. He insisted upon the absolute maintenance of the recumbent posture, and restricted the amount of food to about eight ounces of solid food and six ounces of liquid daily, the solid food being bread, butter, and meat, the liquid, milk and a little claret wine. Of drugs, the iodide of potassium has been most employed, in doses of from half an ounce to one ounce daily. A number of cases of aortic aneurysm appar- ently cured or greatly relieved by its use have been reported. Salvarsan might be useful in certain cases. Digitalis, veratrum viride, and ergot have also been used, with the object of slowing the circulation; occasional supposed cures or temporary arrests by their agency have been reported, but they are not regarded with favor by the authors of systematic treatises on the subject. Ergot is given internally in the form of the fluid extract, or subcutaneously as ergotine. Mr. Holmes regards the acetate of lead as offering the best promise. Dr. F. Flint reported a case of aneurysm of the abdominal aorta apparently cured by the use of the chloride of barium in doses of from one-fifth to three-fifths of a grain three times daily for about five months, after Tufnell 's method had entirely failed. The most rapid improvement coincided with the smallest dose. Surgical methods of treatment may be grouped in three classes: 1. Radical obliteration of the sac by opening it and tying the artery immediately above and below its point of communication with the aneurysm. This is known as the "old method," or the "method of Antyllus." Under the same head may be included the method of extirpation of the sac. with ligature of the artery above and below; and the Matas operations: (a) Obliterative endoaneurysmorrhaphy; (6) Recon- structive endoaneurysmorrhaphy. (See under Ar- teries, Surgery of the.) Suture of each opening in arteriovenous aneurysm or excision of the injured vessel with end-to-end Union of the two segments, or implantation between them of a segment of another vessel (vein). See Binnie, Operative Surgery, fifth edition. 2. Permanent or temporary arrest of the afferent stream at a point on the proximal side somewhat removed from the aneurysm, (a) Ligature of the artery (Anel's method, or the Hunterian method). tin Compression of the artery — direct, indirect, digi- tal, or tentative by apparatus whose pressure can be regulated or by apparatus which can be re- moved, (c) Esmarch's elastic bandage, (d) Flexion of the limb. 3. Permanent arrest or obstruction of the stream on the distal side, (a) Distal ligature. (6) Manipula- tion to produce an embolus or impacted clot. 4. Rapid coagulation of the blood in the sac (with or without temporary arrest of the stream), (a) Co- agulating injections. (6) Introduction of solid bodies, (c) Galvanopuncture and the introduction of a wire plus galvanism. 5. Promotion of the formation of a laminated clot by irritation of the wall — "needling." 1. The "old method" (or the method of Antyllus). The aneurysms with which the ancient surgeons had mainly to deal, or at least those to which operative in- terference was mainly limited, were traumatic an- eurysms at the bend of the elbow following venesec- tion. It has been claimed for them that they knew and practised the method of cure by ligature of the artery in continuity above the sac, but Hodgson's statement, which is quoted by Holmes in support of this claim, does not fully and accurately present the practice. Ligature of the brachial artery "three or four finger-breadths below the axilla" was indeed recommended by Aetius in the fifth century, but only as a preliminary to the opening of the sac at the elbow and the application of another ligature there, and solely with the object of preventing hemorrhage during the operation proper. The main "object of treatment was to remove the clot, which was thought to be a source of danger, and to prevent subsequent hemorrhage by obliterating the artery or closing the opening by which it communicated with the sac. The operation appears to have fallen into disuse and not to have been revived until about the seventeenth century, when it was again used with various modifica- tions, but at first only in traumatic aneurysms at the elbow. It appears to have been first used in popliteal aneurysm by Keyslere; the date of his first operation is not known; his second and third were done in 1747 and 174S respectively. His first three cases were successful; the fourth ended fatally. The method of operation as practised in popliteal and brachial aneurysms until the end of the eight- eenth century, was to control the artery by a tourni- quet or the fingers, divide the sac by a longitudinal incision, turn out the clots, find the point of communi- cation with the artery, isolate the latter, and tic it above and below the opening. The cavity was then packed with lint and allowed to fill by granulation. The difficulties and the dangers were great. The frequency of secondarj' hemorrhage was thought by Hunter to be due to the diseased condition of the arterial wall near the sac, where the ligature was applied, and this has always been deemed one of the most weighty reasons for preferring the Hunterian method, in which the ligature is placed upon a more distant and presumably healthy part of the artery. It must be remembered, however, that secondary hemorrhage was much more common in former days, after all operations in which a large artery was tied, than it is at present, when it has become very rare after ligature with catgut or aseptic silk; and that arteries so degenerated, or even calcified, that they broke when the ligature was drawn tightly, 1 remained securely closed by slighter pressure, and the wounds have healed without accident. .Mere- over, recent experience with the catgut ligature in the "old" operation and in extirpation of the sac has 402 REFERENCE EANDBOOK OF THE MEDICAL SCIENCES \neiirysm. External shown that the chance of s ndary hemorrhage is !-. The objection raised against the old method, the condition of the adjoining arterial wall is altered, cannot properly be urged in the case of a traumatic aneurysm; and the only other possible objections are, that the operation is more difficult and the wound larger. Syme's method of operating when the artery could oot be controlled on the proximal side of the sac was to make an incision into the tumor just large enough to admit his finger, with which he then felt for and compressed the opening in the vessel. If he could not thus find the opening, he enlarged the incision and then introduced a second and third finger, and. in , , 1M — so says Holmes — the entire hand. When the opening was found and commanded, he si ill further enlarged the incison, turned out the clots, and denuded and tied the artery above and below. Extirpation of the sac is now done as for the re- moval of a tumor. The mass is exposed by a long incision, the artery is tied above and then below, and the >ae is dissected out with great can- to a\ oid injury to the vein. The water operation is described in the article on ' ry of the. 2. Permanent or temporary arrest of the afferent stream at a point on the proximal side somewhat re- moved from the sac. Ligature by Anel's method, or the Hunterian The question of priority in the introduction of the method of ty-ing the artery above the sac, as Fig. 237. — Different Forms nf Ligatures for Aneurysm, a, Ariel's; b, Hunter's; c, Brasdor's; d, Warurop's; e, Antyllus's. now practised, has given rise to much controversy, but must here be dealt with very briefly. It is claimed by the French for Anel, a French surgeon itising in Rome in 1710, and by the English for John Hunter in 17S5. The reader who is curious in the matter is referred to Broca (" Des aneVrysmes, " Paris, 1856), to Holmes ("A System of Surgery "1, and to a paper by the writer in the New York Medical Journal, November 1, 1SS4. The facts, in brief, are as follows: January 30, 1710, Anel treated a traumatic aneurysm at the bend of the elbow by tying the artery close above the sac without opening the latter, and thereby effected a cure. The patient was a priest. The case gave rise to much discussion, the account of it was reprinted in several books and journals, and the method was subsequently used, before 1785, in at least three other eases, in one of which the ligature was applied about two inches above the sac (Broca. p. 446). June 22, 1785, Desault (after having a few months previously sought to cure an axillary aneu- rysm by compression of the subclavian) treated a popliteal aneurysm by tying the artery. " immediately below the ring of the third adductor," that is, at th ■ point where the femoral artery ends and the popliteal artery begins; the aneurysm was cured, and the patient died eleven months later of disease of thelower end of the tibia. December 12, 1785, John Hunter treated a popliteal aneurysm by tying the femoral artery and vein "rather below- the middle of the thigh."* In tl ing March, 1786, Di Inning knowledge of Huntei operated upon another anil tied the artery at a -till higher point, dividing the sartori i e it. Bunter repeated the operation four times within four years following hi ie vein as . i lie artery, except in the last I wo; I >ei aull shortly after his owe second case. These facts are riot disputed; the controversy lias arisen over the principles which are thought to I led, in the minds of the different opi \ne|, Desault, and Hunter), to the adoption of the method. It is claimed by the English (Guthrie, Holmes) that Anel did not know what he was doing, did not appreciate the importance of the method, the m by which it affected a cure, and it- applicability to I aneurysms than those at the elbow, and that, as he used it. it was radically defective in placing the ligature too close to the sac, and without the interven- tion between I he tun of any collateral branch given off from the artery; that, in short, it wa a mere happy e, stumbled upon without reflection, and passed without appreciation; that Desault's, in like manner, was a mere experiment, but that Hunter's was the result of profound reflection and reasoning upon the nature of the disease and the manner in which coagu- lation of the blood in the sac is effected, and especially of his knowledge of the fact thai complete shutting off of the current from the sac was not necessary. The original reports, on examination, do not appear to justify any of these claims, which seem to have no more solid basis than ignorance of what Anel and Desault really thought, and the crediting of Hunter, before his operation, with knowledge which he ob- tained at a later period. Hunter's identification with the operation was in large part the result of his exceptional authority at the time, the publicity which attended or was given to the act, the frequent repetitions, and the generalization which promptly followed it, and also of the great ability with which he set forth the principles upon which it rested. These in themselves are an ample title to recognition and re- spect, and Hunter's glory may well be left to rest on them without robbing others of their just due. Three months after Desault's first operation, and three months before Hunter's first operation, at a consultation held in London on a ease of femoral aneurysm as large as an orange, in which Hunter took part, all agreed that it was impossible to resort to the operation ordinarily practised upon aneurysms, and recommended pressure on the artery in the groin; the attempt was made, and abandoned because of the pain it caused. It is apparent that at this time Hunter had not developed his method. The argu- ments that led Hunter to tie the femoral artery for popliteal aneurysm, according to Home, his pupil, assistant, and reporter (loc. cit., p. 145), were "that the disease often extends along the artery for some way from the sac; and that the cause of failure in the common operation arises from tying a diseased artery, which is incapable of union in the time neces- sary for the separating of the ligature." If the artery should afterward give way [if tied just above the sac] there will not be a sufficient length of vessel remaining to allow of its being again secured in the ham. To follow the artery up through the insertion of the triceps muscle, to get at a portion of it where it is sound, becomes a very disagreeable part of the operation; and to make an incision upon the fore part of the thigh, to get at and secure the femoral artery, would be breaking new ground, a thing to be avoided, if possible, in all operations. Mr. Hunter, from having made these observations, was led to * Everard Home, in Transactions of a Society for the Improve- ment of Medical and Surgical Knowledge, London, 1793, p. 148. This appears to be the first official publication of the case; the paper is not dated, but it is printed between two which are dated Sep- tember, 17S9, and September, 1790, respectively. 403 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES propose that in this operation the artery should be taken up in the anterior part of the thigh, at some distance from the diseased part, so as to diminish the risk of hemorrhage and admit of the artery being more readily secured, should any such accident happen. The force of the circulation being thus taken off from the aneurysmal sac, the progress of the disease would be stopped; and he thought it probable that, if the parts were left to themselves, the sac with its contents might be absorbed and the whole of the tumor removed; which would render any opening into the sac unnecessary." It is plain, from this, that Hunter's idea in seeking the artery at a higher point was simply to avoid secondary hemorrhage and to make its treatment. if it should occur, easier; and the extent to which this idea preoccupied his mind is shown in the strange additional precautions he took in the matter of the ligature itself. He tied the artery with four ligature-;, " but so slightly as only to compress the sides together. The reason for having four ligatures was to compress such a length of artery as might make up for the want of tightness, it being wished to avoid great pressure on the vessel at any one part." According to Holmes, "the great merit of Hunter consists in his having seen, first, that it was not necessary to turn the clots out of the aneurysmal tumor; and, second, that it was not neces- sary to stop the circulation through it absolutely, but only, as he said, 'to take off the force of the circula- tion.' " The first of these was certainly appreciated by Anel and Desault, for they saw their patients get well; the second is difficult to explain if it is based upon the fact that the ligatures were tied loosely, for they certainly were intended to, and did, cut out, and therefore occluded the artery entirely; and in Hunter's subsequent operations he used a single ligature and tied it tightly, so that if this was his opinion and object at first, he subsequently aban- doned it. The idea, moreover, is expressed by Home (loc. cit., p. 150) as a conclusion drawn from what was found at the autopsy eleven months later: "The conclusion to be drawn from the above account appears a very important one, viz., That simply taking off the force of the circulation from the aneu- rysmal artery is sufficient to effect a cure of the dis- ease, or at least to put a stop to its progress." It seems much more reasonable to infer that Hunter's object in tying the ligatures loosely was to give the artery more time to become sealed before the ligature cut through. (See the first quotation from Home given above.) The statement has been generally quoted as mean- ing that Hunter proposed to leave one or more col- lateral branches between the ligature and the sac, but there is nothing in the account of the operation or of the autopsy to justify such an opinion. "The femoral artery was impervious from its giving off the arteria profunda as low as the part included in the ligature, and at that part there was an ossifica- tion for about an inch and a half along the course of the artery Below this part the femoral artery was pervious down to the aneurysmal sac, and contained blood, but did not communicate with the sac itself, having become impervious just at the en- trance [italics ours]. ...... The popliteal artery, a little way below the aneurysmal sac, was joined by a small branch, very much contracted, which must have arisen from the profunda, or the trunk of the femoral artery." This is the only collateral branch mentioned, and one cannot see how the conclu- sion is to be avoided that even if the phrase "to take off the force of the circulation" meant any more than "to arrest" or "cut off" the circulation, it meant only that the artery was left containing blood, and that this blood was in communication with that brought to the lower part of the same artery by col- laterals coming from above the ligature. It would be interesting, too, to know by what "profound reason- ing Hunter excogitated the principle" (Holmes) of including the vein in the ligature with the artery. Even if Hunter afterward declared the presence of a collateral branch between the ligature and the sac to be a favorable condition, it does not affect the original conception; and furthermore, the existence of such a collateral branch is not essential to the method, and it is not found when the carotid or femoral is tied, or in some cases when the external iliac or subclavian is. In short the method as now employed is to place the ligature at the nearest con- venient point, sufficiently far above the sac to find the artery probably healthy; and the claim that has been made that complete arrest of the circulation is more dangerous than partial arrest, because it leads to the formation of a passive clot which is likely to provoke suppuration of the sac, has been proved, especially by the experience with the Esmarch bandage, to be incorrect, or at least the danger of exciting suppuration is much less than was claimed. The changes within the sac by which a cure is effected after ligature are similar to those above described as effecting a spontaneous cure. The closure of the artery relieves the sac from all expanding pressure, except the slight amount which may be exerted by the blood that comes into the artery below the sac or between it and the ligature through collateral branches. The pressure being removed, the sac shrinks, the blood within it either coagulates in mass, forming a dark passive clot, or a slight movement persists in it and laminated fibrin is deposited on the wall. Pulsa- tion in the sac ceases as soon as the ligature is tied, and usually remains permanently absent, but in si ime cases it returns after a longer or shorter interval and lasts for a few hours or days. This return is due to the freedom and rapidity with which the col- lateral circulation is established. The blood leaves the artery through the branches given off above the ligature, which dilate to accommodate the increased supply, makes its way through the minute terminal branches and capillaries into the terminals of the branches given off from the main artery below the ligature, passes through them in the retrograde direction, and thus regains the main artery to be distributed as before through its terminal branches. The greater the length of artery that has been obliterated by the ligature and disease, the greater the difficulty of the reestablishment of the circulation, and thus it is found that when two or three aneurysms are situated upon a single artery, or when, on account of secondary hemorrhage, a second ligature has been placed upon the artery at a higher point, the proba- bility is great that the circulation will be reestab- lished too slowly or imperfectly to preserve the life of the tissues, and the occurrence of gangrene is to be feared. The method of operation is to expose the artery by a suitable incision, denude it just sufficiently to allow an aneurysm needle to be passed under it, and to tie it with a sterile ligature. Silk may be used, but most surgeons prefer today the thoroughly reliable catgut; when moderately chromicised this remains unchanged ten days or more. The chief dangers of the operation are secondary hemorrhage and gangrene. Before the introduction of the antiseptic method these dangers were so great that the mortality, after ligature of the fem- oral, for example, was about twenty-five per cent. They are now very much less. In twenty-nine eases of ligature of the principal arteries with catgut, by New York surgeons, collected by Stimson in 1880 (.4m. Jour, of the Mid. Sciences, January, 1S81), there was no secondary hemorrhage, and only one ease of gangrene; the latter was of the foot, after ligature of the common iliac artery, and was followed by recovery. The diminution of the risk of secondary hemorrhage is plainly due to the avoidance of sup- 404 REFERENCE HANDBOOK OF THE MEDICAL SI II NCES Aneurysm, External Duration about the ligature, and the freedom from gangrene appears to be the result of the same rapidity and ease oi healing, through diminution of the inter- ference with the \Ou by the inflammatory process. The attempt has been several times made to dimin- ish i hi' chance nf I lie occurrence of gangrene by rep edly compressing the artery above the aneurysm for several days before tying it, in the hope of thereby lually enlarging the collaterals, and belter fitting them for carrying on the circulation when if is finally thrown entirely upon them. The result lias not liorne out the expectation; on the contrary, gangrene has followed the attempt in a larger proportion of cases than when the artery lias been tied without preliminary compression. A satisfactory explanation lot been found. i n her ill results of the ligature of the main artery of a limb may be permanent deterioration of its nutrition, of nerve and muscular power, persistent or recurrent ulceration of the skin, and suppuration of the sac. In order to diminish the chances of the occurrence of gangrene, the limb should be wrapped in cotton immediately after the operation, and kept thus pro- tected from losing heat until the circulation is shown to be fully reestablished. If its temperature is found main too low, external heat should be cautiously applied in the form of hot bottles, bricks, or sand, but care must be taken that the heat thus applied is not much above the normal body heat, lest it should cause blisters. Good results have been reported from the use of baking by suitable apparatus. The temperature can be raised to 300°, provided moisture is excluded. Suppuration of the sac may occur, and either cause spontaneous rupture or make an incision necessary. The opening may be followed by dangerous hemor- rhage, or the communication between the sac and the patent portion of the artery may have previously become permanently obliterated. Sometimes pres- sure is sufficient to arrest the hemorrhage and lead to a final cure by granulation: in other cases, the clots will have to be turned out and all bleeding points secured, or a second ligature may be applied between the first one and the sac. A second ligature above the first greatly exposes to gangrene. If pulsation returns permanently in the sac and the tumor again begins to grow, several courses are open to the surgeon. If the aneurysm is at the knee, groin, or elbow, flexion should first be tried, and this failing, perhaps galvanopuncture. If resort to opera- tion becomes necessary, the artery may be tied again between the first ligature and the sac, or the "old operation" of incision into the sac and ligature of all vessels entering it may be done. Both methods have proved successful. The numerous statistics that have been collected of the various results following treatment by ligature do not furnish a fair basis for estimating the chances after ligature with antiseptic catgut or with silk, and treatment of the wound by modern methods. There is, therefore, good reason to believe that the operation has become, under antiseptic methods of treatment, much less serious than it formerly was. In like manner the aseptic ligature has caused the entire abandonment of various devices (metallic ligature, artery constrictor) designed to diminish the chance of the occurrence of secondary hemorrhage, except for the methods of Halsted and Matas whereby compression is produced by metallic bands which can be removed or their pressure effects modified. iM Compression of the artery, direct, indirect, and digital. Direct compression is made upon the artery by acupressure needles or wires, threads, or forceps, after incision of the skin and exposure of the vessel; indirect compression is made by suitable instruments or weights resting on the surface over the artery; digital compression is made by the fingers. Indirect eompre sion is an older method even than ligature of the artery, and was em ployed, alt hough un- successfully, by Desault in the treatment ol an axillary aneurysm a few month before he first treated a popliteal aneurysm by ligature, as mentioned above. It is claimed for Hunter, al o, that he was the real originator of the treatment bj eompre -inn, because In- showed that complete arre I ol the circulation was unnecessary, and that the compression might be partial or intermittent, and because all previous operators sought to effect a cure by obliterating the artery .it the point pressed upon, a statement which does not appear to be bo] in m! by the report- ol their However that may be, the for r theory that a passive clot was a source of danger, and that persist- ent pressure upon the artery to arrest the circulation for several hours was, therefore, a more dangerous method than intermittent or inc plete arrest, which would give a laminated clot of slow formation, is now abandoned, and, as a rule, when compression is used, it is with t he aid of anesthesia or morphine, is forcible enough completely to arrest pulsation in the -ae. and is continued until the contents of the sac have coagulated. Intermittent, incomplete arrest is occasionally used under exceptional circumstances. In a few cases in which pressure above the sac could not be made, complete arrest of the circulation below it, usually by the elastic bandage, has effected a cure. See Distal Ligature, below.) The method of cure by this means varies in the different cases; in some it is by the deposit of laminated clot, in others by a soft passive clot. The changes in the aneurysmal sac are the same as those above described, and the dangers of the method are the same as after ligature, with the exception of secondary hemorrhage. A unique consequence, reported by Pemberton, was the formation of a communication several months afterward between the artery and vein at the point where pressure had been made, resulting in an arteriovenous aneurysm that finally caused the patient's death. The operative methods include the use of weights or of special instruments having the general character of a truss. The latter are numerous and varied, but all consist essentially of a branch to make counter- pressure without circular constriction of the limb, and of a pad which can be screwed or bound down upon the artery with suitable force. For weights, bags of -hot are used, or pieces of lead moulded to fit the parts. They may be allowed to rest entirely upon the limb, or may be suspended by an elastic cord. Prolonged complete arrest of the current requires the aid of anesthesia, for the pressure soon becomes very painful; anesthesia may be safely prolonged for many hours. It is well to aid the control of the circu- lation above by pressure also below, or by tightly bandaging the limb below the aneurysm. Digital pressure, which had previously been em- ployed in two cases as an aid to compression by instru- ments, was first used as the sole means of cure by Jonathan Knight, of New Haven, Conn. The case was one of popliteal aneurysm, and a cure was effected in about two days. The plan has since been employed in a large number of cases, and with a large measure of success. Fischer's statistics, quoted by Holmes, contain ninety cases, with seventy-six com- plete cures, and eight deaths; six of these deaths occurred after subsequent ligature, the remaining two after amputation. In about one-third of the successful cases the cure was effected within twenty- four hours. Digital pressure can be made only with the aid of a considerable number of assistants, and it is usual to employ them in pairs, one making pressure while the other feels for pulsation in the sac. The skin should be covered with French chalk at the point where the pressure is made, and the assistants should be carefully instructed as to the amount of pressure needed and 405 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the place where, and direction in which, it should be made. When the change is made from one assistant to another, the latter should place his finger or thumb upon the artery immediately above or below that of the one whom he replaces, and this one should not remove his finger until after the artery is duly com- pressed by the other. Ether or morphine should be used u hen the patient begins to complain of the pain. (c) Compression by Esmarch's elastic bandage. This method was first employed in 1S75 by Walter Reid, of the British navy, in a case of popliteal aneurysm. The bandage was applied tightly to the leg, loosely over the tumor, and then tightly over the lower third of the thigh; then the cord was put on and the bandage removed. At the expiration of fifty minutes the pain had become so great that the cord was removed, two Carte's compressors on the upper portion of the femoral artery having been substituted. At the expiration of three hours from the commence- ment the aneurysm was found to be pulseless; inter- mittent pressure was kept up for two days, and then the patient was pronounced cured. The condition of the parts found at the death of the patient a few months later, and the method by which this treatment appears to effect a cure, have been described above. In January, 1881, Stimson collected sixty-two cases treated by this method, which may be grouped in three classes according to differences in detail. In the first class, fifty-two cases, Reid's method was followed ex- actly or very closely; in the second class, five cases, the rubber tubing or the elastic bandage was used repeatedly and alternately with the tourniquet or digital pressure to arrest the circulation for several hours; in the third class, five cases, the bandage was used for a short time daily for many successive days, without any compression of the artery in the intervals, or with a tourniquet loosely applied. In the first class there were twenty-eight cures, twenty-two failures, and two deaths; and of the cures twenty- four were obtained by a single attempt continued for about an hour on the average, the extremes of time being fifty minutes and three and one-half hours, and four by two attempts each, separated by an interval of from one to four days. After the removal of the bandage the artery was compressed with a tourni- quet or the fingers, usually for a few hours, but in one case for only one hour, and in another for five days. In two or three cases pulsation returned in the aneu- rysm on the following day, and was then definitely arrested by compression for a few hours. In twelve of the twenty-two failures the same method was used in nineteen different attempts; in the remaining ten with eighteen attempts, no pressure seems to have been made after the removal of the bandage. In at least five of the twelve the method was skilfully em- ployed, with every detail used in most of the success- ful cases; they show, therefore, when added to the twenty-eight cases treated successfully by this method, that it may be expected to fail in at least fifteen per cent, of the cases. As for the remaining failures, there is some reason to suppose that the method was not carried out with as much care and attention to details as it was in the others. A very important fact is that the method appears not to involve- any serious risk, and not to diminish the chances of success if resort is subsequently had to the ligature. Of the two fatal cases, in one the bandage Was applied twice with an interval of three days, and retained in the last trial for nearly eight hours. The patient died twenty-seven hours after- ward with symptoms of heart failure or shock, the dorsum of the foot remaining cold. In the other the aneurysm (of the anterior tibial artery) had ruptured externally, and amputation was strongly urged, but refused by the patient; gangrene of the foot and lower part of the leg followed, and the patient died dur- ing the second week. The circumstances in each i.i i- were quite exceptional. Bryant applied the bandage twice for three hours each time, with an interval of four days, in a case of popliteal aneurysm in a man forty-five years old. A fortnight after the second attempt he tied the femoral artery with catgut, the wound healed by immediate union, but "anemic gangrene" followed and the leg was ampu- tated. This is the only instance of gangrene in the sixteen cases in which the ligature was resorted to after the bandage had failed to produce a cure. The conclusion to be drawn from all these cases seems to be that we have in the elastic bandage an efficient means for safely shortening the duration of the treatment by compression of popliteal and some femoral aneurysms. The greater efficiency, the more speedy action of the method is apparently due mainly, if not entirely, to the arrest of the circulation through the collateral channels as well as through the main artery, thus securing absolute stagnation of the contents of the sac. Consequently the rubber tubing, which is drawn tightly twice or three times about the limb above the aneurysm, is to be deemed the efficient part; and the principal, perhaps the sole benefit from the bandage is that of making a less severe constriction by the tubing sufficient. The method of carrying out this procedure is simple: thus, in popliteal aneurysm, the bandage should be applied tightly to the leg, loosely over the aneurysm, and tightly again above it, and the bandage or the tubing should be kept in place for one or two hours; then the artery should be compressed by a tourniquet or the fingers for several hours afterward, the compression being occasionally intermitted for a moment to see if pulsation returns in the sac. If pulsation returns within a few hours, the artery must be again compressed. The introduction of needles or a coagulating injection might be proper in connection with a second trial after a failure. Matas {Annals of Surgery, vol. lii., p. 126) describes an elaboration of this test. (d) Compression by flexion of the limb. When an aneurysm is situated at the bend of a joint, pulsation in it may sometimes be diminished or arrested by flexion of the joint, and this fact has been occasionally utilized, either as the principal means of treatment or as an adjuvant thereto. The method appears to have been first suggested by Fleury, a French surgeon, in a paper published in the Journal de Chirurgie, in 1846, as an inference from his success in curing a wound of the brachial artery at the elbow by flexion. In 18.52 the suggestion was put into practice by Thierry in a case of traumatic aneurysm at the elbow, and in 1857 a large popliteal aneurysm was cured by flexion of the knee by Maunoir of Geneva. He tried at first to keep the leg forcibly Hexed upon the thigh, but the patient could not endure the pain, so he had to be content with keeping it partly flexed by a strap crossing the shoulders, while the patient went about on crutches. This was kept up about three weeks, at the end of which time the tumor had ceased to pulsate. Flexion has been used successfully in aneurysms of the popliteal artery, at the groin, and at the elbow. Of forty-nine cases of popliteal aneurysm treated by flexion, analyzed by Liegeois, twenty-six were cured, in eleven of which flexion alone was used, in eleven others flexion in combination with other means, and in four flexion after other means had failed. It \\:is first used at the groin by Gurdon Buck at the New York Hospital in an aneurysm which had recurred sixteen months after apparent cure by compression. Pressure on the external iliac did not arrest the pulsation, and flexion was tried as the only alternative lor treatment by laying open the sac. In a case of inguinal aneurysm treated by Eldridge, of Yokohama, a cure was obtained by keeping the thigh flexed upmi the pelvis for twenty days. In making use of the method it seems to be usually necessary to carry the flexion to a point at which it 406 REFERENCE HANDBOOK OF THE MFDH'W. SCIENCES Aneurysm, External markedly diminishes the pulsation in the tumor, ami perhaps arrests ii entirely, and then to keep the limb in tins position for a long time by suitable bandage oi apparatus. It is well, also, in popliteal aneurysm, to bandage the leg up to the knee to prevent swelling. The turrits of the method lie in the facility with u hich it can be carried out, and in the freedom from the chance of accidents if care is taken not to make too ible pressure. :>. Permanent arrest or obstruction of the stream on the distal side. By distal ligature (Brasdor's and Wardrop's methods). Distal ligature, firsl suggested by Brasdor and Desanlt toward the end of the eighteenth century, was first performed by Deschamps in 1798; the femoral v was tied in the middle of the thigh for the cure of a large aneurysm, the upper border of which was less than a finger's breadth below Poupart's ligament. As rupture of the sac threatened on the fourth day, the artery was compressed on the pubis, the sac opened, and the vessel tied above and below; the patient died eight hours afterward. The operation was next performed by Sir Astley Cooper, who tied the common femoral artery below the epigastric for a large aneurysm of the external iliac; the patient recovered from the operation, but the aneurysm continued to pulsate and soon afterward ruptured. In 1825 Wardrop obtained the first success, tying the < ommon carotid on the distal side of a large aneurysm in a woman fifty-seven years old. Wardrop's efforts to popularize the operation, and especially his extension of it to aneurysms of the innominate artery, have permanently associated his name with it as distinctive of that form in which the current is not completely arrested, but continues only through branches given off from the artery between the ligature and the sac; while the name of Brasdor is given to that form in which there are no such branches and the arrest of the current is complete. The operation is practically limited to aneurysms at the root of the neck, those of the common carotid, subclavian, and innominate. In some cases in which an aneurysm of the arch of the aorta has been mistaken for an innominate aneurysm, and the carotid and the subclavian in its third portion have been tied, marked relief of symptoms has followed, and in two or three cases the left carotid has been tied for recognized aortic aneurysm. The operation benefits by arresting or retarding the circulation in the vessel and sac and thus favoring the formation of a laminated clot. The anticipation that the pressure within the sac would be increased by the distal ligature has proved un- founded, and the first effect of the operation has often been an immediate decrease in the size of the aneurysm and in the force of its pulsation. The proportion of successes previous to the introduc- tion of the antiseptic ligature was very small, but with the introduction of this form of ligature the operation entered upon a new career of usefulness and of appli- cability to cases that had been beyond aid by surgical art. In eight cases of ligature of the carotid' and sub- clavian for innominate aneurysm in which catgut was used, death was caused by the operation in only one, and other successes have been since reported. Monod and Yanverts collected seventy-nine cases, the results being operative mortality S. 5 per cent., lasting improve- ment 60. S per cent., failures 21.7 per cent. It is, of course, less certain in its action than ligature on the proximal side, and its use will therefore be restricted to cases in which the proximal ligature or compression i* impossible or too dangerous — in other words, to aneurysms at the root of the neck, and perhaps of the external or common iliac. It is to be judged not by comparison of its proportion of successes with that of other methods, but rather as a grave alternative in a limited class of cases that are open to few other means of treatment, and that lead inevitably, if left to themselves, to prompt and certain death. Manipulation or malaxation of the aneur; This method, introduced by l erguson in L852 and employed twice by him, rests upon the same print as the distal ligature — arrest or diminution of the current by an obstacle placed upon the distal side of ac. In this method thi is a fragment of old clot mechanically displaced from the wall of the and lodged within the artery. This displacement of a clot is thought to be the mechanism by which many of the so-called spontaneous cures have been obtained. The conditions essential to its employ- ment are the presence of enough laminated clot in the sac to make the detachment of a piece of sufficient size possible and practicable by external manipulation, and the impossibility of safely resorting to other methods of treatment. The latter condition limits the method to a small number of cases, mainly those situated upon the subclavian artery. It is inapplicable to those situated upon the carotid, because of the certainty that small fragments will pass into the arter- ies of the brain and become cerebral emboli, with consequent paralysis. 4. Rapid coagulation of the blood in the sac, with or without temporary arrest of the stream. (a) Coagulating injections. This also is a method of very limited applicability, and is only mentioned for the sake of historical record; it can be used only as an adjuvant to other methods, or in exceptional cases, as of recurrence or of pouched aneurysms. Hydrate of chloral has been recently recommended. (6) Introduction of solid bodies. A few attempts have been made to induce coagulation of the blood in an aneurysm by permanently or temporarily introducing foreign bodies, such as wire, needles, horsehair, catgut. The method rests upon the well- known facts that, if freshly drawn blood is whipped with a bundle of fine rods, the fibrin collects upon them, and that firm clot forms upon a foreign body introduced into an artery or vein. With one or two exceptions these attempts have been made upon aneurysms that were not open to treatment by any of the methods of ligature or compression, such as aneurysms of the aorta and subclavian. The first case of permanent introduction was that of Mr. Moore; the first of temporary introduction of needles, those of Rizzoli and Malago. All these methods are obso- lete to-da3 7 and have been replaced by the Moore- Corradi method of introducing gold wire into the aneurysm and performing electrolysis. Good reports have been given by Lusk,Stuart, and Finney (Annals of Surgery, May, 1912). (c) Galvanopuncture. In this method the con- stant galvanic current is employed to produce rapid coagulation of the blood in the sac. The details of the operation, as employed in different cases, vary greatly. Most operators will to-day prefer to use the wiring method already referred to. 5. Promotion of the formation of a laminated clot by irritation of the wall, "needling." This, recently introduced by Macewen, has led in a number of cases to marked reduction of the symptoms and even apparent cure. A long, stiff needle is pushed through the sac until its point reaches the opposite side where it is moved to and fro so as to scratch the surface. By changing its direction several areas may be thus irritated without withdrawal and reintroduction of the needle. Traumatic Aneurysm, and Rupture op an - Ar- tery. — A traumatic aneurysm is one which owes its formation to a wound of the artery that has divided all its coats, or to an injury (stretching, bruising) that has divided one or more of them. The common cause is a penetrating or punctured wound; less common causes are overstretching in the neighborhood of a joint and fracture. The continuity of the artery is usually not entirely destroyed, and while some of its blood escapes into the adjoining tissues the remainder 407 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES continues within it and is distributed through its branches. The effused blood is in part absorbed, and in part coagulates; and after a time a distinct sac forms about it, by condensation of the tissues, and it then differs in no essential way from the com- mon encysted form of aneurysm. Its symptoms and it- subsequent course are then the same, but during the stage of formation of the sac the condition is associated with dangers peculiar to itself. There is the history of the injury, absence or diminution of pulsation in distal branches, local swelling and ecchymosis, and sometimes marked lowering of the temperature of the limb. There is usually a bruit but no pulsation in the swelling at first, but, after the sac has formed, the expansive pulsation charac- teristic of an aneurysm is present. During the formative stage of the sac the injury is peculiarly amenable to treatment by direct pressure at the seat of injury; and often after the sac has formed a cure may be effected by the same means. This is the one important practical point of difference between traumatic and spontaneous aneurysms. When the injury is associated with fracture of a bone the immediate treatment, unless the symptoms are very alarming, should be confined to securing the repair of the fracture and to limiting the extravasa- tion of blood by suitable pressure, and the treatment of the aneurysm should be postponed, if possible, until after the bone has united. The presence of the extravasated blood is not a serious obstacle to this repair, while the conversion of the fracture into a compound one by an incision made to secure the wounded artery may have very serious consequences. Exceptionally, the extravasation may be so free as to endanger the vitality of the limb by its interference with the circulation, and under such circumstances the surgeon may be compelled to turn out the clots and secure the vessel, or even to amputate. This is much more likely to be the case in complete rupture of the artery, when none of the blood brought by the artery is carried past the injury into its distal branches, but all is poured out into the tissues, and, being bound down by the enveloping fascia, exerts a pressure which checks the venous flow and prevents the establishment of collateral circulation. This con- dition is characterized by great and uniform swelling, absence of pulse, and notable loss of temperature in the limb. Arteriovenous Aneurysm. — When an abnormal direct communication is established between the trunk of an artery and that of a neighboring vein, the condition is known as an arteriovenous aneu- rysm. When the two vessels remain in close con- tact, and the blood passes directly from the artery into the vein, the variety is known as aneu- rysmal varix, the prominent feature being a varicose dilata- tion of the vein. When, on the other hand, an aneurysmal pouch is formed by condensation of the adjoining tissues, the variety is known as a varicose aneurysm, or as an arteriovenous aneurysm in the narrow sense. In the great majority of cases of varicose aneurysm the aneurysmal sac is intermediate between the artery and the vein, and blood passes through it on its way from the former to the latter. Broca describes a sub-variety, in which the artery and vein communicate directly with each other and there is an aneurysmal pouch lying on the opposite side df the artery. Probably tile distinction could not be made during life. In some of the classi- Fig. 23S. — Arteriovenous Aneurysm. (Bell.) fications any case that presents a distinct aneurysmal tumor, whether enclosed by a sac of new formation or by one formed by circumscribed dilatation of the vein, is called a varicose aneurysm; but the latter variety, that in which the aneurysm is formed by dilatation of the vein, seems to be much more closely allied in every way to aneurysmal varix. The common cause of this affection is a wound involving both the artery and the vein; but in some cases the communication forms by ulceration of the wall of the vein where it is pressed upon by an aneu- rysm, and in one case (reported by Pemberton in Med.-Chirurg. Trans., vol. xliv., p. 189) an arterio- venous aneurysm formed at the groin ten months after prolonged instrumental pressure had been made at that point to cure a popliteal aneurysm. The most frequent cause by far, in the past, has been the wounding of the artery in venesection at the elbow. The usual cause in recent times is a gunshot or stab wound. Another occasional cause is fracture of the base of the skull, by which the carotid artery is torn in the cavernous sinus. Spontaneous forma- tion by rupture of an aneurysm into a vein i.s rare, and almost confined to thoracic and abdominal aneurysms. The 'pathological changes which are found in this class of aneurysms vary greatly in their details, according to the character and extent of the primary injury and of the communication between the vessels, and to the distance of the vessels from the heart. The principal factor in the production of these changes is the extent to which the intraarterial pressure is transferred to and exerted upon the wall of the vein and the aneurysmal sac; and this is determined by the size of the opening in the artery and by the resistance offered to the return of the blood through the vein to the heart. Hence, when the communication is be- tween an artery and a large venous trunk, such as the internal jugular, which can readily carry away the excess of blood almost as rapidly as it is supplied, the distending force is not much exerted and the obstruc- tive changes in the vein are slight; but when the communication is between an artery and a vein in one of the extremities, or in the head, an immense aneu- rysmal pouch may be formed or the veins may become greatly dilated and varicose. The pouch usually has a smooth internal surface and contains little or no stratified clot, and when it is formed in great part by dilatation of the vein, the orifices of other veins open- ing into it are seen at various points, and these veins are enlarged and their walls thickened. The artery below the point of communication is smaller than normal, and if it has been entirely divided by the original injury, the lower portion may be occluded at the point of division; the end of the upper portion is kept open by the stream of blood. The symptoms vary somewhat with the pathological changes; there may be a well-defined pulsating tumor, presenting the usual features of an aneurysm and the special ones peculiar to this variety, or there may be simply a diffused swelling of the region, or the super- ficial adjoining veins may be markedly varicose. The special features are the bruit and the thrill. The bruit is continuous, with a systolic reinforcement: it is most intense immediately over the point of commu- nication between the vessels, and becomes less, or may be changed into an intermittent murmur, as the distance from this point increases. This apparent intermittence is due simply to the fact that the por- tion of the murmur which corresponds in time to the contraction of the heart is louder than the rest, and is heard at, a distance at which the latter has become inaudible. In some cases the murmur could be heard at a great distance along the vessels; thus in one quoted by Follin, it could be heard from the elbow to the heart; in another (of the femoral), from the head to the feet. The thrill is a peculiar sensation given to the hand when laid upon the aneurysm, a vibration that has been compared to the purring of a cat. 408 KKIT.KKMT. HANDBOOK OF Till: Ml. UK AL SCIENCES Ani-ur; -in. External The interference with the circulation below the point of communication is commonly well marked, and i- shown by swelling of the limb which is not edema, but which, in some cases at least, i- an actual hyper- trophy, and is accompanied by a permanent elevation of i he temperature of the limb, by a greater growth of hair upon it. and in one case by an increase of an inch in lengl h. There is a feeling of numbness or of act ual pain in the limb, increased by its use, and there may be a marked loss of muscular power, and sometimes persistent ulcers or eczema. The lesion may fail to become apparent until some- time after the receipt of the injury (four years in one case), and commonly it remains stationary after havin.s reached a certain development. Thus,, situ- ated upon the great vessels, the carotid and internal jugular for example, seldom cause any inconvenience he patient. In a few cases the opening into the vein has closed spontaneously, and the aneurysm has been thus transformed into a simple arterial one. Treatment. — In recent cases carefully graduated. direct pressure has sometimes availed to close the opening, and this may be aided by compression of the artery above. Operative interference in the past, which has included a variety of methods, has proved exceptionally dangerous, but the statistics for obvious reasons have lost much of their value with the improve- ment in operative methods and in the treatment of grounds. The operations may be divided into two main classes, according as the sac is or is not opened, and in the latter class they will further vary accord- ing to the number of the ligatures applied. The question of interference will be determined by the extent of the disability and the number of vessels involved in the lesion. In the forearm or on the scalp it is usually practicable to tie all the vessels, arterial and venous, that are involved, and thus effect a radical cure. In the neck (carotid and jugular) the history of recorded cases shows that the lesion rarely causes more than a moderate amount of inconvenience that can be easily borne by the patient. Ligature of the artery alone on the proximal side, in arteriovenous aneurysm of the lower extremity, has proved remarkably fatal by gangrene. In twelve cases collected by Van Buren, the external iliac was tied in five and the common femoral in two and gang- rene followed in all; the femoral was tied in five, and ;rene occurred in two. Monod and Vanverts cite eighteen cases with only thirty-eight per cent, of successes. This extraordinary frequency is presum- ably due to the easj' return to the heart, through the opening into the vein, of the blood brought to the distal segment of the artery by the collateral branches; it fails to pass on and nourish the limb. Consequently a second ligature applied to the artery close below the opening, diminishes the chance of gangrene. Ligature of all the veins, as well as of the artery, suppresses all subsequent growth of the sac or continuance of the disease, but it adds a factor that is most important in the production of gangrene — obstruction of the venous flow. Moreover, the operative difficulties are extreme. The record of cases in which the sac has been opened and the attempt made to arrest all bleed- ing from it, is such as to discourage any one from undertaking it; again and again operators have had to resort to ligatures en masse, passed by means of curved needles, and more or less blindly, in deep, inaccessible corners of the wound, to the actual cautery, and even to styptics and pressure. The incision has always been very long, and the tissues have been bruised and lacerated by the prolonged search and dissection. The method seems to violate all the principles that govern modern methods of making and treating wounds, and it does so, in the effort to attain an end that is not only unnecessary, but introduces an element of great additional danger. Monod and Vanverts found that quadruple ligation of the vessels resulted in gangrene three times out of fifteen, while incision or extirpation nf the sac gave such a result in only two out of one hundred and seventeen cases. A few successes have been obtained by galvano- puncture and by the inject inn oi coagulating solutions without ligaturing any vessel, and quite recently, in a few cases in which the changes were not very ex- tensive, the sac has been successfully extirpated. Cirsoid \\i i rysw (arterial varix; aneurysm by anastomosis). — This name ha- been given to an affection of the arteries, sometimes involving also the capillaries ami even the derived veins, which differs materially from that which constitute- the common variety of aneurysm, and i- characterized by a uni- form or irregular dilatation and to Ilgthening of an artery and its branches. The affection is mo I common in the superficial arteries of the head — the temporal, occipital, and auricular — but it is also found in the hand, forearm, leg, and even involving the ex- ternal iliac artery. The change consists in a dilatation and lengthening of the artery, with atrophy of its middle coat and consequent thinning of the wall, or possibly with hypertrophy by thickening of the middle coat in the early stages; the dilatation may make the caliber of the vessel ten time- larger than normal, and may Ik; uniform, but is usually accompanied by the formation of small pouches. In consequence of the lengthening the artery assumes a tortuous form. The change has a marked tendency to spread in both directions, in- volving the arterial branches and even the consecu- tive capillaries and veins, and in the latter case it is known as aneurysm by anastomosis or racemose ant urysm. There is also reason to think that in some cases the change has originated in a nevus and has spread backward to the arteries. At the central portion of the tumor, where the tortuous and dilated vessels are most numerous and closely packed, there may exist, as Lefort has pointed out, a sort of central lake, as in cavernous angioma, or a real aneurysm or even an arteriovenous aneurysm. The overlying skin and soft- parts may be thinned, or thickened ami indurated, and the underlying bone may be absorbed in consequence of the pressure. The principal causes are found in contusions and preexisting erectile tumors or birth-marks, and the change takes place most frequently at the time, or shortly after, the age of puberty is reached. In w hat manner or through what agency these causes act is not known, nor why the region of the head is the common -cat. Blake and Auchencloss in a study of the etiology and pathology of cirsoid aneurysms ascribe trauma as a frequent cause, and emphasize the fact that they tend to extend centripeally, i.e. toward the heart. Some of the microscopic findings show ap- pearances somewhat resembling conditions seen in a dissecting aneurysm. (Medical Record, June 24, 1011.) The symptoms of the disease are a soft, ill-defined swelling under the skin, in which numerous pulsating vessels can be felt, and into which tortuous arteries can be seen to pass. The overlying skin is reddened or livid, either by implication of its own minute ves- sels or by transmission of the color of the blood below it; the tumor communicates a sort of thrill to the hand, and a continuous murmur to the ear. In a complete typical case four distinct varieties of changes or lesions can be recognized: First, a cutaneous erectile tumor, formed by dilatation of the arterial capillaries of the skin; second a subcutaneous arterial cir-oid tumor, formed by the dilatation of the finest arterioles under and around the first ; third, dilatation and tortuosity of the main arteries leading to the tumor; fourth, dilatation of the veins coming from the tumor, sometimes with pulsations S3 r nchronous with those of the heart. The affection is a serious one, because of its tendency to increase and the danger of hemorrhage through ulceration of the skin or an accidental injury. 409 Aneurysm, External REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Treatment has generally proved not only difficult, bloody, and dangerous, but also unsatisfactory as re- gards the cure of the disease. It comprises ligature of the main trunks from which the affected arteries arise, as of the temporal, or the external or common carotid, in cirsoid aneurysm of the scalp; excision or incision of the tumor; caustics; galvanopuncture and coagulating injections, or extirpation of the main trunk leading to the aneurysm, this latter not being touched at all. A suitable case is an aneurysm of the temporal region cured by excision of the external carotid to its bifur- cation into the internal maxillary and temporal arteries (Blake and Auchencloss, Medical Record, June 24, 1911). Lefort, who made a careful study of eighty- three cases, says that whenever treatment has been directed only to the afferent arteries, it has failed or has produced only an incomplete cure; but that, on the other hand, the obliteration of the vessels forming the central portion of the mass has been followed by the return of the afferent vessels to their normal con- dition. He claims, therefore, that the treatment should always be directed to this central portion. It in- cludes three methods: removal or destruction of the mass by caustics or the knife; the injection of coagulat- ing liquids; galvanopuncture. Removal by the knife exposes to severe hemorrhage, but, if practised with caution, is practicable and to be recommended when the central mass predominates. Destruction by caustics (chloride of zinc) seems to be without much danger of hemorrhage, but is slow and tedious and may cause superficial necrosis of underlying bone. Lefort recommends the injection of a solution of the perchloride of iron, which has given nine successes in ten cases; he prefers a five-per-cent. solution to the stronger ones. John Duncan refers to four cases treated by electrolysis, three of them successfully. The variety known as aneurysm by anastomosis, in which the capillaries and veins are also involved, is less amenable than the others to this method of treatment. Dissecting Aneurysm. — This is a lesion occas- ionally found in the aorta, which has only a patho- logical interest, since it cannot be recognized with certainty during life and is not open to treatment. It consists of a partial rupture of the wall of the vessel, and the passage of the blood between its coats, usually in the substance of the middle coat, to a second opening into the lumen of the vessel at a lower point, or backward to one into the pericardial sac. The primary opening is usually in the arch of the aorta; the second one may be in the same vessel, or at a considerable distance in one of its branches — once in the subclavian, once even in the popliteal. When the flow is backward into the pericardium, death promptly follows; in other cases the period of survival is usually short, but may be prolonged for years, and under such circumstances the track followed by the blood develops a resisting wall lined with epithelium. Lewis A. Stimson. Charles L. Gibson. Aneurysm, Internal. — Etiology and Pathology. — In this article no attempt is made to discuss at length the etiology and pathology of aneurysm in general. It is intended rather to present in as con- densed a form as possible the principal points bearing upon the diagnosis and treatment of the internal form of the disease. Age. — Aneurysm may occur at any age but it is most frequently found in the decade from thirty to forty and next from forty to fifty. In children and adolescents it is extremely rare and usually results from an infected embolus, or in some instances from inherited syphilis. Aneurysm becomes less frequent with advancing years, and is then usually associated with atheroma. Sex. — Men are mi ire liable to the disease than women. Peacock states that from two-thirds to four-fifths of the cases of circumscribed aneurysm occur in males while Crisp's extensive figures show a ratio of five to one. The difference is no doubt to be accounted for by the fact that men are much exposed to the efficient promoting causes, viz., strain, laborious occupation syphilis, and intemperance. In dissecting aneurysm the sexes are attacked with almost equal frequency. The development of the disease is favored by a high blood pressure, but weakening of the arterial wall plays a far more important role in the morbid process. It is particularly apt to develop from inflammatory processes in the media, resulting in most instances from syphilis, but occasionally due to rheumatism or other infections. The influence of syphilis as a cause of aneurysm is now very generally admitted, and evidence of pre- vious luetic infection occasionally gives an important clue to the diagnosis of obscure abdominal or thoracic aneurysms. From forty to eighty per cent, of cases are usually attributed to this cause, and some writers give even a higher percentage. The syphilitic lesions are usually very limited in extent, consisting in patches of mesarteritis, of an inch or less in diameter, with furrowing and scarring of the intima, occurring most frequently in the ascending aorta. Remnants of these patches may be found at the orifices of an aneurysm and their specific character has been proved by the discovery of the spirochete. An important con- firmation of the influence of syphilis is found in the Wassermann reaction. The figures available are still somewhat meager, but Steinmeier has been able to collect sixty-five cases of aneurysm, of which seventy-five per cent, gave a positive reaction, while several negative cases presented indubitable evidence of the disease. Other infections play a recognized but infrequent part in the causation of aneurysm. Acute rheumatism typhoid fever, pneumonia, influenza, and septic processes frequently lead to degeneration of the intima and, what is of much more importance, to patches of inflammation with subsequent necrosis in the media; these areas when yielding to the blood pressure result in aneurysmal dilatation. Embolomycotic aneurysms, found chiefly in malig- nant endocarditis, and only in rare instances following immediately on other infective processes, seldom attain a larger size than a walnut. They occur most frequently in the superior mesenteric, the cerebral \ essels, and t he aorta, but the visceral arteries, as well as the iliacs and peripheral vessels are occasionally involved. Often occurring at an earlier age than the chronic form of the disease, and frequently multiple, they seldom attain a size larger than an egg, and usually terminate rapidly by rupture and hemorrhage. Lewis and Schrager state they most commonly origi- nate in the intima from the lodging of infected em In > 1 1 at tlie bifurcation of arteries, and less seldom in the media through bacterial invasion by the vasa vasorum. Mechanical injury of the arterial coats by a sharp pointed embolon is now regarded as unusual, and the infective origin as much the more usual method of production. Traumatism. — Since blows or violent straining efforts especially in muscular men are sometimes sufficient to tear the intima and a portion of the media, the greater frequency of aneurysm in the laboring classes is, at least in part, to be attributed to the influence of strain and effort. The tear commonly begins over atheromatous plaques, but a healthy artery may suffer as in the case related by Busse (Virchou's Areliiv, 1S3). The tear may lead to a saccular aneurysm, or in rare instances to a dissecting aneu- rysm. Adami has pointed out the frequency with which the latter form is associated with hyaline athero- matous areas in the aorta. Severe, sudden pain marks t he mi -el of the tear and later the development of aneu- rysm or a rapidly fatal termination from hemorrhage may occur. 410 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aneurysm, Internal Atheroma is the common cause of aneurysm in elderly people, and is less seldom responsible in earlier life. There is no apparent relation between the extent of atheroma and the development of irysm and most extensive lesions are extremely common without the slightest tendency to aneurysm. ious conditions leading to atheromatous dogenera t ion, such as alcoholism, lead poisoning, and gout, Elay some part in the production of aneurysm, and the igh blood pressure, so frequently present, also - the development of the malady. Site. — The most frequent site is on the ascending aorta. In Hare's statistics 570 out of 953 case oi aortic aneurysm involved this portion of the vessel, while the transverse arch was affected in 104 and the descending arch in 110 instances. The abdominal aorta suffers much less frequently than the thoracic, the ratio being as one to ten. In the great majority idominal cases the aorta is involved at or near the celiac axis and the lower portion of the aorta is seldom attacked. In Nixon's tables (St. Bartholomew's Hosp. Hep., 1911), it is suprising how seldom an- eurysm is found except at or in the immediate neigh- borhood of the celiac axis. The arteries arising from the aorta often share in the aneurysmal process, and are less commonly affected alone. These vessels, however, and also the cerebral ics are involved in a considerable number of cmbolomycotic aneurysms and also in those some- what rare cases from acute infections. Sacculated aneurysm is by far the most common form. In Hare's figures there were 544 instances and only twenty-six fusiform in the ascending arch. Dissecting aneurysm is a rare type. Adami has shown that it occurs in almost equal number in the two sexes, and that it is frequently found associated with gelatinous hyalofibrinous plaques; the blood passes in a channel between the coats of the vessel of which the inner wall is formed by the intima and part of the media. This channel commonly begins in the ascending arch and may extend along the whole length of the aorta and even along the iliacs as in a of Field's. The lining of the sac is often smooth and gives at first sight the impression of a double tube, while the branches may spring from the sac or from the vessel itself. The onset of these cases may be marked by sudden violent pain which gradually subsides as the stretching due to separation of the arterial wall subsides. The subsequent course is variable; rupture followed by hemorrhage with a rapidly fatal termination is frequently found, but in a few instances the process becomes chronic and the condition may last for years. Thoracic Aneurysm*. — Symptomatology. — The existence of a dilatation at some part of the aorta is not necessarily accompanied by manifestation of disordered function or local distress, that is to say, by symptoms. Unless, therefore, it mechanically in- terferes with neighboring parts, it may continue even for a long time unsuspected. The occurrence, then, of symptoms which will indicate the existence of thoracic aneurysm, depends more upon the exact situation of the tumor than upon any other circum- stance. The symptoms also will present wonderful variety in accordance with the varying locality and direction of the expansion of the growth. The clinical history of these patients previous to the de- velopment of the characteristic symptoms is often ex- tremely indefinite. It is quite common to find a man seeking advice for a loss of voice or a harsh cough, or a thoracic pain, found to be due to an aneurysm of some standing, and yet he will give an account of having enjoyed excellent health in every respect * The article on Thoracic Aneurysm by the late Dr. George Ross, in the previous edition of the Reference Handbook, remains as written, with but few alterations. — F. G. F. until (perhaps quite recently) these symptoms attracted his attention. Again, sometimes a quick pain, wit 1 1 palpil at n in and breathle tti has been observed at some remote period, to be followed later OD by other symptoms of intrathoracic disorder. Or, some laryngeal or bronchial symptoms may ha ■ b i a coming on imperceptibly for a long time pa In many cases, belonging to one of the above types, of men about middle age, whose general health and nutrition remain unimpaired, suspicion of aneurysm may very reasonably be entertained. Deepseated aneurysms may be entirely latent, presenting no evidence of their existence by either .symptom or physical signs. The comparative frequency of such cases is now being very generally recognized. The symptoms of thoracic aneurysm, therefore, are mainly the symptoms of intrathoracic pressure, and mostly differ in no respect from those produced by tumors ol different nature in the sa sit nation. The symptoms consist of the manifestations by which we ■ •an recognize displacement of lung substance, con- pression of the main or secondary air tubes, irritation or destruction of nerves, obliteration of venous channels, obstruction of the esophageal tube, or erosion of some of the bony structures. The principal symptoms of intrathoracic pressure may be thus enumerated — pain, dyspnea, altered voice, cough, stridor, headache, and disordered vision, and lastly, paraplegia. The pain of thoracic aneurysm is a most frequent symptom, but very variable as to its character, degree, and situation. In not a few cases pain of some kind will be the first indication of existing disorder. Early pain is usually of a somewhat lancinating nature, and is suggestive of neuralgia. It is often complained of as darting across some region of the chest or along certain nerves to distant parts. When the aneurysm, for example, is seated in or near the innominate artery, the pain is often referred to the back of the neck on the right side and behind the right ear; when it is seated in the transverse arch, the pain may be across the top of the chest and down perhaps the entire length of one arm. Pains of this kind should always prompt a search for internal aneurysm. Later on in the complaint the pain is likely to be of a steady, wearing kind, and referred to some fixed spot, probably deep in the chest. Aneurysms pressing backward against the vertebral column and the spinal nerves emerging therefrom have two special forms of pain connected with them: either a persistent boring pain experienced in some particular part of the spinal column, or a definite intercostal neuralgia, having a distributive, intermittent character, and tender spots often unusually well marked. There is sometimes pain of a real anginoid character, ac- companied by a sense of tightness in the chest, but it is very seldom that attacks of true angina, with the typical features of this complaint, are witnessed. Pressure on the phrenic nerve has been found some- times to be accompanied by a painful feeling of con- striction round the lower part of the thorax, together with dyspnea and singultus, from disturbed inner- vation of the diaphragm. Dyspnea is a very frequent symptom, and is of vary- ing character and degree in accordance with the cause to which it may be due. It may arise from compression of a portion of the pulmonary structures, from pressure upon the trachea, upon a main bronchus, or upon the pneumogastric trunk or one of the recurrent nerves. An aneurysm must have attained to a considerable size before it can shut off a portion of a lung sufficient to produce decided dyspnea. .Shortness of breath, therefore, will not be much complained of in the early stages, unless the tumor interferes with some of the other stuctures just named. Compression of the tra- chea commonly occurs from aneurysms of the arch, and the dyspnea will be observed toexist both in inspiration and in expiration. It is accompanied by enfeeble- 411 Aneurysm, Internal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES menl of the respiratory murmur in both lungs, and the laryngoscope shows the mechanism of the vocal cords to be normal. Under favorable conditions a skilled irver can detect the narrowed lumen of the trachea by the laryngoscopic mirror, and in some instances can even observe pulsation transmitted from the aneurysm at the point of pressure. Standing beside such a patient, it is quite usual to hear a rough, raucous sound of peculiar caliber accompanying both inspiration and expiration, especially when these acts are performed somewhat forcibly. The dyspnea here, as in the last-mentioned form, is very markedly increased by even slight exertion, the chief reason, no doubt, being that the tumor, being expansile, the in- creased heart's action expands it, and causes it to compress the elastic tube more firmly. In exceptional cases of tracheal compression, paroxysms of intense dyspnea may be occasionally witnessed, and that without direct involvement of any of the important nerves. Attacks of this character are apt to come on from exertion or emotional disturbance, and are attributed by Bristowe to more or less complete ob- struction of the trachea by a plug of mucus. Position will often relieve the respiratory distress considerably, and patients very frequently, of their own accord, rest or sleep, leaning the chest well forward to take off the pressure from the windpipe. If a main bronchus be compressed (and it is more often the left), the dyspnea is not likely to be so great, and enfeebled breathing is found in the corresponding lung. It has long been recognized that pressure upon the impor- tant nerves supplying the muscles of the larynx which pass through the chest will cause dyspnea and that, very often, of the most intense kind. Here the striking feature is dyspnea in paroxysms. There may be periods of comparative calm, during which there is only a moderate shortness of breath on making some exertion, but suddenly, with or without any exciting cause, severe suffocative dyspnea sets in, and in some cases actually proves fatal. This result may be brought about by either the compression or involve- ment of a pneumogastric nerve or a recurrent laryngeal nerve. Sometimes nerves of both sides are implicated. ( hving to its situation in relation to the aneurysm, the nerve of the left side is more often affected than that of the right. When the latter is involved, it is generally from its being disturbed by the dragging of a tumor upon the root of the right subclavian artery. It is held by some that this form of dyspnea may be brought about either by spasm of the muscles supplied by the recurrent nerve or by their paralysis. Pressure, it is said, will either irritate or destroy a nerve. Irritation will cause spasm, destruction, paralysis. There does not, however, seem to be any reliable evidence of the occurrence of spasm as a cause of dyspnea; while, on the other hand, whenever decided laryngeal symptoms are observed from intrathoracic pressure, the laryngoscope nearly always shows the ex- istence of paralysis in a greater or less degree. Uni- lateral paralysis may exist for a long time without marked dyspnea, but, if the opposite muscles become affected, the liability to paroxysmal attacks becomes developed, the flaccid cords are sucked together by the inspiratory effort, and a suffocative condition is induced. Why does this occur in paroxysms? It may be that a rapid temporary enlargement of the tumor occurs (from exertion, etc.), and that this causes increased pressure, as a result of which the paralysis may be rendered complete; or it may be that, from incomplete coughing efforts, mucus collects in the glottis, and forms a complete' barrier in the already partially obstructed glottic opening. A rare form of dyspnea in aneurysmal patients consists in a sim- ulation of ordinary asthma. I have seen one such case in a young unman in which the picture pre- sented was exactly that of a common attack of spasmodic asthma. All/rations of voice are observed only when the tumor presses upon one of the recurrent nerves, or upon a pneumogastric trunk. The changes in the voice consist mainly in diminution of its power and clearness in varying degree, together with hoarseness and sometimes a squeaky or high-pitched tone. The loss of voice may come on quite suddenly, and ultimately complete aphonia may result. These laryngeal symptoms may be among the very first complained of, thus simulating catarrhal laryngitis, for which this condition has frequently been mis- taken. Laryngoscopic examination almost invari- ably shows deficient abduction of a vocal cord (more frequently the left). If the paralysis be incomplete, the affected cord is seen, on phonation, to fail to reach the median line, and thus an open space is left between the two. If it be complete, the paralyzed band remains almost, if not quite, stationary, and the healthy cord is seen to move rapidly across the median line until it approaches its fellow of the opposite side. Stridor is specially noticed when an aneurysmal tumor presses upon the trachea or one of the main bronchi. It differs altogether from the stridulous. respiratory sounds heard in cases of laryngeal disease, and is distinguished also from them in that the ordinary speaking voice remains unimpaired. The stridor is usually a rough, low-pitched, growling sound, accompanying both inspiration and expiration, and giving the impression of originating deep within the chest. It is markedly increased by full breathing. This is the so-called "stridor from below" of the older authors. Cough very commonly occurs during the course of a thoracic aneurysm. It is produced mainly by the irritation from pressure of the pulmonary and laryn- geal nerves, and is often very frequent and distressing. If there be laryngeal paralysis the cough will proba- bly be husky, and even suppressed. When tracheal pressure with stridor exists, the cough becomes dry and harsh. A peculiar ringing, brassy, croupy, cough is very suggestive of aneurysm. The expecto- ration at first is very small in quantity — in fact it may be so throughout; but when there has been much pulmonary irritation, or when a tracheo- bronchial catarrh has been set up, large quantities of purulent expectoration may be got rid of. Blood sometimes appears in the sputum, and must always be looked upon as a sign of impending danger. Dysphagia is a symptom more often seen in con- nection with other forms of intrathoracic tumor than with aneurysm. It has also been clearly proven that an aneurysm may have exerted considerable pressure upon the esophagus and yet no resulting dysphagia will have been observed. Certain pecul- iarities in esophageal obstruction due to aneurysm (as compared with that which results from other tumors or from organic stricture) are these: that it is variable — perhaps at one time of day nothing can be swallowed, and again, later on, fluids or semi-solids pass with comparative ease; and, secondly, it is altered by position — the patient may be able, by removing the weight of the tumor on leaning well forward, to swallow fairly well, while the same thing is impossible in the recumbent position. Engorgement of the vena cava and its branches, from pressure of the sac upon this great trunk or upon one of the innominate veins, occurs pretty frequently. It is indicated in the lesser degrees by undue fulness of certain of the superficial veins of the neck, shoulder, and front of the chest. In an extreme degree the appearances produced are very striking. The face is purple and congested, the eyes are suffused, the superficial veins greatly distended with blood and mostly tortuous. The tissues at the root of the neck become infiltrated and present a soft, swollen appear- ance, obliterating more or less the hollow above the clavicle. The congestion of the internal veins, which must simultaneously occur, causes these 412 REFERENCE HANDliOOK OF Till: MEDICAL SCIENCES Aneurysm, Internal patients to suffer from headache and often from great drowsiness, ami death may take place in a natose condition. Pressure mi the brachial veins will cause swelling of the corresponding arm. rence in the Size of the Pupils. — The anterior roots of the spinal nerves from the sixth cervical to the sixth dorsal (according to Brown-Sequard to the ointh or tenth dorsal) supply the cervical sympathetic filaments which pass to the iris. When an aneurysm presses upon these nerves, then ocular symptoms arc i veil, more or less marked according to t lie degree of the pressure. If the pressure is slight, then irrita- tion only is produced and. as a consequence, there itationof the corresponding pupil. If the pressure i- considerable, then paralysis is produced, and we find permanent cunt raction of that pupil, occasionally associated with enophthalmos and slight drooping of the lid. With reference to this symptom, it must be loped to a decided degree before any reliance can I upon it, because the slighter differences in between the two pupils are quite commonly rved in healthy persons. Even when this symp- tom is clearly made out its importance is not great from a diagnostic point of view, for there an- generally then present many more reliable indications of bhe disease. But it can be used as one means to assist in enabling us to locate more precisely the seat of the tumor. The Argyle-Robertson pupil is occasionally noticed and is to be regarded as a post-syphilitic imenon. is very often wanting, and persons with large tumors may remain quite well nourished. Con- siderable emaciation is, however, often seen arising from coincident weakness of * ho digestion, want of exercise, and continued suffering. Marked wasting of the tissues has in rare cases, been traced to pressure upon the thoracic duct, and again, although it develops less rapidly, to pressure upon the esophagus and to inanition. Such are the chief symptoms of thoracic aneurysm, which are the result of the intrathoracic pressure which it must sooner or later produce, and it is to them we must generally look for aid in establishing a diagnosis. But there are others which must be mentioned. It sometimes happens that the objective - of aneurysm may be present while subjective symptoms are entirely wanting. But the contrary is more generally true. Various complaints will be made before the existence of their cause can be satis- factorily made out. .Much, of course, will depend Upon the situation of the tumor. Patients often first experience pains in the chest, the different charac- ters of which have been already alluded to. As the tumor increases in size these painful sensations may be modified in various ways by the occurrence of complicating inflammations of surrounding parts, and especially of the pleura. There may also be a distinct sensation of throbbing or pulsation in the chest in the region of the aneurysm. Palpitation of the heart and tightness in the chest are often associ- al 1 with these. The patients themselves may also observe that alterations of position have an effect in increasing or diminishing their discomfort. Then dyspnea of some kind is likely to occur and to be followed by dysphagia, neuralgias, pareses, or actual paralysis (perhaps only formication or numbness), some anemia, diminution of strength, and sometimes edema. An aneurysm of the chest may thus cause death by a gradual process. Less commonly we observe continuous increase in the tumor until it finally ruptures and death ensues, either directly from hemorrhage or indirectly from the effects of the effusion of blood upon some vital organ. Rupture is generally associated with enormous hemorrhage, which is inevitably fatal in a few minutes or seconds. It does happen, however, that smaller bleedings occasionally make their appearance for some time n may be for only a day or even for a longer time) previous to the final gush. In the case of a gentle- man, under the care of the writer, who died of this disease a short time ago, small quantities (a few ounce-) of bright arterial blood were brought up for more than twenty-four hour- pi. -ceding the actually udden end. In this case the aneurysm broke into the substance of the lung, and evidently had leaked into a small bronchus during the time mentioned. The final rupture took place into the left main bronchus, and was accompanied by a great spirt of fluid blood, and followed by instant death. Hemop- tyses sometimes occur at long interva aneurysms, generally from associated pulmonary conge tions. When rupture take place, it may be accompanied by a sense of tearing within the chest, and if the blood does not appear externally With cough or efforts of vomiting (through the trachea or through the esopha- gus), then it will be recognized by the accompanying pallor and syncope, with failure or extinction of the pulse. Internal rupture takes place most frequently into the pericardium, and is almost always immedi- ately fatal, although in a case quoted by Kelynack the patient lived for four hours. Pepper and Griffith have published a ease of rupture into the superior vena cava, and they have collected twenty-seven other instances, while Fr&nkel has recorded two such accidents recognized during life. The symptoms are dyspnea, followed by slight proptosis, and by edema and cyanosis of the face, neck, upper part of the thorax, and arms. There is frequently a continuous murmur, louder during systole and produced by the passage of blood from the aorta into the vena cava. 1 leath in such cases is not necessarily immediate, and has been postponed for several weeks or months after the occurrence of the rupture. Escape into a pleural cavity is common, and is marked by severe pain and dyspnea, and by the presence of the physical signs of effused fluid. I have seen one case of rupture into the pulmonary artery when the symptoms consisted of sudden pain, collapse, want of pulse, and tumultu- ous action of the heart for about two hours before death. External rupture is comparatively rare. If such a rupture is impending, the fact will be recog- nized by the commencing lividity and finally gangren- ous appearance of the tensest portion of the projecting tumor. This accident is sometimes induced by straining or falling, or by rough handling. Physical Signs. — The foregoing symptoms (which are mainly those of excentric pressure) are indicative of intrathoracic tumor of some kind, but cannot indi- cate aneurysm specially. On observing any combina- tion of them, we must turn to the physical signs to determine the character of the tumor — they are, of the two, therefore, the more important; and both together will, in the majority of cases, enable the phy- sician to arrive at a positive diagnosis. These phys- ical signs are derived both directly from the tumor itself and indirectly from an examination of the neigh- boring organs which may have been pressed upon, displaced, or otherwise interfered with by the encroach- ing tumor. The signs, as regards the aneurysm, will evidently depend mainly upon its size and its exact position, especially as regards the surface of the chest . Inspection will readily demonstrate the existence of any distinct bulging of the parietes of the chest. This may be only a slight or ill-defined elevation of a cir- cumscribed area, or it may be a tumor of some mag- nitude. The elevated part, moreover, is seen to pul- sate (almost) synchronously with the apex of the heart. The situation of the pulsating prominence depends upon the portion of the aorta involved, and the direction in which it has been tending. Aneurysms of the ascending arch are most commonly seen in the second or third interspace of the right side. Those of the descending aorta will most commonly' reach the surface on the posterior or lateral wall of the chest. 413 Aneurysm, Internal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The skin over the prominence is usually healthy, epf when the external tumor is large, when it may be red or livid. There may be no elevation from the general surface, the eye detecting only a pulsating spot similar to that over the cardiac apex. In the absence of these more characteristic appearances, if the front of the chest be carefully examined, while the patient stands sideways to the observer, a more or less distinct systolic heaving of the chest wall can be noticed, especially when the respiration is withheld. This indicates usually an aneurysm of considerable size and deeply seated. If the heart be displaced, this fact can also be determined by the altered posi- tion of the apex beat. Palpation of the chest is of service only when the tumor sufficiently approaches the chest walls. Local fulness or bulging can be appreciated, pulsation can be located, and the force of the impulse measured. Fremissement, or thrill, systolic in rhythm, can also not infrequently be felt, perhaps over the entire area covering the tumor; and following this, sometimes a diastolic shock may be recognized. In obscure cases, in which a deep-seated aneurysm may be suspected, the bimanual method of examination may prove of great service. The patient's chest is firmly grasped between the two extended hands laid flat upon the surface. By this means a diffused sense of expansion will be experienced which is extremely significant and can be ascertained only in this way. The supra- sternal notch should also be explored. The patient's head being bent forward to relax the sternomastoid muscles, one or two fingers are pressed deeply into the fossa and beneath the manubrium sterni, when pulsation or thrill communicated from the transverse portion of the arch can be distinctly perceived. Another physical sign of very great diagnostic impor- tance, and one which is also to be obtained by the edu- cated sense of touch, is what is now known under the term "tracheal tugging," or Oliver's sign. To examine for this sign proceed as follows: Let the patient be seated upright and with the head well thrown back, in order to put the windpipe upon the stretch. Then with the finger and thumb of the right hand grasp the cricoid cartilage or the lower border of the thyroid, and make steady pressure upward. If a deep-seated aneurysm be present which impinges at all upon the trachea or one of its principal divisions, then a very distinct and unmistakable tugging downward will be felt with each systole of the heart. When the heart is acting strongly, or when aortic incompetence is present, considerable rhyth- mical pulsation may be communicated to the fingers from the adjacent carotids, but with a little care this cannot be mistaken for the tugging directly downward above described. I have observed a considerable number of cases of thoracic aneurysm, cardiac and other thoracic diseases with reference to this sign, and I have never observed it produced by any other con- dition but aneurysm. In one case, which I saw in consultation, there seemed clear evidence of an aneurysm of the transverse arch, and the presence of stridor and paroxysmal dyspnea showed its interfer- ence with the trachea and nerves. No tugging could be felt. The autopsy, however, showed that the tumor was completely filled with firm laminated fibrin, and its pulsatile character was lost. Except in cases of this kind (which must be of pretty long standing) tracheal tugging may always be looked for in central aneurysms of the chest. This sign was attributed by MacDonnell to pulsation transmitted downward to the left bronchus. It may, however, be present in any instance in which the aneurysm is adherent to the trachea, and Fraenkel has seen it in an aneurysm of tile ascending aorta in which firm adhesions were present between it and the trachea. A few cases are recorded in which a tumor lying between the aorta and bronchus lias given rise to this sign. Care must ]>r taken to distinguish a slight downward pulsation, often felt in healthy necks, from true tugging. Hall has described a diastolic shock following the systolic tracheal tug. Percussion elicits a flat note over the area through- out which the aneurysm is in contact with the chest wall. This area, of course, may give no idea of the actual size of the aneurysm, for its principal bulk may be buried beneath healthy lung tissue. A modified dulness may sometimes be found for some distance around the flat region. It is often impossible to separate the dulness of the aneurysm from that o solid organs, the heart, liver, etc". Of course, if the tumor be entirely deep-seated, the percussion may be everywhere normal. If also the lungs be emphyse- matous, no information can be obtained from percussion. Auscultation over an aneurysm of the aorta reveals of necessity only a systolic and a diastolic sound, such as we hear over the vessel itself. The systolic sound, however, may be modified, and is sometimes accom- panied by murmur. The modification consists gen- erally in loudness, while, at the same time, a sense of impulse is conveyed, the so-called bruit de choc. The diastolic sound is communicated from the aortic valves, any increase in their tension intensifying the second sound over the aneurysm. It is always accen- tuated when the diastolic shock is perceptible on pal- pation. Systolic murmurs are of tolerably frequen occurrence. They are probably produced in one of two ways: either by sudden alteration in the caliber uf the vessel (causing fluid waves or eddies) or by the vibrations produced by contained coagula or irregu- larities in the course of the blood current. The systolic murmur of an aneurysm is generally blowing in character, but sometimes possesses a de- cided musical or " cooing" quality. Its seat of maxi- mum intensity is likely to be the central part of the tumor, and it is not generally diffused to any very con- siderable distance from this. The significance of the murmur is derived from its seat of maximum intensity being away from that usually associated wit h valvular lesions, and from its being accompanied by a mag- nified second sound. Heard alone (i.e. without accentuation of the second sound) a systolic murmur is rather indicative of some other condition than aneurysm. Indeed, diastolic accentuation, if con- fined to some circumscribed dull area in the neighbor- hood of the aorta, is of more value than any murmur. Any murmurs generated at the aortic valves and orifice are likely to be transmitted through an aneu- rysmal tumor as well. Often, therefore, double aortic murmurs are to be heard in this situation. Sometimes, however, similar to-and-fro sounds are generated within the sac itself, their origin being declared by their being much louder over the corre- I sponding area than elsewhere, by being much more restricted to this region, and by not being at all neces- sarily associated with dilated hypertrophy of the left ventricle. A diastolic murmur alone may, exception- ally, be heard arising from an aneurysm, and Gerhardt states that a diastolic murmur may sometimes be heard in the left supraspinous area. Over the tumor the respiratory murmur is absent, but on passing just beyond the edges of this, the breathing sounds are heard, but generally of a somewhat bronchial character. In the same areas the voice will have a bronchial resonance, although decided bronchophony will not be found (or, at any rate, is rare). The pulse in internal aneurysm may, or may not, afford positive information. The arteries themselves are frequently in a diseased condition, fibroid or sclerotic, and may thus affect the pulse. The slate of the heart will also have to be taken into account. If, however, the blood be flowing into an aneurysm of considerable size, special alterations in the blond current in the parts on the distal side of this may ho observed and delineated. The effect of the diverticu- lum is to act like the empty rubber ball in the ordinary •II I REFERENCE HANDBOOK OF THE MEDICAL SI II A Aneurysm, Intern. tl syringe, i.e. to make the current more e eady anil l |J " spasmodic and jerky. When, therefore, :i gphygmographic tracing is taken, the curve is found ffer from the normal our in accordance with this hanism. The ascent of the systole is less abrupt, more gradual, and the descent also occurs without the game sharpness. The necessary result of this i< to render the apex of the cur\ e more rounded, less acute than that of the natural pulse. The larger the sac ami the more distensible the walls, the better this kind of tracing i- brought out, while fibrillation of the contents and stiffening of the walls tend to obscure these peculiarities and cause the tracing to resemble the normal curve. The value of the bservations is greatest when we examine at the same time the esponding artery of the opposite side, or else the same artery m- a branch of it i above the region of the suspected aneurysm. It is not uncommon to fuel such a degree of difference between the pulses of the two sides a< may lie clearly recognized by the finger. The differences consist in delay of the pulse and in alteration in its volume. Delay of the pulse in the radial artery is a diagnostic sign upon which too much stress must not be laid, and, indeed it is very often absent, or difficult to appreciate with the finger. Findley. however, has shown that it may be often detected by the clinical polygraph, and he regi the sign as due to the blood wave passing through ah aneurysm, and consequently of some value in local- izing the site of the aneurysm. Diminution in the «r of the radial pulse of one side is important as an additional point of evidence in a case of suspected thoracic aneurysm. Its positive value is, however, detracted from by a consideration of the fact that the same thing is often seen from congenital peeuliaritv or from irregular distribution of the blood-vessels of that arm. The latter possibility should always be sought for, and a comparison made between the bra- chials of the two arms. The alteration in the volume of the pulse may be produced by twisting or distortion of the vessel, by dragging upon it by the advancing growth, or by partial or complete obliteration of the lumen by the entrance into it of detached fragments of fibrin. The only special distinguishing mark of embolism is the suddenness with which it is apt to occur. Thoracic aneurysm is very frequently associated with changes in the heart and in the circulation. Other neighboring organs also become physically altered by reason of the pressure, or other interference, to which they may have been subjected. These con- ditions can generally be recognized by physical exami- nation. Enlargement of the heart does not arise from aneurysm, but often occurs from the associated arteriosclerosis, or from valvular defects, particularly aortic incompetence. Displacement of the heart is often seen. This is generally a downward displace- ment only, or with some inclination to the left. When the tumor affects the descending aorta, the heart is displaced forward. If incompetence of the aortic •s be present, as often occurs, its existence is iinized by the usual physical signs. The cause of the incompetence may be either atheroma, as above mentioned, or the altered caliber of the root of the aorta produced by the tumor, i.e. relative incompetence with healthy valves near to which the expansion has begun. Tumors near the origin of the aorta are also liable to cause pericarditis. This occurrence has frequently been found postmortem, and is occa- illy witnessed during life. Byrom Bramwell (" Diseases of the Heart and Thoracic Aorta." p. 71 1 1 says: "In any case of non-rheumatic pericarditis occurring after the age of forty, in which the cause of the pericarditis is obscure, I strongly suspect the pres- ence of an aneurysm." The same author suggests that aneurysm in the same locality may account for certain eases in which pericarditis and angina pectoris have been observed at the same time. Pleurisy is a common complication, and musl be looked for either from friction sounds or from the signs of liquid effusion, curs st often with aneurysm of the descending aorta. The existence of a pleurisy at the base of one lung, followed by prolonged pain iii the region, otherwise ted for, will certainly sometimes lead us aright by suggesting aneurysm. If a main bronchus be compressed, the correspond- ing lung becomes comparatively airless, it- circuls is impaired, and catarrhal conditions prevail. In consequence of this the following physical signs will be found, viz., moderate dulness on percussion and enfeebled respiration, with or without moist i In a few of these cases a whistling sound can be made out over the situation of the I 'I tube. Changes in the lungs are not uncommon in aneu- rysm. Owing to the frequency with which the left hus is compressed these changes are much n frequent in the left than in the right lung. Fibroid changes with retraction, gangrene, and suppuration are seen and may even mask the primary disease. i onstriction of the left bronchus by aneurysmal pres- sure sometimes sets up bronchiectatic dilatation below the site of stricture. Such a condition is usually not recognized during life, but exception- ally symptoms and signs of bronchiectasis can be discovered. We may now consider more particularly the chief symptoms and physical signs which indicate an- eurysm in the different parts of the thoracic aorta. eurysms of the Hoot of the A< a (the Sim Valsalva). — Those aneurysms which spring from the very commencement of the aortic tube are not very uncommon. They are frequently entirely latent, but symptoms of pericarditis, or of angina pectoris, may occur. They are quite liable to cause aortic incom- petence. Such tumors are very dangerous, as, before arriving at any great size, they are liable to rupture, especially into the pericardium. Bramwell figures (op. cit.. p. 720) a remarkable aneurysm springing from this situation: it attained an enormous size, perforated the sternum, formed a large external pro- jection, and finally ruptured through the integument. Aneurysms of the Ascending Portion of the Arch. — In this region of the tube, dilatations, cylindrical or spindle-shaped, are most frequent, but saccular aneurysms also occur. The latter are then generally situated upon the right side of the aorta. In an early stage of dilatation we shall find altered pitch of the percussion note to the right of the sternal margin above the second rib, and the pulsation of the aorta becomes stronger and more perceptible above the sternum. As it increases, we get more decided dulness extending to the right above the second rib. The first sound becomes dull and the second more forcible and clanging. A systolic murmur may then become developed in the same area, and this, by its seat of origin and want of diffusion, may be distinguished from a valvular murmur. Disease of the aortic valve frequently coexists. Aneurysm in the ascending arch has a tendency to reach the surface of the chest, and can therefore generally be made out with ease by the physical signs. The locality where pulsation and bulging are most apt to be discovered is the neighbor- hood of the second costal cartilage of the right side. The edge of the sternum and one or two ribs become eroded, and the tumor, which may be of considerable size, projects. The pulse in the vessels on the right side will be small and delayed compared to that in the Is on the left, if the innominate be involved. Compression of the superior cava or right innominate vein may happen, with resulting dilatation of the veins of the upper half of the body or right arm. The symptoms commonly complained of are pain and dyspnea, perhaps cough. When the aneurysm is of considerable size, numbness and weakness in the right arm may occur from pressure on the brachial plexus. The right bronchus may also be sometimes 415 Aneurysm, Internal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES compressed. Rupture of an aneurysm in this situa- tion occurs most frequently into the right pleural sac, the pericardium, the lungs, or externally. In one of my own cases, already mentioned, rupture took place into the pulmonary artery. Aneurysms of the Transverse Portion of the Arch. — These may be either spindle-shaped or, more com- monly, saccular. As they occupy that portion of the arch of the aorta from which spring the great brachial and cephalic branches, the latter are quite frequently involved in the aneurysmal growth. They are com- mon, but somewhat less so than those of the ascending portion. Their situation is such that they, soon after attaining any size, necessarily impinge upon some of the important structures in the center of the thorax, giving rise in consequence to decided evidences of intrathoracic pressure. The presence of a pulsating tumor in this region will also cause easily recognized changes in the percussion of the sternum and its mar- gins, and can further be detected by the sense of touch behind the manubrium. Aneurysm in the transverse arch is therefore, as a rule, readily diag- nosed except when the tumor is quite small. Some- times, even before any other signs have developed, the aneurysm may be discovered by means of the finger pressed well down behind the sternum in the jugular fossa. As the expansion of the aorta here increases it pushes aside the edges of the lungs, and dulness becomes well marked over the first piece of the ster- num, and to a variable distance on either side of this. Then a heaving prominence makes its appearance in the same region, and, following upon the absorption of the sternum and upper ribs, an external tumor becomes developed which may even reach a large size. The radial pulses of the two sides quite fre- quently differ in size and fail to beat with the usual synchronism. This sign is more often met with in an- eurysms of the arch, because here the innominate and subclavian arteries are so apt to have their caliber interfered with by pressure, by twisting or dilatation, or by the entrance of eoagula. The parts most liable to compression in these cases are the esophagus, trachea, recurrent laryngeal nerve, and left innominate vein. If the concave border of the arch be also involved, the left bronchus is liable to be partially or wholly obliterated. The signs by which these various con- ditions can be recognized have been already considered. Rupture occurs into the trachea, the esophagus, or the pleural cavity, or more rarely into the mediastinum, the pulmonary artery, or one of the large veins. Aneurysms of the innominate artery alone are rare, but we oftener see tumors of the arch associated with more or less considerable dilatation of the innominate trunk. The enlargement will be found beneath the right sternoclavicular articulation and inner part of the first rib, and it may extend into the neck beneath the sternomastoid muscle. In these situations we must look for the usual local signs, swelling, pulsation, and bruit. The latter may be heard up the carotid. The effect upon the distal arteries is generally well marked. The symptoms are chiefly pain, both local and more especially radiating up the right side of the neck and back of the head, sometimes down the right arm, with numbness; and if the tumor be larger, there will be signs of compression of the trachea or the esophagus or an innominate vein. Cases sometimes arise in which it is extremely difficult to determine whether the disease is confined to the innominate artery or occupies as well a portion of the arch at the origin of this vessel. For instance, a man came under observation a short time ago at the Montreal General Hospital, with a strongly pulsating tumor rising out of the neck above the right sternoclavicular articula- tion. Fenwick, whose patient he was, believed it to be purely innominate. Its strict limitation to the area near tiiis vessel, the distinctness with which the cylindrical tumor could be defined by the examining finger, t he interference with the pulsations in the radials, and the absence of all signs of swelling of the arch, as determined by most careful examination, all seemed to favor this conclusion. This opinion was confirmed at a consultation of several members of the staff, and it was decided to recommend treatment by distal ligature. This the patient refused to submit to and was discharged. He subsequently died suddenly', while running, from rupture into the pericardium of a small aortic dilatation just above the valves. The aneurysm in question was found at the autopsy to be entirely aortic. A remarkably elongated saccular dilatation sprang from the arch directly behind the innominate artery (somewhat compressing it) and appeared above the inner edge of the clavicle. The innominate was completely pervious and of normal size. The deception was complete and would have given rise to a grave error of treatment had the patient consented. Although, as in the ease just related, mistakes of this kind are sometimes quite unavoidable, yet, in the majority of cases, a thorough investigation of all the symptoms and physical signs will suffice to make a diagnosis. Aneurysms of flic descending thoracic aorta are less common than the others. They also may be cylin- drical or saccular. From the depth at which they are situated in the chest, and from the thickness of the structures everywhere surrounding them, they are difficult of detection, and as the symptoms from them may be only slight and ill defined, they may con- tinue for a long time unsuspected. Pain is, however, seldom absent, and when due to pressure on the nerve roots is of an extremely violent and intractable character. It may be accompanied by hyperesthesia or anesthesia of the skin, and MacDonnell has re- corded an instance in which there was sweating in the course of the nerves. This point has been already sufficiently dwelt upon. The earliest physical signs consist in localized dulness and pulsation to the left of the spine, and enfeebled breathing over the same area. Later on, a systolic bruit may be heard. ( )ccasionally, retardation of the left femoral pulse, as compared with that of the radial, has been observed. When of large size, the aneurysm pushes the heart forward, and the heaving impulse of the tumor can be felt anteriorly through the heart. A rare symptom is dilatation of the veins on the anterior aspect of the chest from pressure upon the azygos and intercostal veins. Lying against the vertebral bodies, these aneurysms very commonly produce erosion of those structures; and if this be sufficiently considerable, bending of the vertebral column occurs, with posterior curvature. From this cause, or from opening of the vertebral canal, pressure is sometimes brought to bear upon the spinal cord itself, with a resulting paraplegia. The esophagus is sometimes compressed and dysphagia produced. Attacks of pleuritis in the lower part of the left side are a very frequent accompaniment. These usually result in plastic effusion, but, at times, even pretty considerable quantities of serum may be found. Some years ago I found a hospital patient com- plaining of stitching pain in the left side. Aery moderate effusion was determined by physical ex- amination. There had been slight pain in the back for some time previously, but this had not been of sufficient duration or intensity to lay stress upon. The fluid continued to collect, and was removed by as- piration, with relief. A few days afterward he died suddenly from rupture of an aneurysm of the descend- ing aorta into the same pleural cavity. Wynter records cases of simulating aneurysm of the descending arch associated with a ringing second sound, tracheal tugging, paralysis of the left recurrent, nerve, and downward displacement of the heart owing to lengthening of the aorta. He believes these signs are due to atheroma of the upper portion of the arch and that they can be distinguished from aneurysms of the arch only by x-ray examination. Rupture of these aneurysms occurs most frequently 416 REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Aneurysm, Interna] Into the left pleural cavity, sometimes into the right, and occasionally into the esophagus. Cases are known in which the sac opened into the spinal canal. Diagnosis. The recognition of thoracic aneurysm i t as easy in some cases as it is difficult in ol hers. During the i >:i-t decade ii has become more generally recognized that a not inconsiderable number of cases of trysm arc entirely latent. An important method in the recognition of such eases has been made by the application of the x-rays. Cases otherwise obscure ran be cleared up in this way, and when aneurysm is falsely suspected an x-ray examination may disprove its existence. Observations are' best carried out by means of the fluorescent screen, when a distinct en- largement lying in the course of the aorta is detected. Pulsation is sometimes observed, and, its occurence ngthens the view that an aneurysmal tumor is ent. Williams states that the movements of the diaphragm are often less on the left side, due prob- to pressure on the left bronchus. Care must .crcised not to mistake enlarged glands or other intrathoracic tumor for aneurysm. Such an error is likely to occur only when the growth lies in contact with the aorta. By this method of examination the diagnosis often becomes apparent in obscure cases, and aneurysms are limes found which are unrecognizable by other methods of physical examination. Superficial, strongly pulsating aneurysms are readily observed, and not unfrequntly the throbbing will have been noticed by the patient himself. On the contrary, deep-seated dilatations may give no appreciable physical signs, and in that case the diagnosis may be obscure. Furthermore, if, in one of these obscure cases, the aneurysm causes no symptoms by its pressure, then the diagnosis becomes impossible. Not a few aneurysms of the ascending arch, even of considerable size, prove the cause of sudden death in persons previously believed to have been in good health. These, having caused no symptoms, had never been looked for, but could undoubtedly have been detected by physical examination. The combination which gives the greatest certainty to the diagnosis of thoracic aneurysm is the union of physical signs of tumor with pulsation in the course of the aortic arch, together with some, or best, several, of the pressure symptoms enumerated. The difficulties in the diagnosis of these cases arise from the great variability which is met with in the manner in which these different in- dications may be grouped together. Thus we meet with cases in which some of the physical signs of aneurysm are observed, and no pressure symptoms; others, again, in which there are evident pressure symptoms, with perhaps only a few of the signs of aneurysm. In not a small number of cases the con- ditions lead to the recognition of an intrathoracic tumor, and the difficulty begins only when we endeavor to differentiate between a solid tumor and aneurysm. The resemblance between an an- eurysm and a solid tumor placed between the chest walU and the aorta maybe very close. In both there may be dulness on percussion, pulsation, and a recognizable bruit, and pressure symptoms of identical character may also be present. The chief points of distinction ari' the following: In the case of the neo- plasm, the dulness is likely to be less clearly restricted to the aortic region, the pulsation will not be at all so forcible, and the systolic bruit will probably not be followed by an accent uated second sound. Bronchial respiration is commonly heard over a solid tumor, while enfeeblement or silence is the rule in aneurysm. Again, persons with aneurysm are not likely to suffer severely in their general nutrition and appearance, while the contrary holds good with reference to nearly all forms of intrathoracic solid growth. Attention to the following points may also assist the investigator in doubtful eases. Aneurysm is many times more frequent than solid tumor. It occurs much more often in men than in women. It i- favored by a in t.iry of syphilis, rheumatism, or -train. Pulsating empyema is i lition, which some- times simulates aneurysm. The chief physical signs to be here met with will be dulness 1,11 percussion and local pul ation, but no pic -lire symptoms will be present. Examined closely, the dulness will be ob- served to be less clearly localized in the aortic region than is that of an aneurysm. Moreover, other sign of arterial disease will be- wanting, and. on I he other hand, there will be some evidences of disease in the pleura or the lung, accompanied by a certain degree of constitutional disturbance. These differences will usually suffice to prevent error. Puncture with a tine aspirator needle will, in any case, clear up the diagnosis. Violent throbbing pulsation of the aorta in eases of severe aortic regurgitation often leads to a sus- picion, or even to an erroneous diagnosis, of aneurysm. The pulsation, however, ha- not the heaving charac- ter of aneurysm, and there is an absence of pressure J nipt ollis. Prognosis. — It is usually a matter of considerable difficulty to form a satisfactory opinion as to the prospects of life of a person suffering from thoracic aneurysm. Undoubtedly the disease generally tends to prove fatal, and is actually the immediate en of death in the majority of eases; and yet, in a certain number, increase in the tumor is arrested and moder- ate health is enjoyed for perhaps a period of several years, even (hen the fatal event being brought about by some affection entirely independent of the aneu- rysm itself. It is often clearly impossible to estimate at all accurately the size of a deep-seated tumor, or the degree to which it may lie against important adjacent organs; and hence ruptures in various directions, which no skill could possibly foresee. Those aneurysms which arise from the root of the aorta are the most dangerous, as they tend most frequently to rupture while yet small. Those of the ascending arch — if they grow forward and to the right — are calculated to permit of the longest tenure of life. Those of the transverse arch and descending thoracic aorta are probably, on the whole, more favorable than the first and less so than the last; the reason for this, of course, being their greater proximity to numerous important structures, which can hardly escape from injurious pressure. Our opinion, therefore, of the probability of the pro- longation of the patient's life must depend upon the situation of the aneurysm, the fluidity or the contrary of its contents, and the presence or absence of symp- toms of compression, to a serious extent, of the sur- rounding parts. If this be well marked upon the trachea or esophagus, a fatal result may lie anticipated before many weeks or months. Other conditions to be considered are the following: Mode of life; if a person with aneurysm is obliged to earn his living, and especially if the occupation followed is at all laborious, his chances of living will be far less than those of his more favored fellow who is able to live at ease and free from care. Rest is so important in these eases that if this cannot be secured the disease is almost sure to be progressive, and perhaps even to advance rapidly, while, on the other hand, it seems sometimes surprising how long the fatal end can be averted, even in advanced cases, by the observance of great precautions in this respect. This remark will also necessarily apply to the cases of patients who, from irritability of temper or other similar causes, refuse to carry out this essential principle of their treatment. The temperament of the patient is of importance, for anger, excitement, and, indeed, any violent reaction may be followed by the most serious results. Indulgence in alcoholic liquors is sure to interfere with the quiet action of the heart which is so desirable; intemperance must, therefore, influence strongly our prognosis. Vol. I. — 27 417 Aneurysm, Internal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Associated Conditions. — In estimating what is likely to be the future of any given case of thoracic aneurysm, it is important to study carefully any pathological conditions which may be associated with it— such, for example, as affections (especially valvular) of the heart, of the lungs, of the larynx, of the bronchi, etc. — and to assign to each its true value as a factor in the problem. Finally, the general condition with reference to nutrition, muscular development, etc., must also take its place in rendering the prognosis either more or less favorable. Treatment. — Aneurysm within the chest is capable of the same spontaneous cure which occurs occasion- ally elsewhere. Complete coagulation and hardening of the contents, with arrest of all symptoms, is, how- ever, extremely rare. Still it is always obviously a duty to endeavor to place a patient who is the subject of this formidable disease in as favorable a position as possible for this process to occur. All treatment, therefore, which is not merely palliative should be directed toward insuring conditions likely to promote firm coagulation within the sac. In the large majority of cases of intrathoracic aneurysm we are, from the nature of things, pre- cluded from those methods of treatment which are applied directly to the tumor itself or its immediate neighborhood, and are frequently distinctly curative. We are, on the contrary, compelled to treat these cases by general measures and by such indirect means — drugs — as experience has proved to be of value. The objects in view may be briefly stated to be to reduce the tension within the aneurysm, to secure regularity of the heart's action without fre- quency, to maintain the blood in good chemical con- dition without undue bulk, and to favor thickening of the sac's walls. To follow out these indications it is necessary to secure the full direction of the case for, perhaps, several months. If the physician, therefore, is to meet with any success, it is absolutely requisite that he should have the hearty cooperation of the patient, who, if sufficiently intelligent, must be made acquainted with the nature of the case and the urgent need of his assistance, irksome though he may find it to be. The recumbent position, for a length of time, is always to be recommended. The effects of this measure alone, are often sufficiently striking. When the person's circumstances permit, the restriction to a lying posture should be absolute, and should be persisted in for several months, unless the general health appear to be suffering materially from the close confinement, when, with due precautions, sitting up and slow walking may be permitted. If, on the other hand, circumstances prevent absolute rest from being carried out, then, at any rate, very stringent rules must be insisted upon, governing the patient's entire mode of life, with the view of insuring the least possible muscular exertion. This is a point on which too much stress cannot be laid. These patients live constantly on the edge of a precipice, yet, when immediate suffering is relieved, this fact is too often lost sight of, with disastrous results. A patient whom I treated during a year not long ago, for an aneurysm of the ascending arch, was so far benefited that he took a situation as a messenger. In spite of all warnings to the contrary, he soon undertook to handle heavy baskets and other pack- ages. One day, shortly after, he experienced sudden pain in the chest, followed by the extraordinarily rapid development of an external tumor. This quickly attained the size of a child's head, and proved fatal, with great suffering. Hardly less important than physical rest is mental quietude. Habitual worries of all kinds should be as much as possible excluded, while actual excitement is in every respect highly dangerous. A fit of anger or other violent emotion may prove fatal, either by actually causing rupture of the sac or (as in a recent case of my own) from syncope. The diet is a matter of importance. A very old treatment of aortic aneurysm is that of Valsalva, in which repeated blood-lettings were practised, . to- gether with a gradual restriction of the food until the amount of this was brought within the lowest possible limits short of actual starvation. The fallacy of this proceeding has, however, been long ago demonstrated. Blood-letting has but little, or but a temporary, effect upon the blood pressure; and the withdrawal of food causes anemia and weak- ness, with irritability of the heart and impaired nutrition of the arterial walls, which conditions indirectly aggravate the disorder. The result of experience shows that the formation of a coagulum which is likely to be of service in the process, will proceed better if the patient be not too much reduced, Tufnell, of Dublin, is the only comparatively recent writer who has advocated the starvation plan. Conformably with his recommendation, the system has been extensively tried, but few are found who can report results calculated to lend support to its efficacy. The quantity of fluid allowed should not exceed forty or fifty ounces daily; it is difficult to get patients to submit to smaller quantities for a prolonged period of time. If the patient be plethoric and show evidences of congestive tendencies, then our treatment may well be begun by the adoption of depletory measures for a time — a low diet with laxa- tives or saline purgatives. As regards medicines, many have been tried, but few have proved useful. The most valuable drug is undoubtedly iodide of potassium. The good effects of the iodide were described by Chuckerbutty in 1862, and by Roberts in 1S63, and they were em- phasized and enlarged upon by George Balfour a few years later. Since that time it has been exten- sively employed, and has«ontinued to grow in favor. The two former writers considered that it acted by inducing increased coagulability of the blood, but this view is not shared by Balfour. He considers that the iodide has "a peculiar action on the fibrous tissue, whereby the walls of the sac are thickened and contracted, while if coagulation should take place within the sac, it plays but a very secondary and unim- portant part, depending for its occurrence solely on the remora of the blood, and is in no respect due to the iodide of potassium." This corresponds entirely with the results of my own observations, for in one case, in which the relief to pain and the general improvement had been very marked for a long time under this treatment, the autopsy subsequently showed that not a particle of fibrin had been deposited on the walls of the sac. The symptoms which specially indicate the use of the drug are pain and troublesome cough. The special pains of thoracic aneurysm are generally very rapidly alla3*ed, and are often for a great length of time held in abeyance by this agent; and the same may be stated with reference to tin? troublesome attacks of irritating cough which the tumor may excite from time to time. Independently, however, of its employment for the relief of these urgent symp- toms, it is to be administered steadily for such a I as may be thought necessary to influence, as al" the disease itself. The dose usually given varies from gr. x. to gr. xxx. thrice daily. Balfour, who formerly inclined to the larger dose, thinks now that fully as good effects can be obtained from smaller ones. His rule is to employ such a quantity as will lower the blood pressure without increasing the frequency of the cardiac contractions. Beginning with ten-grain doses, ascertain the pulse rate (the patient h< recumbent), and increase to fifteen; if no increase in the pulse be observed, this is to be continued; but if the pulse gets quicker,- then return to ten. It is rare that more than fifteen grains can be borne within the limits of this test. The treatment must be persevered 4 IS REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aneurysm, Internal in, mi the least, for several months, and, to give it a f:iir trial, probably for a whole year, or even longer. If troublesome erupt inns are produced by the potash, an intermission must be allowed till these are recovered from. II is also well to remember that some persons who are thoroughly intolerant of iodide of potassium , J,, takciodide of odium without any outward effects. Balfour speaks truly when he says the results (from iodide treatment) "are extremely encouraging; and when we reflect upon the entire absence of any risk to tlic patient from the treatment, and the almost certainty of relief to his sufferings and prolongation of his life being at least attained, I think I am warranted in saying that no treatment for internal aneurysm hitherto devised holds out anything like an equal prospect of relief, if not of cure, with that by the i if potassium." Tlic hypodermic injection of a one-per-cent. solu- tion of gelatin in normal saline solution has been gly recommended by Lancereaux, with the view of causing coagulation in the sue. From 50 to 100 o.c. may be injected beneath the skin of the buttock, or thrown deeply into the muscles. There is some- times considerable local pain and even general febrile reaction after this procedure. Although successful have been reported, the method is by no means free from danger. Serious and even fatal results have followed the injections, owing to the detach- ment of large emboli. This method has not stood the of experience and is now seldom used. Christopher Heath and a few others have sug- gested and practised ligature of one or more of the great branches of the aortic arch, the object, of course, being to retard still further the blood current and thus promote coagulation. Some support is given to this procedure from the benefit that has been observed in certain cases of aortic aneurysm in which the carotid and subclavian of the right side had been ligatured, under the impression that the disease was confined to the innominate artery. At most it would be applicable only to cases in which the tumor was sacculated and either involved the root or was situ- ated close to the origin of some of the great vessels. Evidence of extensive atheromatous disease would preclude any prospect of advantage from this sur- gical procedure. The method of all others which seems to hold out the greatest prospect of success, when it is decided to penetrate the sac, is that first suggested by Moore, and subsequently modified by Corradi. It consists in the introduction of ten or more feet of coiled gold or silver wire into the sac through a hollow needle, insulated by being coated with French lacquer, com- bined with the passage of a galvanic current of fifty to seventy-five milliamperes, the anode being con- nected with the wire. It is applicable only in cases of sacculated aneurysms. In the thorax the .r-ray is an indispensable aid, especially the fluoroscope, in revealing the pulsating sac; a local anesthetic is used to introduce the needle through the skin. In one case Finnic removed the greater portion of the sternum and three adjacent ribs to gain better access to the sac. In abdominal aneurysm an incision is required through the abdominal wall in order to apply this method of treatment. The current should pass for at least an hour and Finnie in his later cases has continued it for two hours. In favorable cases decided relief to pain has been obtained with lessening of pulsation; and in a considerable number of reported cases marked improvement has been noted. From the nature of the disease cure can seldom be expected, and has been reported in but few instances. Certain risks must be faced in undertaking an opera- tion of this character. Embolism has occurred and also rupture of a subsidiary sac. Sloughing in the course of the wire or in the sac itself, with subsequent hemorrhage has also been observed. Although the special treatment of aneurj m in the majority of cases con i I of prolonged rest and the administration of iodide of potassium, a al detailed, (here are be ide the e certain therapeutic measures al our command for the relief of individual symptoms. Excited cardiac action and palpitation are be I relieved by the judicious use of morphine and the employment of a bladder of ice over the front oi the che t. The pain, it has been already stated, is generally best treated by the iodide of potassium. If, how it be very severe, ii may be necessary to use hypo- dermic injections of morphine until the iodide shall have had time to act. Moreover, we do meet with ran' cases in which the effect of the iodide ultimately bee s lost, and our only resort is the frequent use of morphine to make life bearable. ( Ine very marked ease of this kind came under my notice in the person of a hospital patient. His aneurysm was as large as a cricket ball, and almost as solid. Neuralgic pains were complained of persistently, were relieved for a considerable time by the iodide treatment, but, for more than a year previous to his death, we were obliged to administer daily hypodermics of mor- phine in considerable quantity. Pain of well-defined neuralgic character (especially along the intercostal nerve) is decidedly benefited by the application of small blisters over the most tender parts. Dyspnea, if due to accompanying catarrh, must be treated with reference to the latter disorder. But if, as is most frequently the case, it is the result of mechanical pressure and irritation of nerves, recourse must be had to sedatives and narcotics, especially morphine and hydrocyanic acid. Alcohol in toler- ably full doses is also of considerable assistance. If a projecting tumor form, care must lie taken to protect it from injury or friction by some arrangement of pads or a shield of some smooth metallic substance lined with cloth. When rupture has actually taken place, we can probably do nothing; but if any preliminary bleeding should occur, we may endeavor to prevent this going on to rapid hemorrhage by the use of ice externally and the administration of astringents, while the most perfect quietude is enjoined. Abdominal Aneurysm. — Symptomatology. — Aneu- rysm of the abdominal aorta is occasionally latent, as in two of Osier's series of eighteen cases. In a few instances, again, aneurysmal tumors may reach a considerable size without the distressing symptoms which usually accompany the malady. The earliest, the most persistent, and the most distressing symptom is abdominal pain. As Beatty long ago pointed out, the pain has a double character, being constantly present as a dull aching sensation in the abdomen and back, and subject to paroxysms of extreme violence which even large doses of mor- phine may only partly allay. The site of pain in these crises is situated in the abdomen and back, and is due to pressure on the lumbar nerves. These paroxysms may also radiate more widely, down the thighs or to the testicles; they may simulate renal, hepatic, or intestinal colic and have even been mis- taken for the abdominal crises of tabes. The pain may be increased by the taking of food, as in Beatty's case; Hoyle records cases in which it was increased by the respiratory movements. Other symptoms are due to pressure on surround- ing structures. Vomiting is present in many in- stances, and pressure on the duodenum may induce partial obstruction with dilatation of the stomach, as in a case recorded by Osier. Dilatation of the esophagus from compression of its lower end has also been noted by the same observer. When the tumor is in the proximity of the bile ducts, jaundice may result and enlargement of the 419 Aneurysm, Internal REFERENCE HANDBOOK OF THE MEDICAL SCIENCES liver may follow pressure on the hepatic vein-;. Ascites is an extremely rare manifestation of aneu- rysm, and edema of the extremities and trunk is of little diagnostic import. Fever is usually absent and its presence denotes a complication. The nutri- tion of the patient often fails to some extent, but in some cases extreme emaciation is a noticeable feature and may be attributed to loss of rest, to gastric dis- turbance and possibly in some instances, as in Pepper's case, to occlusion of the thoracic duct. Aneurysms of the various visceral arteries are usually -mall in size and are seldom recognized during life or until fatal rupture lias occurred. They are frequently of mycotic origin, or follow an acute infection. They usually run an acute course and occur in younger individuals than the more common form of the disease. The branches of the celiac axis, the superior mesen- teric and renal arteries are the vessels most commonly involved. Dean and Falconer refer to fifty instances of aneu- rysm of the hepatic artery of which seventy-three per cent, followed acute infection. In their ca jaundice developed twenty days after pneumonia, and hematemesis and melena resulted from rupture into the dilated bile duct. In a case recorded by Schultz, aneurysm developed as a result of erosion of the outer coats of the vessel from gallstones. The superior mesenteric is more commonly affected than other vessels. Aneurysms of the renal artery are very unusual and sometimes lead to hematuria. In a case of Keen's an abdominal tumor was removed with the kidney and subsequent dissection proved the mass to be an aneurysm of the renal artery. By far the most common termination of abdominal aneurysm is rupture. In 233 cases collected by Nixon this occurred in 152 instances; of these there were sixty-five retroperitoneal, forty-five intraperitoneal, seven pleural, one esophageal, and four pulmonary. Melena and hematemesis indicate rupture into the intestines or stomach. Elbe has reported a case of rupture to the vena cava and states that there are only four recorded cases (Deutsche med. Woch., 1910). Rupture into the peritoneum is usually rapidly fatal; when retroperitoneal the termination is more gradual and the symptoms may be those of acute peritonits. Osier refers to four cases operated on for appendicitis. The recognition of aneurysm rests on the discovery of a pulsating expansile tumor. If large it is visible, conveying a distinct impulse to the abdominal wall. Careful inspection of the lumbar region in a good light sometimes reveals pulsation of an aneurysm not seen in front. Pulsation in the epigastrium or along the front of the normal aorta is frequently found, particularly in neurotic individuals, but in aneurysm it has an expansile character, pulsating not only from before back but from side to side and separating the observ- ers hands when laid on each side of the tumor. A thrill is occasionally felt. The consistence of the tumor varies with the amount of fibrin deposited in the sac. When the latter has thin walls it is soft and fluctuating and can sometimes be emptied by pres- sure. With a large deposit of fibrin the tumor has a more solid character and pulsation may even cease. When connected with the aorta aneurysms are commonly fixed, they do not alter with change of posture, and he behind the alimentary tract. In the case of large tumors these may however come for- ward and give rise to a dull note on percussion. The surface of t he tumor is smooth and only exceptionally lobulated. A bellows murmur is heard in a considerable number of cases and in suspected cases the stethoscope should be carefully used in the lumbar region as well as over the abdomen. Diagnosis. — With a history of severe and persist- ent abdominal pain aneurysm is one of the condi- tions which should be considered, and evidence of syphilis increases the probability of such a condi- tion being present. The difficulty of recognition is shown by Bryant's collection of fifty-four cases from Guy's Hospital, in which only one-third were recognized during life. l"n fortunately the .r-rays render little or no assistance in the diagnosis of abdominal aneurysm owing to the impermeable character of the abdominal viscera. Treatment. — See the section on Thoracic Aneurysm. Cerebral Aneurysms. — Miliary aneurysms, de- scribed by Carcot and Bouchard, are visible to naked eye and vary in size from two-tenths to one millimeter. They are most readily seen in the i volutions and occur in order of frequency in the optic thalami, pons, convolutions, corpora striata, cerebellum, medulla, middle peduncles, and centrum ovale. Their number is very variable, from two to three to as many as one hundred. They derive their importance from the fact that they are sometimes the source of cerebral hemorrhage, particularly in aged in- dividuals. They result from degenerative changes in the minute \ r essels and are frequently accompanied by atheroma of the larger cerebral arteries. Aneurysm of the larger arteries is a rare condition, occurring nineteen times in 9,000 autopsies collected from Guy's Hospital by Pitt, and seven times in 501 cases of aneurysm according to Crisp's figures. 'I seldom attain a size larger than a walnut and fre- quently lead to fatal rupture when no larger than a pea. The middle cerebrals and the basilar are more often affected than the other vessels, then the internal carotids. The other cerebral arteries, the vertebrals and the communicating arteries occasionally suf- fer. Beadles (Brain, Vol. xxx.) has collected cases and classifies them symptomatically in four groups: 1. Those in which rupture and apoplexy have been the first signs of cerebral disease. 2. Those in which fatal apoplexy has been preceded by symptoms suggesting cerebral tumor or other cerebral lesion. 3. Those in which there have been symptoms of cerebral tumor only. 4. Those discovered accidently after death or latent during life. In nearly half the cases (46.3 per cent.) apoplexy was the first symptom, and in only a little over a third of the cases | :;7.1 1 per cent.) were signs of tumor or brain lesion present, and even in these the symp- toms were by no means always distinctive of organic disease. In thin-walled sacs early rupture is apt to occur, and symptoms from pressure on the nerves at the base or on the cerebral substance are often absent. Where the sac has a thicker and harder wall pressure symp- toms appear more frequently. These cases may last for years and death often results from pressure on the medulla or other portions of the brain. In cases where the symptoms of tumor are pres- ent, headache, vomiting, recurring convulsions, and optic neuritis, sometimes with retinal hemorrhaj may occur. Owing to the contiguity of the vessels and cranial nerves, one or more of these may suffer from pressure. Symptoms due to pressure on the pons and medulla result most frequently from dis- ease of the basilar artery with which these structures are in close contact. A murmur, according to Beadles, is seldom hi and a diagnosis based upon it has has been proved ci hi oct in only two instances by postmortem examina- tion. This fact is not surprising when the small si/e and deep position of these aneurysms are remembered So many other conditions may produce a cranial murmur that no significance should be attached to this sign. In these cases however blood extravasation is usu- 420 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angina Abdominis ally in the tumor or brain substance, and is less likely to reach the surface. (I,,- diagnosis of cerebral aneurysm is seldom if over made with certainty. Wichern (2>< Ztitschrift fiir S < rv< nln ilkitttdr. Kill') puints out thai rigidity of the nock is frequently present with the apoplectic attacks, signifying a surface hemorrha in such instances lumbar puncture would reveal the presence of blood, and this combination of signs should suggest aneurysm as the probable source of hemor- ;e. The occurrence of apoplexy in an individual who has suffered from signs of tumor might also -t such an explanation, and the finding of bl 1 in a lumbar puncture would be further evidenci in its favor. On the other hand cerebral growths are occasionally attended by sudden apoplectic attack usually due to hemorrhage. In these cases howevei the extravasation is usually in the tumor or brain tance and blood is therefore not likely to be pres- ent in the spinal fluid. F. G. Finley. Angelica. — Angelica L. (fam. Umbelliferce) is a genus the limits and dimensions of which are greatly in dispute among botanists, the various sub-genera of one author being regarded as so many distinct genera by another. As recognized by Messrs. Engler and Prantl, whom we follow, it contains about twenty- live species, most of them natives of the cool tem- perate regions of the northern hemisphere. The plants abound in the aromatic principles of the family. A number of them have been employed in domestic practice, and two, under the names "Euro- pean'' and "American" angelica, have been very extensively used in medicine. pean Angelica is the rhizome and roots of lica archangelica L., a biennial, four to six feet high, with a stout, hollow, purple-green, fluted stem, large decompound leaves with clasping petioles, and large umbels of white flowers. It is a native of far Northern Europe and Asia, and is very extensively Cultivated, our commercial supplies coming mostly from cultivated plants of Germany and France. It is one of the few vegetables whose use began in the extreme north of Europe and extended south- ward. It was an article of food in Norway and Iceland many years ago, when its spicy taste made it a grateful addition to the monotonous diet of the North. Later, in the fifteenth and sixteenth centuries, it was generally cultivated throughout Central Europe. .Since then, the use of angelica has been gradually diminishing, milder-flavored vegetables taking its place, and it is only grown at present to fill a very moderate demand in domestic and veterinary medicine, confectionery, and liqueurs. It is important to note the extensive use of the "candied" stems (Angelica glare) as a confection. since important cases of poisoning sometimes result from the ignorant use of certain toxic plants which bear a close resemblance to this. The "root" consists of a large short rhizome, ter- minated above by a hollow stem, and often worm- eaten. Below, it divides into numerous thick, fleshy roots, four millimeters (one-eighth of an inch) in thickness, and twenty or thirty centimeters in length, of a blackish-brown color, much wrinkled longitudin- ally, and tubereulated. They are rather soft and pli- able, brownish-white within, and in the dried speci- mens He in a parallel tress or bunch. The odor is rather pleasant: the taste at first sweetish, later bitter and musky. Radially arranged oil-ducts and resin cells are to be seen under the microscope on section, chiefly in the cortical portion. The constituents of angelica are, first, an essential <~>il, containing phellandrene, and probably pinene and evmene, of which it yields from eight-tenths to one per cent.; this has the odor of the plant and the usual carminative qualities of the oils of the order. Second, six to ten per cent, of resin. Third, angelic acid, one-third of one per cent., discovered bj Buchni in 1843, ami since found in a number of other plants, as well as made by synthesis; an odorous crystalline volatile acid. Fourth, a very small amount ol va- lerianic acid, together with the crystalline angelii an amaroid, and a little ea< h ol tarch, tannin, and sugar. Its properties are aromatic, stimulant, carmina- tive, and flavoring, as usual in the family. The dose is from 0.5 to 2 grains (gr. viij.-xxx.). A ml: lica oil from this source is an article of corn- ier American Angelica is the root of Angelica airn- purpurea L., a plant of very similar habit to the last, growing in Northeastern North America The tool ;i'"« in the same manner from a similar rhizome, but are marketed detached therefrom. They are some- what larger than those of the European, and arc of a light gray-brown color. The composition and prop- erties are practically the same, though the root and the oil have a perceptibly different odor and taste. II. II. Rusby. Angina Abdominis. — This term was apparently first used by Baccelli of Rome, according to Minella, ' who reported a case of this condition. The latter observer defines angina abdominis as a condition in which there occur paroxysms of severe abdominal pain, resulting from aneurysm or arteriosclerosis of the vessels of the celiac plexus. In Minella's ease at autopsy there was demonstrated an aneurysm of the celiac axis. The pain may be associated with the symptoms of angina pectoris, in which case the diag- nosis is not difficult. In other instances the pain is confined to the abdomen, occurs usually in elderly persons affected with arteriosclerosis, and is accom- panied by the feeling of impending dissolution. The subject of angina abdominis is discussed at length by J. Pal in his article " Ueber Angina Pectoris und Abdominis" 2 and in his book entitled "Gefass- krisen." 3 According to this author anginal attacks belong to the vascular crises. There are two types of angina: the pectoral and the abdominal. The latter is comparatively rare, but has been described by many clinicians, including Huchard,' Leydcn, Jaworski, Neusser, 5 and Pauti and Kaufmann. The vascular crises also include the abdominal crises of tabes and of lead poisoning. In all of these cases the pain is the result of the contraction of the blood- vessels of the abdominal viscera. In addition to the pain there is an inhibition of peristalsis. But the pain controls the clinical picture. Huchard also refers to the similarity of the attacks of angina abdominis to the gastric crises of tabes. In certain cases it is difficult to differentiate between the two conditions. In both of these the pain is severe and is localized in the epigastrium, but it may radiate widely from this region. On the other hand, Pauli and Kaufmann believe that the pain is localized in the visceral blood-vessels, and is the result of lesions of the inner lining of the latter. Their conception agrees with Nothnagel's views regarding vascular colic. Pal states that one is accustomed to localize abdominal pain in some definite organ. As a rule this localization is deceptive, for the objective locali- zation of pain is possible only if this symptom is accompanied by manifest lesions of the suspected organ. This difficulty is further complicated by the fact that the nerves of the abdominal viscera are not particularly sensitive, for gastric and typhoid ulcers may be present without giving rise to the slightest pain. Within recent years there have been describe. 1 cases of paroxysmal abdominal pain, which has been attributed to arteriosclerotic changes in the visceral blood-vessels, which changes in turn give rise to intermittent obstruction and ischemia. These 421 Angina Abdominis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cases have been reported by Markwald, Schnitz'ler, 6 Ortner, 7 and others. To this group belong the cases described by Ortner as the intestinal type of arter- iosclerosis, under the name "dyspraxia intermittens angiosclerotica intestinalis." According to Pal, the pain of angina abdominis is not the result of ischemia. He believes rather that the peripheral vasoconstriction is accompanied by a distention of the proximal arterial vessels. In this view Pal agrees with Colin, who attributes the pain to increased tension in the mesenteric vessels. That this theory is a plausible one is shown by the fact that the administration of drugs, such as the nitrites and nitroglycerin, which dilate the blood-vessels in other parts of the body, removes the tension in the visceral blood-vessels and relieves the pain. In all of Pal's cases there was a generally increased arterial tension. In most of the cases there was an increased and more widely diffused pulsation in the region of the abdominal aorta. An accompanying phenomenon of angina abdom- inis is constipation, which also occurs in the visceral crises of tabes and plumbism. In some cases tnere is a retraction of the abdominal wall, in others there is meteorism. There may also be a segmental dis- turbance of sensibility in the regions supplied by the lower dorsal and upper lumbar roots. The retracted abdomen of lead and tabetic colic is not as characteris- tic in angina abdominis, in which the condition is possibly masked by a hyperemic liver. Distent inn when it occurs is caused by an intestinal atony due to vasoconstriction, and may be compared to the dis- tention occurring in renal and biliary colic. Vomit- ing sometimes occurs as a secondary manifestation. Pal alludes to the fact that the vasoconstriction may affect only certain vessels of the abdomen. Angina abdominis must also be differentiated from neuralgia of the abdominal sympathetic. In this condition there is no evidence of increased arterial tension. Neuralgia of the abdominal sympathetic is probably identical with the "syndrome solaire aigu d'excita- tion" of Jaboulay. Pal s in his paper entitled "Zur Kenntniss der abdominellen Gefasskrisen der Tabetiker und ihrer Beziehung zur 'Aortite Abdominale' " states that angina abdominis may occur coincidently or al- ternately with angina pectoris. Many of Pal's cases suffered from tabes. This observer recognizes in the latter disease two varieties of gastric crises. In one of these the attack is purely gastric; there is vomiting with or without pain, and the blocd pressure does not rise to any marked extent during the attack. In the second variety of tabetic crises there is marked abdominal pain associated with high arterial tension. In these cases the pain comes on as the pressure rises and is relieved by amyl nitrite or the other nitrites. In his article "On Abdominal Pain" Sir Lauder Brunton 9 referred to an observation made by Dresch- feld of Manchester in a case presenting paroxysmal abdominal pain. At autopsy the only abnormal condition found was an atheromatous state of the intestinal vessels. In this article Brunton described a condition of paroxysmal abdominal pain occurring in individuals who are apparently otherwise perfectly healthy, whose digestion is good, and whose bowels are regular. Brunton attributed these attacks to irregular spasmodic contractions of the abdominal vessels analogous to the peripheral contraction and proximal dilatation of the temporal artery occurring in migraine, which latter condition Brunton had observed in his own case. For the abdominal pain, just as for migraine, he advised the use of salicylate of sodium and bromide of potassium together with carminatives and friction of the abdomen during the attack. Sir Lauder Brunton and W. E. Williams 10 report the case of a man aged sixty-eight years who had been suffering from diabetes for twenty-five years. For the previous eighteen months he had been 422 suffering from abdominal pains that had been at- tributed to flatulence, and that had been accompanied by marked loss of weight and drowsiness. The striking feature in this case was the severe spasmodic abdominal pain which came on about twice daily mostly after the exercise of walking or of playing billiards. An unmarried sister aged sixty-four years had also suffered from similar pains for the past seven years. The pain resembled that of angina pectoris but it differed in its localization, being most severe in the umbilical region. It gradually increased in severity and extent so that it spread all over the front and back of the chest and was fol- lowed by a profuse perspiration that broke out all over the body. The attacks were controlled by the administration of nitroglycerin. An interesting case of angina abdominis occurring in a patient exhibiting pronounced symptoms of cardiac insufficiency, is reported by W. K. Hunter." The case was that of a man aged futy-six years who was under observation in the ( rlasgi iw Royal Infirmary for one month previous to his death. The attacks of epigastric pain began eighteen. months before he was admitted to the hospital. The pain at first was dull and aching, usually began about one hour after meals, and was relieved by the taking of food. It was frequently associated with flatulence. Shortly before the patient was admitted to the hospital the pain had altered its characters, being now sharp and shooting. and coming on in a series of frequent paroxysms which had no relationship to the taking of food. There were marked loss of weight and slight jaundice, but there was no history of alcoholism or of syphilis. His previous health had been good. On examination, the patient was lying in the semi-recumbent position, very restless, with a good deal of dyspnea, and with occasionally a C'heyne-Stokes type of respiration. The pain in the epigastrium was more or less constant, with frequent and severe exacerbations, each paroxysm lasting about one minute. With each paroxysm the breathing was quickened and the face became cy- anosed. There was pronounced cardiac arrhythmia and the heart sounds were indistinct and of poor quality. The radial arteries were atheromatous. There were signs of pulmonary hypostasis, the liver was enlarged, the feet and legs were edematous, and the urine contained a small amount of albumin and easts. During the month the patient was under observation the paroxysms of pain occurred nearly every day at intervals of fifteen to twenty minutes, and would last about one minute. This would go on for an hour or an hour and a half at a time. At one time it was thought that the patient was suffering from hepatic colic. The pains seemed to be too frequent and to have occurred over too long a period of time to be due to gall stones. The stools moreover showed no evidence of the latter, and the jaundice lessened in intensity. The appetite was poor and the patient frequently complained of nausea. The signs of myocardial failure became more marked. The blood pressure was unaffected by the pain. '1 he systolic blood pressure ranged from 150 to 155 millimeters of mercury, except for a day or two just before death when it fell to 115 mil.imeters. The pain ultimately became so severe and the patient so noisy and restless that it was necessary to keep him under the influence of morphine. He died with all the signs of heart failure. At autopsy the heart was found to be hypertrophied and dilated, and the seat of myocardial "degeneration which was apparently due to the patchy sclerosis and narrowing of the coronary arteries. The aorta was the seat of wide- spaced patchy atheroma which also extended into the larger vessels. The lungs wire intensely congested and some pneumonic areas were present. In the tight lung there were a number of large infarctions, The liver was considerably enlarged with a certain amount of old perihepatitis. The gall bladder, REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angina Abdominis bile ducts, and pancreas were normal. The spleen, kidneys, ami stomach uVre congested, and in the Last- named organ there was a considerable number of small hemorrhagic ulcers. Hunter believes that the above case presented a up of symptoms and postmortem findings that is frequently mei with in angina pectoris, and that the 0C8 e corresponds very closely in its clinical and pal h- llogical aspects to the cases described by lliiehard under the phrase "angine a forme pseudo-gastral- giqiic." The slight amount of perihepatitis would not cause the pain and the possible role of chole- lithiasis was ruled out. The hemorrhages into the gastric mucous membrane were regarded as venous in origin, and a phase of the marked passive congestion of the viscera. It was very doubtful whether these hemorrhages could cause the pain and the author had not seen any ease of gastric ulcer with pain of such great severity and of as Ions duration as in the case reported, in which the pain had the characters of the pain in true angina pectoris. The pain had no relationship to the taking of food. It is pointed out that A. F. Hertz has shown that gastric pain even when associated with ulceration is not due to irrita- tion of the sensory fibers in the mucous membrane, 1ml is to be attributed to a sudden tension of the gastric muscle fibers, such as is met with in very e peristalsis. Hunter suggests that if the origin of the pain in angina abdominis is to be sought tor in the stomach itself, one must regard this pain as being due to spasmodic contraction in the muscle of the stomach wall. Indeed, quoting C. F. Hoover, 12 lie states that at the present time there is a tendency to attribute angina abdominis to some fault in the arterial supply of the stomach wall, and to discard the older view that it is a referred pain originating in the heart muscle or in the ring of the aorta. An analogy is pointed out between the pain of angina abdominis and that of intermittent claudica- tion, in both of which conditions, as in the case re- ported by Brunton and Williams, the pain is induced by a muscular effort of some sort. But in Hunter's case the pain came on independently of muscular exercise, without rise of blood pressure and with no definite relationship to the taking of food. This last fact would seem to rule out the possible causative factor of increased peristalsis in the production of the pain. Hunter agrees with Pal in the view that ischemia of one or more of the abdominal viscera is not a satisfactory explanation of the causation of angina abdominis. There is greater plausibility in Sir Clifford Allbutt's contention that in most cases the condition is caused by a painful distention of an aorta which is the seat of an inflammatory lesion. H. W. Verdon 13 advances the theory that the anginal habit, whether of the abdominal or thoracic type, results from a state of increased irritability of certain medullary and spinal centers, and the parox- ysm is excited by impressions reaching these centers from the muscular coat of the esophagus and stomach, when this muscular coat is in a state of hypertonus or tetany. This theory is based upon the author's observation of four cases of angina abdominis. In all of these cases there was pain in the epigastric region, which pain was associated with hyperesthesia. In three of the cases the seat of the hyperesthesia was the rectus muscle, and in one case the skin alone over this muscle was hyperesthetic. In two of the oases pain appeared simultaneously in the epigas- trium and in the arm. In all of these cases the dis- tribution of the pain together with the hyperesthesia can be explained on the basis that the pain is reflex or referred, according to the views advanced by Mackenzie, Head, and others. According to Verdon, fullness of the stomach whether occasioned by an excess of solids, fluids, or gases, seems to have no effect by itself in exciting a seizure, although it heightens the tendency to an attack. The attack is | usually excited by the act of walking soon after a meal, which muscular effort apparently induce- hy- pe] tonus of the gastric muscle. To recapitulate, the various theories that have been advanced to explain the causation of angina abdominis are as follows: aneurysm or arteriosclero i of the vessels of the celiac plexus; contraction of the peripheral blood-vessels ol the abdominal viscera with distention of the proximal vessels; le ion ol the inner lining of the visceral blood-vessels; ischemia due to arteriosclerosis of the bl I ve els <,f the abdomen; painful distention of the aorta which is the seat of an inflammatory lesion; and a state of hyper- tonus of the stomach induced by distention and bodily movements. The symptoms of angina abdominis are pain in the epigastrium, which may be associated with pain in other parts of the body; hyperesthesia oxer the region of the rectus muscle; a feeling of intense anxiety or of impending death, as in angina pectoris; increased arterial tension; and constipation. In the differential diagnosis the main conditions to be ruled out are angina pecti ris, the gastric crises of tabes, and lead colic. E. von Neusser 5 states that violent gastralgia or intestinal colic may be the only manifestation of angina pectoris. Other conditions to be considered are nervous gast ralgia; ulcer or cancer of the stomach; pyloric stenosis; duodenal ulcer; malignant disease of the intestines; ulceration, chiefly tuberculous, of the small intestine; intestinal stenosis; constipation; appendicitis; Dietl's crises; renal colic; tabes mesenterica; diseases of the liver, gall bladder, and pancreas; aneurysm of the aorta; neuralgia of the I abdominal sympathetic; and caries of the vertebral / column. Many of the points in the differential dia'g=^ nosis will readily suggest themselves; others have been dwelt upon in the preceding lines. The treatment which is practically the same as that for angina pectoris consists in reducing arterial hypertension by means of amyl nitrite, nitroglycerin, or any other of the nitrites. The hygienic and dietetic measures which are suitable for cases of arteriosclero- sis should be enforced during the intervals between the attacks. Jacquet 14 has obtained good results with the combined administration of iodide of potassium and nitrite of sodium, as recommended by Lauder Brunton. The latter has also advised the use of salicylate of sodium and bromide of potassium, along with carminatives. During the attack gentle massage of the abdomen may be employed. In the very se- vere attacks which cannot be controlled by either measures the hypodermic use of morphine may be I necessary. Alexander Spingabn. — References. 1. Minella: Gazzetta degli Ospedale et delle Cliniche, 1902, No. 120. 2. Pal, J.: Wiener medizinische Wochenschrift, April 2, 1904, page 570. 3. Pal, J. Gefasskrisen, Leipzig, 1905. 4. Huehard: Maladies du Cceur et de l'Aorte, Paris, 1S99, vol. ii., page 19; also Formes Cliniques de 1'Arterio-sclerose, Paris, 1909. 5. von Neusser E.: Clinical Treatises on the Symptomatology and Diagnosis of Disorders of the Respiration and Circulation, English Translation, Part III, Angina Pectoris, New York, 1909. 6. Schnitzler: Zur Symptomatologie der Darniarterienver- schhiss, Wiener medizinische Wochenschrift, 1901. 7. Ortner: Zur Klinik der Angiosclerose der Darmarlerien (Dyspragia intermittens angiosclerotica intestinalis), Sammlung klinischer Vortriige, n. f., Innere Medizin, No. 347. 8. Pal: Medizinische Klinik, 1908, page 1790. 9. Brunton, L.: International Clinics, 8lh Series, London, 1S99, vol. iii., page 111. 10. Brunton, L, and Williams, W. E.: Lancet, April 6, 1912 11. Hunter, W. K.: Lancet, July 6, 1912. 12. Hoover, C. F.: Osier and McRae's System of Medicine vol. iv., p. 288. 13. Verdon, H. W.: Lancet, June S, 1912. 14. Januet, A.: Zur Symptomatologie der abdominalen Arteriosklerose, Correspond. -Blatt fur Sehweize Aerzte, 1906. 423 Angina Ludovici REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angina Ludovici. — Various names have been applied to this affection. Among them may be men- tioned the following: acute phlegmonous pharyn- gitis, erysipelas of the pharynx, diffuse cervical abscess or phlegmon, submaxillary bubo, infectious submaxillary angina, sublingual abscess or phlegmon, subhyoid phlegmon, gangrenous induration of the neck, cynanche cellularis maligna, cynanche sub- lingualis rheumatica. As will be seen, these terms are not definite. In late years phlegmonous inflam- mations of the various regions of the neck and throat have been differentiated and given each its own descriptive name. Thus in a thesis by Broeckaert, of Ghent (Paris, 1909), the author refers to no less than fifteen different anatomical spaces, each one of which may become infected. While early writers asserted a specific individuality for this disease, later authorities regard it as a septic sore throat with a peculiar localization, not differing etiologically from phlegmonous pharyngitis, erysipelas of the pharynx, or acute edema of the larynx, all of which seem to represent merely different degrees of virulence of the same infecting agents. The question of primary development and localiza- tion depends probably upon the seat of original infection, and it is difficult to establish definitely a line of demarcation between the purely local and the less complicated, as distinguished from the edematous and purulent forms. The application, clinically, of general bacteriological principles to this group of septic inflammations harmonizes to a certain extent former conflicting views. Angina Ludovici is a diffuse phlegmonous inflam- mation of the floor of the mouth and of the inter- muscular subcutaneous tissue of the submaxillary and sublingual regions. It may end in resolution, abscess, or gangrene. Gerster defines it as a phlegmonous destruction of the submaxillary gland characterized by alarming and extensive dense edema, caused by the unyielding character of the fascial envelope of the gland, which edema is most manifest about the latter vicinity, namely, the floor of the mouth. Its possible epidemic character can be explained by the simultaneous exposure of various patients to the same septic influence. As a sequel to or com- plication of infectious maladies, it has been observed more often in typhus fever. As yet no special pathogenic germ of the disease has been found, and where examinations have been made only the ordinary bacilli of suppuration have been present. Of these the streptococcus is most frequently found. The staphylococcus is also often in evidence. It is only in respect to the site of the disease that it may claim special consideration. The location in which the pus originates is a triangular pyramidal space with the following boundaries: The apex (below) corresponds to the point where the mylohyoid muscle borders the genioglossus. The base (above) stretches along under the tongue. The external wall (oblique) is made up of the internal face of the inferior maxilla and the mylohyoid muscle; the internal wall (vertical) by the genioglossus and the hyoglossus. The mucous membrane of the floor of the mouth and the glandules sublinguales close its cavity on top. It is through this channel, however, that the infection gains entrance, so that the affection of the submaxillary gland is in many, if not all, instances secondary. The symptoms are constitutional and local. The former are in general those of pus formation, but it is important to bear in mind that the pathological process may also give a distinctly asthenic type of symptoms, with an overwhelming prostration and low temperature. The local symptoms, in addition to the prominent swelling of the neck, present the following diagnostic points: first, and most diagnostic of all, there is a 424 peculiarly hard and wooden-like induration of the affected region, sharply define'd from the surrounding normal tissue; second, the thrusting forward and upward of the tongue toward the palatal vault by the accumulating inflammatory products; third, severe dyspnea, with the possibility of laryngeal edema; fourth, the sensation of pressure as from a hard pad or button-like swelling at the inner aspect of the dental arcade. With all of these there are associated the ordinary features of a phlegmon. Swallowing is painful, if not impossible, on account of the muscular infiltration, and the patient may not be able to open the mouth. The prognosis is always grave and the rate of mortality high, one series of cases reporting over fifty per cent, of deaths. Death most frequently results from sepsis, or from suffocation due to laryn- geal edema. Diagnosis. — The condition must be differentiate ,1 from osteomyelitis of the lower jaw, simple adeno- phlegmon of the submaxillary gland, and the rare disease known as Fleiscliman's hygroma. In the first there is no limited focus of inflammation. The entire bone is affected, the inflammatory process is more generalized, and the subhyoid region is rarely involved. In the second, adenophlegmon, the in- flammation is superficial, the gland and its capsule are easily accessible, there is no wooden-like hardness, superficial ineison gives exit to pus, and the process is localized at the outset behind the internal face of the maxilla. In the third the diagnostic points are suddenness of onset, location in the median line, and lack of either constitutional or local evidences of inflammation. In Angina Ludovici the diagnosis may be made from the symptoms described above. To these must be added two signs of great importance: fust, pain on pressure over the focus of the inflam- mation; and second, the withdrawal by aspiration from the focal region of a bloody fluid. These signs call for immediate operation, never by limited incision, but always by careful and thorough dissection. The treatment must be based upon three principles: First, early and free incision; second, careful sub- sequent antisepsis; and third, constitutional support. The condition is one of sepsis. The cause must he removed, and the effects already produced must be vigorously counteracted. Gerster demonstrates that the object of the incision is not so much to evacuate pus as to relieve tension. He supports the modern view that the submaxillary gland is the focus of the disease, and attaches much importance to the fact that pressure over the edema- tous area rarely causes pain except directly over the gland. If such evidences appear, delay in operating is not justifiable. The operation must be done under general anes- thesia, for deej) tissues must be explored in close proximity to important vessels and nerves. Fluctuation may be delayed because of the pus being confined within a fibrous capsule. Early incision may evacuate nothing more than an ichorous discharge, while pus may form later, but tension i- thus relieved and the consequent dangers of suffoca- tion are much lessened. Deep lateral incision over the submaxillary gland, operation through the mouth, and even external incision in the median line are all to be condemned. The most satisfactory method is that suggested by Gerster, namely, to lay bare the entire submaxillary region by a careful dissection before making the incision for evacuating the abscess. To be effective the incision must penetrate the mylohyoid muscle. Following incision irrigation with bichloride (1 to 1,000) or boric acid (1 to 100) must be carefullj carried out, and stimulants and tonics administered according to indication. The application of cold to REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angina Pectoris the neck, if of any value at all, can be of service only in the very earliest stages. Hydrogen peroxide may assist in the separation of the slougns. The value of vaccines and serums in tins condition lias not yet been demonstrated, although in other somewhat analogous infections due to the strepto- coccus, hopeful results arc being obtained. (Ball, (, June 8, 1!)12.) Prophylaxis. — To guard against the occurrence of Angina Ludovici, the mouth, pharynx, and nose should be kept carefully cleansed in all eases of dis- ease, such as typhus fever, in which infection of the sublingual region may take place. Recently some forms of grippe have shown a tendency to generate ical phi union. Here again and in all allied litions of the mouth and throat proper aseptic precautions may avert many possibilities of danger. D. Bkyson Delavan. Angina Pectoris. — Angina pectoris is a convenient name for a group of .symptoms in which the pre- dominating feature is pain of varying degrees of intensity over the precordial region, occurring in paroxysmal attacks, occasionally prolonged to be- come chronic, and in rare instances associated with the subjective symptoms of impending death. The pain may originate in distant organs or in the precordial region itself, and from this point radiate in various directions, usually to the left shoulder and arm, sometimes to the right: occasionally to both .shoulders and arms. There are two main divisions of angina pectoris, the true and the false. In the true form, or angina vera, there is an anatomical basis in the heart itself; the false form, or pseudoangina, is a neuralgia of the heart . In the true form, affections of the coronary system are noteworthy among the pathological findings, while other degenerative changes, in either the aorta or its branches, in the endocardium, or in the walls of the heart, may be more nearly related to the cause of the attacks. Although the name angina pectoris does not de- scribe the essence of the disease, it is likely to be re- tained, because, theoretically at least, it covers a perfectly recognizable group of cases, that may, in the majority of instances, be relieved and usually cured by appropriate management. For though true angina is a dangerous disease, with a very un- favorable prognosis, it is extremely rare. False angina, on the contrary, is very common, if we in- clude under the name all the minor forms; and it is amenable to treatment. The etiology of the two forms is different also, though unfortunately they cannot always be differentiated, and occasionally may be combined. At no time, however, does the angina kill. If death occurs, it must be attributed to an underlying organic disease. True angina pectoris came to be generally known in France and England as early as 1768, though it had been described some years earlier by Morgagni, as to both its clinical and pathological features. In the year above mentioned, Heberden was the first to differentiate it from cardiac asthma, a distinction that is not always maintained at the present day. In 1772 .leaner and in 178S Parry noted the coincidence between sclerosis of the coronary arteries and angina pectoris. Angina pectoris motoria was described by Landois in 1866. He held it to be an exaggerated vasomotor disturbance causing increased arterial pressure, or vasomotor paresis, and to be found in chlorotic and anemic girls in emotional or cerebrospinal crises. Niemeyer held the same view, and Nothna- gel recognized this form also, having seen it in cases of exposure to cold. Bamberger held analogous ideas. This is a variety of the false form. Angina sine dolore is the m given to an attack where there is a feeling of constriction of the chest without pain. Another division of angina pectoris has been into the smrf and mild forms. Hui this classification is in. i satisfactory, because it misleads as to results. A severe at lack may be of the pseudo form, or a mild uiie of the true variety. i have seen a ease of the former where the pain was intensely excruciating, and in other instances attacks of the true form that were comparatively mild. In ls7:'., the distinction between true and false angina was emphasized by Walshe. This distinction is essential, because on the differential diagnosis hang the prognosis and the treatment. Statements \ ary as 1" the frequency of true angina. In England it is not regarded as an unusual disea I - However, in a series of 823 cases of my own, fairly complete as to clinical histories and autopsical findings, and covering an experience of ten years in one hospital and fifteen in another, I did not find mention of a single case of true angina pectoris. And in a series of 2,31 » i medical eases treated by one of my colleagues at the Post-Graduate Hospital, there was not a single ease of true angina recorded. Another of my colleagues, who had an even larger experience in the outdoor medical department of Bellevue Hospital, did not remember having seen during the years of his service a case of true angina. In this vicinity at lea-i, therefore, true angina is a rare disease. There has been a tendency to attribute true angina to coronary disease with sclerosis, with or without embolism or thrombosis. Gautier and Huchard in a series of seventy cases found coronary disease in thirty-eight, or about fifty-three per cent. In a later series Huchard found coronary disease in 128 out of 145 cases, or eighty-eight per cent., but evi- dently the myocardium was not subjected to a close examination. Coronary disease without angina is common. Indeed, coronary disease between the ages of fifty and sixty is the rule. And yet as I have said it may exist without any symptoms of angina. In fact, I should be quite willing, from own experience, to say that I have seen hundreds of cases of coronary disease at autopsies where clinically there had been no symptoms of true angina, and I believe that the best of our modern pathologists will subscribe to this view. In fact, Romberg in his recent work admits that angina is frequently absent in coronary disease, though he maintains that there is usually a localized contraction of the arteries round about the points of their origin. Embolism or thrombosis he believes may cause attacks, and this view is well sustained by evidence. Etiology. — In order to realize the diversity of opin- ion as to the etiology of angina pectoris, a brief review is necessary. In 1768 Heberden broached the idea that the pain was due to the contraction of the heart, which being a hollow organ suffered from pains some- what analogous to those of other hollow organs, such as the intestines and uterus. This theory is now main- tained by Mackenzie in a modified form. But accord- ing to this theory there should be violent alterations in the rhythm of the pulse, which I have not found. There is undoubtedly some hypertension, however, in the early part of attacks. However, Parry, Stokes, and Traube claimed that the pain was due to cardiac paralysis, Traube holding that there was acute dilatation which caused laceration of the cardiac nerves. Of course, there is no doubt that if death impends in true angina there is cardiac paralysis. Some have held that the attacks are manifestations of lithemia, and I am inclined to believe that in lithemie cases there can be a fibrosis of the heart inn cle that may have to do with the pain. Laennec and Lartigue referred the pain to the pneumogastrie, while Lancer- eaux, Peter, and Bazy laid it to infiltration of the 425 Angina Pectoris REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cardiac plexus. But as a matter of fact infiltration of this plexus by the new growths does not always produce pain, and if this latter view were correct the pain should be continuous, not spasmodic. Friedreich thought it a functional affair, a neurosis. Trousseau compared angina to the nerve explosions of epilepsy; Bouillaud ascribed the pain to phrenic and intercostal irritation; while Piorry called it a brachiothoracic neuralgia. Allan Burns referred it to the distention of the cardiac vessels, and Lauder Brunton similarly ascribed it to the overdistention of the coronary vessels. This latter theory might apply in pseudoangina, but could not in cases of stiffness of the coronaries, which characterizes the progressive stages of the disease. Nothnagel advanced a theory that the pain was due to spasm of the vasomotor nerves of the heart. Josueand Allbutt have held that the pain is located in the aortic ring. Romberg in his latest edition was inclined to think with Charcot and Erb that angina is related etiologically to the diminish,! I supply of blood occasioned by the narrowed lumen of the degenerated coronary vessels. According to his theory, while under ordinary circumstances there is a sufficient blood-supply to the heart to admit of its functions being satisfactorily performed, under the operation of certain physical and psychic influences the relation between the blood-supply and the heart muscle may be disordered sufficiently to cause pain. In this connection, it is important to know that the coronaries terminate in comparatively large trunks from which capillaries are given off, and that these unite to form reservoirs between the muscle fibers, while the capillaries freely anastomose, so that inter- ference with the circulation within a cardiac artery means interference with a large amount of capillary tissue. As a result of this anatomical peculiarity of the capillary system, its contractions might cause sensations of pain quite unlike those of any other organ in the body. It will be noted that in the summary of veiws given above as to the cause of the attacks, little distinction was made between the true and the false forms. In- deed, although for excellent practical reasons we may recognize tin- two, it may well be that in all cases the cause of the pain is neuralgic. In one of my patient - who had false angina (where the treatment was even- tually so successful that she has now for about ten years been enjoying life, with only an occasional intimation that she has a heart, the apex was brought in by treatment one and five-eighth inches, and was con- tracted as well), I believe the pain was located in the nerves of the heart walls, and arose from dilatation. It may arise also from compression, as from a dis- tended stomach, a very common occurrence in people who are comparatively well. Recent physiological studies have shown us that there may be irregular contraction of the walls of the heart at times, i.e. local spasms. Besides, in fibrosis of the heart walls, which seems to be sometimes a feature of the lithemic heart, there must be unequal contraction of the muscles. Any ime of these conditions may cause unequal ten- sion of the walls. This theory I proposed some years ago. The pain may originate either from disease of the heart or great vessels, or from a remote locality. But how are we to explain on the ground of the unequal tension theory the fact that coronary disease is an important factor in the causation of angina? The answer is that coronary disease may be a cause of degeneration of the heart because it diminishes the supply of blood, the result being that weak spots are developed in the cardiac walls in areas where the nourishment is imperfect. Again, fibrosis eventually takes the place of infarcts. The heart muscle cannot therefore contract evenly, and the uneven contraction causes the pain. Charcot held the view that it was due to local spasm, similar to the local spasms of the intestine in influenza, the fibrillary contractions of facial muscles in cerebral disease, or the spasm of the muscles of the extremity in the "intermittent claudi- cation" of Bouley, the veterinarian, who first saw it in horses. After a number of these attacks, there is left in the cord a susceptible area, which is prone to originate successive attacks. Among the lesions that have been described, it is noticeable that coronary diseases have a rather large place, while atheroma of the large vessels, aortic endocarditis, pericarditis, and myocardial disease have been subordinated. However, there has been a tendency of late to look upon the myocardium as the chief tissue implicated. High pressure is re- garded as one of the determining causes of an attack, but it may be the result as well. In the later stage- of an attack, a normal or subnormal pressure i occur. The exciting causes may be disturbance of the function of any organ or system. I have known in a single instance that one at tack was excited by conges- tion of the kidneys, a second by obstinate constipation, and a third by overloading of the stomach with in- digestible food. Unusual muscular activity may also be a cause, while in the false variety emotional causes. a sudden impression on the sensitory nerves, walking in the face of a sharp wind, or toxic causes such as the use of tobacco, tea, or coffee, may bring on an attack. While the incitement to an attack of angina vera may be from the heart itself, as in a sudden attack of cardiac embolism, or from without, usually from an abdominal organ; in the false form the seizure origi- nates from a point without the heart. True angina is more frequent in males. Pye- Smith found the proportion seven to one; Huchard about five to one. On the other hand, the pseudo cases are much more common in women. Huchard found the proportion three to one in favor of women, and the proportion is undoubtedly much higher in this country. True angina rarely occurs before forty years of age: in Forbes' eighty r -four cases, seventy- two were over fifty, or eighty-six per cent. Symptoms. — In an attack of true angina, the pain is referred to the sternum about its middle. From this point it may radiate to the left shoulder and arm, to the right, or, occasionally, down both shoulders and arms. In a well-marked case the face will be pallid, and the forehead covered with sweat, while the rate of respira- tion, in uncomplicated case-, may either be incrr or remain unchanged. This condition of the respira- tion contrasts sharply with the increased rate of the cardiac asthma in valvular and myocardial disease. Toward the end of an attack, or after successive attacks, a somewhat increased rate of respiration may be expected. If the patient gets relief promptly, the respiration should fall to the normal. Inasmuch, however, as the increased action of the weak heart is likely to produce more or less stagnation of blood in the pulmonary cavities, there will be in such a case a proportionate increase in the respiratory rate. While the heart's rate may be increased or unaffecti d, in mild cases it is apt not to be changed. _ There is, how-ever, usually some degree of arrhythmia. Blood pressure is usually increased, and Mackenzie reports that he has found it as high as 200. As the attack passes off, there is a sense of weakness proportionate to the severity of the seizure. During the attack there may be great belching of wind, while the urine voided is apt to be of a very low specific gravity. In a case where the neurotic element is well marked, these two latter signs may be pronounced. The pain is a distinctive feature of true at It is the pain of an intense neuralgia, so excruciating that tin- patient feels that he must keep absolutely still until it has passed. In my experience the " sense of impending death" has not been a prominent feature, but on several occasions the patients have expressed themselves as feeling that the chest was lieing compressed, as if in a vise. In one instance the 426 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angina Pectoris patient said she felt as if ":i house wen- resting mi her chest." But then' are degrees in the amount of pain felt. Tin' attack is visually brief c especially after the first attack, for then the patient's experience ha< taught him or her how to manage the seizure. But while it is usually of only a few 9 mis' or minutes' duration, it may last several hours, and in One of my eases an intense angina continued for eral days. This constituted what is called the *is anginosus. The immediate cause of an attack may vary, as has already I n mentioned. In one of my pseudo sit was produced by sexual intercourse, in a not her by the smell of fresh paint, and in a third by pro- longed conversation. A common cause is undue hurry, or walking in the face of a sharp wind. Death in true angina has been ascribed to defective tabolism. This may be a contributing cause, for if the disease is associated with uremia the muscular e "f the organ may be paralyzed by the toxemia. \\ e may safely assume t hat actually death is due to the disease of the heart walls resulting from exhaustion or defective innervation. The heart comes to a standstill simply because it is worn out. Diagnosis. — All of the circumstances of a case must be carefully considered in making a differential diag- nosis, and it will not always be easy, because the nature and gravity of the underlying disease may not at first be readily determined. If in the male sex, after fifty years of age, and in association with general arteriosclerosis and some form of heart dis- ease, particularly of the aortic valve, or pronounced evidences of the lithemic diathesis, the diagnosis of true angina may be made with a considerable degree of confidence. On the other hand, in young people, especially women, and those of neurotic history and lowered vitality, in the absence of arteriosclerosis or any form of heart disease, the diagnosis of pseudo- angina may be made with an equal degree of confi- dence. Then, too, in the false angina from poisoning by tobacco, tea, or coffee there is a history of indul- gence in these luxuries, with their associated cardiac and neurotic symptoms that cease when the cause is removed. As regards the differential diagnosis from cardiac asthma, in the latter there is actual dyspnea, while in uncomplicated cases of pseudoangina there is never any actual dyspnea, for the patient can draw a long breath if he makes the attempt. In cardiac asthma there is engorgement of internal organs, and externally there are physical signs of venous congestion. Treatment. — Nitroglycerin, given by the mouth in doses of at least T J to^j grain, is indicated. I do not hesitate to give Jj every two minutes for ten minutes to abort an attack. If the patient can swallow, the desired effect is produced more quickly by oral administration than by hypodermics. A few drops of the nitrite of amyl given on a handker- chief may relieve mild attacks, and the delicate glass capsules containing three or five minims of the drug, which can be crushed in the handkerchief, are con- venient for administering it. But the nitrite of amyl alone is not always effective. I give it inter- nally also, as in the following prescription: . Glonoin grain 1J3 Amyl nitrite grain i Menthol grain 53 Oleoresin of capsicum grain iha Place in air-tight gelatin capsules. S. One at a dose. When properly made, these capsules are effective in mild attacks. Unfortunately the ingredients are not -table. In cases where these remedies are not at hand, morphine should be used, followed up, without wait- ing for its action, by inhalation of chloroform or ether. The patient may pour a few teaspoonfuls of ether into a, saucer and inhale the fumes. Bal- four's plan i- to put a sponge "il.ed m chloroform in- to a. wide-mouthed bottle, and allow the patient to inhale the fumes until relief is obtained. Heat ap- plied to the chest by a hot-water bottle or bag, replaced by mustard leaves or poultices, will often give relief. If there is any sign of heart failure, brandy, whiskey, or ammonium carbonate is indicated, the latter being almost universally applicable. Digitalis] too low in its action to be useful during an attack, but is valu- able afterward. The aromatic spirit of am nia is often of great assistance, and also promotes the expul- sion of gas. After the paroxysm has passed, aconite will be found useful, in two minim doses, t.i.d., to regulate the pulse. In rass where there' is arterio- sclerosis, arsenic should be kept up for a while, and then replaced by potassium, sodium, or strontium iodide in doses of from five to ten grains, or even more. In rheumatic or gouty cases, a prolonged use of the iodides gives good results. In the pseudo cases Hoffman's anodyne is indicated, the valerianate of ammonium, the monobromate of camphor in one or two grain doses, or asafetida in doses of from three to ten grains. I sometimes give a thirty grain powder containing equal parts of the ammonium, potassium, and sodium bromides. Some prefer the nitrites. They are used extensively in England and France. The nitrite of sodium is preferred, and the dose is from one to three grains, given cautiously. In one of my cases I gave entire relief by the use of the continuous current. In true angina, as soon as the paroxysm has been relieved the treatment should be that of heart failure, or, in other words, enfeeblement of cardiac action due to the strain on an exhausted heart. Nothing equals the use of digitalin and strophanthin, which should be given together with glonoin in doses of one one-hundredth grain each, at first administered every four hours, and later after the pulse has fallen below the hundred mark, three times a day. This trea tmentmay be kept up for weeks or months without discomfort to the patient, provided the amounts of the several drugs are increased or decreased according to indications. Nothing but the very best makes of digitalin and strophanthin should be used. The tinctures and fluid extracts of digitalis and strophan- tus should not be used. Owing to the inflation of the stomach in these seiz- ures, it may be desirable to pass the esophageal tube. This has been practised successfully by Verdon in several cases. It is called gastric deflation. In such instances a sudden attack of vomiting may bring the seizure to a close. Where an attack is associated with constipation, an active cathartic will accom- plish the same result. Protracted rest in bed after a severe attack may materially aid in warding off another seizure. Car- bonated baths and resistant exercises are also effective. The diet should at the same time be carefully regulated. If uremia has superinduced the attack, a course of milk diet, in which the patient may take as much as two quarts per day, may relieve the uremia and restore the patient to comparatively good health. One must guard, however, against overloading the stomach with milk, and remember that many persons cannot digest much milk. Usually sufficient lime water should be added to prevent curdling. Coronary disease of itself is quite compatible with a long life, so that we must look beyond it for the cause of angina. And the evidence is increasing day by day that it is disease of the myocardium that determines angina vera. A single attack, as in embolism or thrombosis of the coronary arteries, may cause death. Also, if, after the age of fifty, anginal seizures become more and more frequent in persons with arteriosclerosis, fatty heart, disease of the great 427 Angina Pectoris REFERENCE HANDBOOK OF THE MEDICAL SCIENCES vessels, such as aortic aneurysm, advanced lithemia, or uremia, the prognosis cannot be other than grave, and the danger will be increased if there is a neurotic element superadded to these conditions. But even in these cases the expectation of life will be improved provided the patient can avoid cold weather and excitement, commits no excesses of any kind, and lues a methodical life, free from hurry and -worry. For any one of these exciting causes may bring on an attack which may lead rapidly to a fatal issue. The violence of the attacks is not always a measure of the gravity of the disease. On the other hand, in pseudo- angina, which is not only very frequent, but at one time or another affects most of us in the course of a long life, the prognosis is not grave. Under this head I classify the reflex vasomotor angina of Landois, which is associated with visceral and peripheral dis- turbances without any gross heart lesions, and also the so-called angina sine dolore, where the sensation is constriction rather than pain. These cases are in the class with hysterical seizures, hyperesthetic areas, and peripheral neuralgias. All we have to do in these instances is to control the neurotic symptoms, and we control the angina. There is seldom much diffi- culty in accomplishing this result by the use of such remedies as have already been enumerated. Thomas E. Sattekthwaite. Angina Vincenti. — Synonyms: Plaut-Vince nt angina, ulcerative angina and stomatitis, ulcero- membranous angina and stomatitis, angina diphthe- roides, angina exudativa ulcerosa, angina chanci- forme, pharyngitis ulcerosa, pseudomembranous an- gina, "spiroehatenbacillen Angina," gangrenous ton- sillitis, "ulcerative sore-throat," "septic" and "pu- trid sore-throat". This is a peculiar form of tonsillitis or stomatitis in which pseudomembranes are formed upon the affected mucous surface, usually, but not always, with the production of a characteristic ulcer, and containing in the exudate the so-called fusiform bacillus of Plant and Vincent, usually in association with long spirilla. Vincent's name is not properly applied to this condition, as it had been previously described by a number of French and Russian observ- ers (Bartliez and Sanne, Simonowsky, Nevejin, Moure, and Mendel), and the association of fusiform bacilli and spirilla in ulceromembranous angina had been noted in 1893 by Rauchfus. In 1894 Plaut described the organisms in five cases of ulcerative angina as "Miller's spirochetal" and "Miller's bac- illi," giving Miller the credit of having observed as early as 1S83 the association with spirochetes of a bacillus longer than the diphtheria bacillus and pointed at the ends. He states that .Miller had found these on the edge of inflamed gums, and in an abscess of the finger-tip caused by a laceration by artificial teeth, and also in an abscess of the submaxillary gland. In 1896 Vincent described fusiform bacilli and spirilla in cases of hospital gangrene, stating that, similar organisms could be found in ulcerative angi- nas. Bernheim in 1897 reported thirty cases of stomatitis and angina in all of which fusiform bacilli and spirilla were present; and he is apparently the first to show the etiological identity of certain forms of angina and stomatitis. In the next year Vincent reported observations of fourteen cases of ulcero- membranous angina characterized by the presence of the same fusiform bacilli and spirilla; and it is due to tins accurate and complete study that his name has become associated with this form of angina and with the fusiform bacillus, which is also known as "Bernheim's bacillus" and the "Plaut- Vincent bac- illus," ''bacillus fusiformis," " bacillus hastilis," "spin- dle-shaped bacillus," etc. Observations upon these organisms and their association with ulceromembranous angina and va- rious morbid conditions have accumulated rapidly in recent years in German, French, American, and English literature, thus showing their widespread and frequent occurrence. They have been found in hospital gangrene (Vincent, Matzenauer, et al.), in noma (Matzenauer, Seiffert, Perthes, Rosenbergcr, and many others), in fetid abscesses about the mouth (Veszpremi, Silberschmidt, and others'), in fetid sub- pectoral abscess, fetid pleurisy, mastoiditis, laryngitis, bronchitis, bronchiectasis, abscesses of liver, lungs, and spleen, phlegmon, cerebral abscess, appendicitis, gangrenous ulcers of the penis, in syphilitic lesions of mouth and throat, in nasal discharges, and in the intestinal contents of a dog affected with dysentery. In the great majority of these conditions the two organ- isms are found together, but in some instances the > % . i / \ \ ! \ A \ \ i V *> . N ( ; \ \ \ \ \ V V f\ * Fig. 239. — Fusiform Bacilli and Spirilla in a Throat Smear fn.m ■a Case of Vincent's Angina. (From a Text-Book of Bacteriol by Hiss and Zinsser; D. Appleton and Company, New York.) bacilli alone are present. Other bacteria, particularly cocci, are usually present also; although in some cases the bacillus alone, or in connection with the spirillum occurs in pure culture. Both organisms also are found in the mouth of healthy individuals, while similar spirilla without the associated bacilli have been found upon the normal genitalia and in the vaginal secretion. The presence of the organ- isms in all of the conditions named has usually 1 een determined by the microscopic examination of smears, and occasionally of stained sections of tissues, i.f- forts at cultivation have usually failed, but both organisms have been grown in mixed cultures, and the fusiform bacillus in pure culture by a number of observers (Angelici, Gross, Niclot and Marotte, Seitz, Silberschmidt, Veszpremi, Seiffert, Perthes, Pruning, Netter, Veillon and Zuber, Ellermann, and Weaver and Tunnicliff). 428 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \n:-iii.i Vincent! Character of the Organisms.— As obtained in smear-preparations the reported descriptions of the bacilli and spirilla correspond very closely. The bacilli appear as long slender rods, pointed at the ends and somewhat larger in the middle. They vary greatly, sometimes the rods are thick with uled i- m"ls, sometimes they are slightly bent or may be S-shaped. They are six to twelve microns long, but longer thread-like forms are occasionally seen. They occur frequently in end-to-end pairs, often forming re or less obtuse angles, but may be nged in rows, or in clumps, or in radial ins groups. Observers differ as to their inutility, the majority describing them as no! motile. Graupner described peritrichous flagella, and found that motility was quickly lost. According to Ellerman the .short curved forms are motile spirilla. I he bacilli stain well with carbolfuchsin, Loeffler's methylene blue, anilin-water gentian violet, and polychrome methylene blue, but do not stain with Gram's, although some writers state that prolonged action of alcohol is necessary for complete decolori- zation. Babes-Ernst granules are not present, and there is no staining with Lugol's. Spores have nut been demonstrated, although light-staining as ("vacuoles") have been described. Pure cul- tures of the bacillus have been obtained by Ellerman (1904) and Weaver and Tunnicliff (1905), as a non- motile, obligate anaerobe, growing best at 30°, but nut at room temperature. Horse-serum agar, ascites agar, dextrose-free broth, plain agar, ascites broth, horse-serum give growths of the bacillus. The cultures may have an offensive odor, but no gas is formed. The spirilla are long and delicate with three, six, or eight turns. They stain lightly and uniformly, and are quickly decolorized by Gram's method. They are usually motile, but. may quickly lose their motility, especially when exposed to cold. They have been grown only in mixed cultures. Weaver and Tunnicliff used human pleuritic exudate and broth, and broth containing muscle-sugar. The growth was always slight, and was not influenced by the exclusion of oxygen. Veillon and Zuber, and Ellermann also, with inocu- lations of pure cultures of Bacillus J'usijorntis caused small abscesses in rabbits and guinea-pigs. Weaver and Tunnicliff produced abscesses in guinea-pigs by intramuscular injection of mixed cultures. Mixed cultures containing a growth of fusiform bacilli and spirilla with cocci also produced abscesses in guinea-pigs. Similar results were obtained with bacilli and cocci without the spirilla. Relation of the Organisms. — The majority of writers believe the fusiform bacilli and spirilla to be different varieties of bacteria acting in symbiosis, the virulence of the bacilli being increased by the presence of the spirilla. Numerous observers have noted that the cases of angina in which the bacilli alone are found are of a milder type than those in which both are present. In cases of deep destruction of tissues the spirilla are always present. Some writers (Seiffert, Perthes, Sobel and Herrman, and Krahn) believe that bacillus and spirillum are developmental stages of one organism, but there is no positive proof of this. Only a few writers (Bliihdorn) are inclined to regard the spirillum as the etiological agent, basing this view upon Rumpel's and Gerber's successful treat- ment of the angina with salvarsan, this being taken as evidence of the spirochetal nature of the infection. That the fusiform bacillus is the essential etiological agent in the conditions in which it is found remains yet to be positively demonstrated. The strongest evidence in favor of it is the demonstration in the tissues from cases of noma and ulceromembranous angina of filamentous organisms that resemble the cultural forms of the fusiform bacillus. Ellermann has demonstrated the presence of both fusiform bacilli and spirilla in the zone separating necrotic and living tissues in a case of gangrenous stomatitis. He also found the fusiform bacilli alone in the tissues ui the uvula from a case of ulceromembranous angina. The must recent writers regard the organisms as saprophytes under ordinary conditions, but like the colon bacillus, becoming primarily or .secondarily pathogenic under certain conditions. Predisposing Causes. — Although the infection with the fusiform bacillus may occur in apparently normal individuals, the majority of observers agree thai certain predisposing factors are usually present. Tobacco, defective teeth, tartar, inflamed gums, oral uncleanliness, alveolar abscesses, scurvy, syphilis, mercurial stomatitis, trauma of the inucuus mem- branes following tonsillotomy and other operations in the mouth, and primary infections with other organisms are regarded as predisposing factors. The condition is often associated with or follows the acute infectious diseases (scarlet fever, dipht heria, measles, and whooping cough). An epidemic of Vincent's angina, may follow one of diphtheria, espe- cially in institutions and hospitals, and under such conditions the bacillary angina is likely to run a more severe and malignant course. Contagion*. — Vincent's angina is regarded as directly ami indirectly contagious within rather narrow limits. The affection often involves definite, groups of students living in close association. A similar group-infection of nurses and hospital attendants has been observed. Institutional epidemics occur. The infection may be spread by the use of common eating and drinking utensils, towels, dental instruments, etc. Buhlig calls attention to the possibility of transmis- sion through the purse-string tobacco bag, the strings of which are often drawn tightly with the teeth. As a rule close contact is necessary for the spread of the infection. Occurrence. — The report of cases from all parts of the world show the wide distribution of the infec- tion. While many observers regard the angina as rare, it certainly is not an infrequent condition, and the most recent writings upon this subject regard it as of frequent occurrence. Rodella found the fusi- form bacillus in one-third of 2,000 cases of pseudo- membranous angina. Holm in 20.) cases of suspected diphtheria examined in 1908 at the laboratory of the Michigan State Board of Health found the fusiform bacillus present in seventy-three cases (thirty-three males, forty females). Of the seventy-three cases twenty-eight had been diagnosed as diphtheria clinic- ally but the diphtheria bacillus was found in only one of the twenty-eight. In over three-fourths of the cases of pseudodiphtheria the fusiform bacillus and spirilla were found, usually in association with staphylococci and streptococci, as shown by culti- vation. Smears from these cases showed the bacillus fusiformis as the most prominent organism. Bliih- dorn examined the throats of 222 patients for fusi- form bacilli and spirilla, and found one or both organ- isms present in all but twenty-seven out of seventy- six cases of diphtheria, in eleven cases out of forty- two of scarlatina, in thirteen out of twenty-six eases of staphylococcus or streptococcus sore throat, in two out of four cases of ulcerative si atitis, in twenty-one out of thirty-one cases of syphilitic sore mouth or throat, and in all but eighteen of forty healthy persons. In healthy persons the organism is found close to the teeth, and it is probable that it is responsible for certain ulcerative conditions of the gums. Other writers confirm the frequent occurrence of the organism. As to the angina males and females are equally affected, although some writers give a preponderance of cases in the male. It is common in children and young adults, but also frequent in middle life and in old people. It occurs more often in the spring than in the autumn. 429 Anelna Vincent! REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Pathology. — The local lesions vary from a slight exudative inflammation to an ulceromembranous, or even gangrenous process. One tonsil, more frequently the right (Koplik), is first involved, but after a few days the process may spread to the other. Many cases are unilateral. A gray, grayish, yellow, gray- ish-yellow, greenish-yellow, creamy, or dirty brown membrane appears upon the affected tonsil, varying in size from a lentil to that of the entire tonsil. Be- neath the membrane is formed the ulcer; from the first the base of the ulcer appears as if covered with membrane. The ulcer is rather chancroidal in type. with worm-eaten base and sharp overhanging edges which may be slightly elevated above the surface of the tonsil. Depth of ulcer varies greatly, from one- eighth to one-half inch or more. On removal of the membrane the ulcer bleeds freely and a new mem- brane may be formed. In the majority of cases the membrane does not spread, as in diphtheria; but in some cases it may spread rapidly and involve uvula, palate, gums, pharynx, larynx, or trachea. Sloughing of the uvula and soft plalate may occur. More rarely the ulcer is very destructive, the process becoming gangrenous or noma-like in character. The entire tonsil may be destroyed, and the necrosis may extend to healthy tissues. An ulcerative stomatitis is often present, and ulcers may occur in the tongue, cheeks, and gums. As a rule the ulcer heals slowly, and not infrequently becomes subchronic or chronic in char- acter. The submaxillary glands are often enlarged, as are the lymph-nodes at the angle of the jaw. Suppuration of these nodes is uncommon. Complications and sequeke in the form of middle- ear disease, mastoiditis, meningitis, cerebral abscess, bronchitis, pneumonia, edema of the glottis, pleuritis, empyema, pericarditis, arthritis, etc., may occur, but are relatively rare. In all of these conditions the pus has usually a characteristic stinking odor, similar to that produced in mixed cultures of the fusiform bacillus. Microscopically the ulceromembranous lesions show the picture of a necrotic inflammation. Fusiform bacilli and spirilla are found in the zone between the necrotic and living tissue. Symptoms. — The symptoms var}"- greatly, just as the local lesions differ in severity and extent. Many cases are very mild, others very severe. The infec- tion may occur without any symptoms. There are no characteristic prodromal symptoms. A feeling of dryness or discomfort in the mouth, followed by dysphagia and lassitude, restlessness, insomnia, loss of appetite, headache, coated tongue, constipation or occasionally diarrhea, vomiting, pain in the stomach, epistaxis, chills, and fever gradually develop during one to five days, when the local condition is discovered. The fever is usually slight, rarely higher than 103°. A marked fetor of the breath is often present, especially when there is an accompanying stomatitis. Some cases show a pallor of a distinctly septic type. The average case gives only the ordinary history of sore throat with ulceration. The cases with stomatitis may show bleeding from the gums, and the teeth may become loose. Earache and nasal discharge are not infrequent. In the severe eases the symptoms may be very violent; there is great pain and difficulty in talking and swallowing, the breath is very fetid, the cervical lymph-nodes are enlarged and tender, there may be marked gastro- enteritis, high fever, and extreme prostration. The picture of noma may develop, or the symptoms re- semble closely those of a malignant diphtheria. In these cases albuminuria is common; purpuric and polymorphous eruptions, and tender edematous patches may appear in the skin. Appendicitis, empyema, pseudorheumatism, arthritis, gastroen- teritis, endocarditis, pneumonia, or peritonitis may develop as a complication in the severe cases. 430 Some writers attempt to recognize several forms of Vincent's angina. As the differences are wholly those of extent and degree, it seems inadvisable to class these varieties as distinct types. Every pos- sible stage exists between them. The ulcerative stage is only the later stage of the membranous. While the constitutional symptoms may be slight or absent, the local condition may be more marked than in diphtheria. The more severe cases are likely to occur in weakly children following other acute infections. A subacute or chronic course of the infection is not infrequent. Such cases may run three weeks to three months or longer without healing of the lesions. These cases are especially dangerous in transmitting infection to others. Prognosis. — Usually good. The complications of the severe form are relatively infrequent, but ex- tension to the larynx and trachea is very dangerous. Noma and other of the serious complications may result fatally. The occurrence of chronic cases must be borne in mind, however, so that a time-limit for the disease cannot always be safely made. Diagnosis. — The only positive test is that of the culture tube. Smears from the base of the ulcer will reveal the presence of the fusiform bacillus either alone or in association with the spirilla or other organisms. Cultivation is necessary to exclude diphtheria and other infections. Many cases of suspected diphtheria are undoubtedly cases of Vin- cent's angina; but before assuming that any ulcero- membranous process of the tonsils or mouth is Vincent's angina, diphtheria must be excluded by cultivation, as the clinical picture and stained prep- arations are in themselves not conclusive. Chan- croid and syphilis must also be excluded by the history, other symptoms, Wassermann's reaction, demonstration of Spirochete pallida and chancroid organism. Treatment. — Local applications of tincture of iodine or methylene-blue powder have been used with good results. The base of the ulcer may be touched with Lugol's solution, or a ten per cent, solution of silver nitrate. A thirty-grain solution to one ounce of zinc sulphate is also recommended. Weaver and Tunnicliff advise the use of hydrogen peroxide. Mouth washes, such as Seder's solution and potassium chlorate, are also used. Orthoform in powder or tablet form is advised for relief from the pain. Rumpel and Gerber obtained prompt healing of the ulcer after the administration of salvarsan with no other treatment and in cases where syphilis was excluded. Yates used North's lactic acid' prep- aration in a chronic case of mastoiditis due to the fusiform bacillus and obtained prompt healing with disappearance of the organisms. Internal medica- tion is regarded by most writers as unnecessary, although some advise the administration to children of the tincture of chloride of iron in doses of three to five minims, combined with glycerin ami water, every three hours. Complications should receive appro- priate treatment as they arise. A. S. Warthin. Angioblast. — (From the Greek aj-fetov, a vessel, and /iXacrris, a sprout.) The word A ngioblast was proposed by His in 1900 to designate the embryonic l issue that gives rise to the blood-vessels and the blood. For a discussion of the origin and fate of this tissue see article Blocrd-vascular system, origin of. It. P. B. Angiokeratoma. — Synonyms: Kerato-angioma : Tel- angiectatic Wart; Mibelli's Disease. Definition. — An unusual chronic skin disease, chiefly met with on the hands and feet of those sub- REFERENCE HANDBOOK OF THE MEDICAL SCI] \< Angiokeratoma jecl to chilblains. II consists of single and grouped papular and nodular lesions of a reddish or purplish color, made up of epi- dermic hypertrophy covering dila- tation 01 ill" capillary vessels in the papilla?. History. Mibelli ga\ e the first anatomical description of I In- con- dition met with in the affection proposed the name "angio- keratoma" for the disease. The lesions n hich formed i he basis of his observations occurred on the il hi face of the fingers of a year-old girl, and had existed for several years. They preceded by chilblains. Before Mibelli's careful investi- gations, cases of the same affection hail been noted by other writers under various names; the true nature of the lesions had not, however, been determined. We are indebted to Pringle for a most accurate and painstaking description of the clinical appear- and morbid anatomy of the affection, as well as for an analysis of most of the cases which had been met with up to the time of his publication. Pringle reported two cases affect- ing girls with chilblains, and his histological findings agree in all essential points with those of iMibclli. Since the publication of these cases a number of others have been reported, among them Zeisler's, which presented, in ad- d^ 10 " 2J?.'T Se °? 0n throu e h Sm all Blood Cavity Completely Enclosed by Hypertrophied Kete. thickened epithelium at right of section. Spencer, one inch; ocular, one and onc- iiuarter inches. dition to characteristic lesions on the hands and feet, nevus-like patches and pedunculated vascu- lar tumors on the forearms, over the patellae, the legs, thighs, and auricles. In the case reported by myself, the skin of the scrotum was the seat of a number of small, spheri- cal-shaped, dark purple tumors. They were arranged in a linear manner as if following the super- ficial vascular supply of the parts. The small growths, from the size of a pin's head to several times that size, were distinctly elevated above the surface of the scrotum, seeming to rest on it rather than to be embedded in the skin. Some of them were covered by a slightly thickened horny layer under which minute dark red points could be seen, giving the tumors a wart- like appearance. In this patient the hands and feet were not in- volved, and the usual etiological factor, chilblains, could not, of course, be invoked to explain the development of the lesions. I have also, through the kindness of Dr. Leviseur, seen a similar case in which the small tumors were seated on the vulva of a young girl. The diagnosis, in this case, was confirmed by the micro- scope. Anderson has reported a case in which the eruption began over the 431 w " 41 ' — LarEe Tumor Showing Cavernous Spaces Divided by Fibrous Septa. Organized blood clots on the left of section. Spencer, one inch ; ocular, one and one-quarter inches. Angiokeratoma REFERENCE HANDBOOK OF THE MEDICAL SCIENCES knees at the age of eleven years, gradually spreading to the trunk and upper extremities, and finally involv- ing almost the entire surface of the body with the exception of the hands and feet. Symptomatology. — A history of recurring attacks of chilblains precedes the development of the affec- tion on the hands and feet. After a variable time, usually reckoned by years, minute telangiectases appear over the dorsal surfaces of the phalanges of the fingers and toes, which eventually cannot be made to disappear by pressure. The points of vas- cular dilatation become grouped, and over them the epidermis undergoes thickening, giving rise to hemis- pherical lesions from the size of a pin's head to that Fig. 242. — Cavernous Space Filled with Blood Corpuscles and Divided by Fibrous Septa. Hypertrophy of stratum comeum and rete Malpighii. Spencer, one-half inch; projection ocular, 2 Zeiss. of a spilt pea, or larger, having a rough warty surface and a dark purple or lead color. The minute vascular points beneath the thickened epithelium can be detected by making pressure on the growths. In some cases lesions in all stages of development from minute pink points to the commingled warty growths can be detected. The palms and soles may be involved. On parts of the body where the stra- tum corneum is thinner than on the hands and feet its hypertrophy is less marked than in the latter localities and may not be perceptibly thickened. It is usually bilateral, though not strictly symmetrical. The affection may persist indefinitely, become sta- tionary, or disappear. Patohology and Morbid Anatomy. — The primary change is undoubtedly in the capillary vessels of the papillae, which, subjected to repeated congestions, become permanently dilated, leading to the for- mation of cavernous spaces, and by pressure alter the normal conformation of the parts. On the hands and feet the stratum corneum covering the lesions is greatly thickened; this change is not so pronounced, however, when the affection is met with in other regions. The characteristic pathological changes are shown in the accompanying photomi- crographs made from sections of tumors removed from the scrotum. In Fig. 240 a small cavity filled with red and white blood corpuscles is shown completely surrounded by the hypertrophied rete layer. On the right of Fig. 241 a large cavernous space is seen to be filled with blood corpuscles, which have by pressure caused a marked atrophy of the epidermis. On the left of this section the circulation has been obliterated, as the lacuna? are occupied by concen- tric layers of fibrin containing blood corpuscles and pigment. Fig. 242 represents a more en- larged view of the cavernous spaces with their divided septa. The stratum corneum is also shown to be considerably thick- ened. An examination of the sections shows that the lesions consist of lacunar spaces filled with blood occupying the papillary portion of the derma, some of which are enclosed in the rete Malpighii. These cavernous spaces are evi- dently the essential feature of the disease and the primary patholog- ical condition. Etiology. — The disease, when it occurs on the hands and feet, as it most frequently does, is an affection of early life, and caused by repeated attacks of chilblains Some cases have been associated with tuberculous affections of the lungs, glands, and other regions. An attempt has been made by Leredde to show that it is caused by the toxins of the tubercle bacilli. It is hardly to be hoped that the von Pirquet reaction will decide this point. Scheuer, one of the most recent systematic writers on this affec- tion (1909), like many of his pre- decessors, regards it as due to an initial congenital weakness of the capillaries aggravated in most cases by frost-bite. The subse- quent thickening of the epidermis is conservative as it protects the fragile vessels and thereby pre- vents hemorrhages. In my case, in which the skin of the scrotum was affected, the tendency to dilatation of the blood- vessels as manifested by a double varicocele, and the degenerative state of the vessels and surrounding connective tissue incident to old age, 'were probably the most potent causes in bringing about the condition. Diagnosis. — A well-developed case of the disease could hardly be mistaken for any other affection. The color of the lesion and the presence of the vas- cular points should differentiate it from tuberculous or ordinary warts. Treatment. — The tumors may be removed bj excision or by (he application of the Paquelin or galvanocautery. with the production of slight scarring. Less deformity results from electrolysis. John A. Fohdtce. Literature. Mibelli: Giornale Italiano delle Mai. Ven. e della Pellc. fasc iii . September, 1SS9. Internat. Atlas of Rare Skin Diseases, No. ii., 1889. Dubreuilh: Ann. de la polyclinique de Bordeaux, tomei., fascio i., January, 1S89, p. 50. 432 REFERENCE HANDBOOK 01 THE MEDICAL SCIENCES Angioma Pringle: British Journal of Dermatology, vol. iii., 1891, p, 237, Zeislor: Trans. American Dermatol. Association, 9even I Motting, I s ' 1 ; Fordyce: Journ. Cutan. and Genito-Urin. Dis., vol. \i\.. LS96, p. 81 Vndorson: British Journal ol Dermatology, vol x., 1898, p. 113. \i.n. do Derm., 1S98, vol i\ . i> 10 Arch i Derm, u, Syph., L909, xoviii,, p. 251, Angioma. — (iyytiov, a vessel.) The angioma, a neoplasm representative of the connective-tissue or histoid type of tumors, is a new growth composed eal pari of blood-vessels or of lymph vessels. on.- According to the character of the sels entering into the structure of the tumor. angiomata are classified into — 1. Hemangiomata; _'. Lymphangiomata. Hemangioma. — The hemangioma is a tumor the atial structural components of which are newly formed blood-vessels which are formed from the preexisting ones by budding. The older \< may also grow lengthwise, and become tortuous and dilated. Varieties. — Two varieties of hemangioma are rec ognued, the distinction between them being ba upon differences both in structure and in location. These varieties are: Hemangioma Simplex (nevus vasculosis; birth mark; telangiectatic hemangioma). This form of hemangioma comprises the small vascular nevi, and most of the so-called mother's or birth marks, it occurs in two forms: (1) As flat, round, or irregularly outlined, usually sharply contoured, red or bluish-red patches on a level with, or but very slightly elevated above, the surface of the skin; in size, varying from that of a flea-bite to that of the side of the face. The skin over these patches is either smooth or thickem I. and is sometimes covered with lanugo hairs. (2) As telangiectatic warts, from pin-head to pea size, which appear in the elderly. The blood found in them is venous in quality. They do not really originate in old age, but become conspicuous at this time. The blood-vessels running to and from the wart suggest the appearance of a spider — the "spider cancer" of er quacks. currence. — This variety of hemangioma is very common; it is nearly always congenital. From observations made by Depaul, it appears that one- third of all the children born in the clinic of the Fac- ulty of Medicine in Paris have such hemangiomata at birth. The tumor is situated most frequently in the skin of the face, neck, back, chest, abdomen, sometimes of the extremities. More rarely it occurs in mucous membranes, and beneath the serous sur- s of the internal organs. It may be single or multiple, and may attain a varying size. Structure. — Histologically, the hemangioma simplex consists of newly formed, much convoluted, more or dilated capillaries lying in a stroma composed of fibrous connective tissue or of fat tissue. This stroma varies in amount, and may be infiltrated with lymphoid cells, or contain pigmented connective- tissue cells. The newly formed vessels often corre- spond in distribution to the vascular districts of the sweat-glands or the hair-follicles. The vessels com- municate not at all or but slightly with the normal blood-vessels. Hi mangioma Cavernosum (cavernous tumor; erec- tile tumor; cavernoma). — This form of hemangioma isists of lobulated, sometimes fungoid tumors of varyjng size, bluish in color, single or multiple, tending diminish or disappear under pressure. Pressure upon parts adjacent to the tumor causes it to swell by venous congestion; other conditions, such as change of position, weeping, sleep, digestion, the ingestion of alcohol, and the like, may cause alteration in size, owing to the erectile character of the growth. Vol. I.— 2S Occurrenci rhe ordinary M-its of this tumor are the lips, check-, tongue, and muscles in general. In exposed localities they cause much disfigurement. A special form is cavernoma of the liver, The size \ anea from that of a pea to t hat of a whole lobe of the liver, The tumor i.s general!} single, sometimes multiple. The liver of old i pie pn enl this form of new growth in a great number of instances. Its occurrence In this organ seems to vary in frequency in different countries; according to the report of patholo- gists, it is not so frequent in Norway and Swei as it is in Germany. By the rupture of the vessels of large cavernous hemangiomata through the capsule of the liver, extensive hemorrhage has taken place int.. the peritoneal cavity, and fatal peritonitis has been caused. Fig. 243.-— Angioma Cavernosum Cutaneum Congenitum Muller's fluid; hematoxylin.) a, Epidermis: b, coriumjc, cavernous blood spaces. X20 diameters. (After Ziegler.) This tumor also occurs, although less commonly than in tin 1 liver, in the other abdominal organs, as, for example, the spleen and the kidneys, and also in the brain. It is found in the skin less frequently than are the simple hemangiomata. Esmarch has re- ported in Virchow's Archiv a very interesting case of its occurrence in this position. A single tumor devel- oped upon the middle finger of a girl eight years of age was followed in subsequent years by t lie appearance of a great many others. At the time of the first menstrua- tion there was a great increase in both the number and the size of the tumors. At each succeeding cat- amenial period they seemed to grow more than at any other time. In size they varied from that of a pea to that of a hen's egg. They- were all successfully extirpated, and in most cases were found to be situ- ated on the wall of a vein, with which they were in communication. Structure. — The cavernous hemangioma upon sec- tion presents an appearance quite similar to that of the cut surface of the corpus cavernosum penis. It is characterized by the presence of a firm, tough, white meshwork, which in the recent state is empty or contains some irregular blood clots. The meshes frequently enclose small, round, calcareous masses known as phleboliths. In some instances this cavern- ous structure is sharply circumscribed and separated from the surrounding structures by a firm capsule. In others, where the tumor is small and to all appear- ances in a state of rapid growth, it is surrounded by a zone of h/mphoid cells. The consistence of the tu- mor depends upon the amount of the fibrous connec- tive-tissue meshwork, or stroma: when this is abun- dant, the tumor is relatively hard, and when scanty, soft and flaccid. Microscopically-, the tumor presents trabecules of fibrous connective tissue, in part newly formed, in part belonging to the structure in which the tumor is developed, of varying thickness, arranged in the form of a meshwork. The cells of this tissue are numerous, and it is usually infiltrated with lymphoid cells scat- tered singly or localized in groups. The spaces of this meshwork are lined with flat endothelial cells, and contain blood. These spaces are of varying size, but whatever their extent, they always represent capil- laries, for they are interposed between an artery- and a 433 Angioma REFERENCE HANDBOOK OF THE MEDICAL SCIENCES vein. Adjacent large spaces may be separated by exceedingly thin partitions. The connective-tissue stroma in some cases has been ,found to contain nerves, smooth muscle fibers, and elastic fibers. Ribbert has shown abundantly by injection experi- ments that the blood-vessels of the tumors do not communicate with the general circulation in the great majority of cases. Etiology. — The cause of hemangiomata, in common with that of most new growths, is not understood. A large proportion of all tumors of this sort are con- genital, and when they do develop after birth, it is generally in the early years of life. It is seldom that hemangiomata develop in adults, a fact which is remarkable in view of the frequency of dilatation of the blood-vessels in old age, and one which constitutes Fig. 244. — Dilated Capillaries from a Telangiectatic Tumor of the Brain, all the attached portions of tumor tissue having been shaken off in water. X200. (After Ziegler.) a strong objection to the theory that these tumors arise from a simple dilatation of preexisting vessels. Heredity seems to play some part in their occurrence; numerous cases are recorded in which a child presented one of these tumors in the same place on its body as that in which one of the parents also had a birth mark. Popular belief in all ages has associated the presence of these growths in children with some influ- ence exerted upon the mother during pregnancy; maternal impressions cannot, however, be regarded as definite factors in the development and growth of offspring. Different views have been held regarding the genesis of the cavernous form of hemangioma and the most distinguished pathologists have promulgated positive views on the subject. The cavernoma of the liver is well suited for study. Ribbert regards it as the result of an error of development, an area of embryonal liver tissue being involved with its imma- ture cells, trabecules, and vessels. The vessels develop at the expense of the other structures. They become irregular and dilated. This, however, does not explain the tumor formation, which develops on the basis of the malformation and is brought about by the appearance of buds in the walls of the sinuses. These force their way between the liver cells in the direction of the capillaries. In this way large tumors are formed. A cavernoma then begins by dilatation of embryonal vessels into sinuses and extends by the continued formation of new vessels. In some cases the growth undergoes a fibrous transformation, the connective tissue increasing at the expense of the blood-vessels. Mmlc of Growth; Clinical Aspects. — The hemangio- mata extend always by growth from within outward- they show no tendency to infiltrate surrounding strut tures; they do not cause metastases. Instances of seeming exception to these conditions are probably cases in which sarcoma with dilated blood-vessels was mistaken for hemangioma. The pulsating tu- mors of the long bones, whioti have been described as cavernous tumors, are to be regarded as telangiei tic sarcomata. The hemangioma is, therefore, si i as its mode of growth is concerned, a benigti tumor although the accidents incidental to its development may cause death from hemorrhage or from intra- cranial pressure. The growth of these tumors is generally unaccompanied by pain; it is slow, ami may be irregular. In some instances the tumor constantly enlarges, in others it reaches a certain size and then remains stationary. It sometimes under- goes spontaneous cure by the ulceration of the overly- ing skin, and the subsequent formation of cicatricial tissue which includes the vessels and obliterates them by contraction. When, as is sometimes the case. I ! tumor is connected with the skin by a pedicle, I lie vessels in the pedicle may shrink, and the tumor become desiccated and drop off. In yet other ca a cure may be effected by thrombosis, and the con- sequent deprivation of the tumor of its circulation. Lymphangioma. — The lymphangioma is a tumor composed of lymph vessels and lymph spaces in a state of greater or iess degree of dilatation, lying within a fibrous connective-tissue stroma. Strictly speaking, the term lymphangioma is applicable to those lymph- vessel tumors only in which the whole or the greater part of the vessels is newly formed; but inasmuch be in any single case it is often difficult to determine how far the vessels are newly formed and how far they are preexistent, dilated and thickened, it is con- venient to include under the lymphangiomata certain abnormal structures in which the essential patholog- ical condition is lymphangiectasis. This form of new growth occurs in a great variety of loci, and pre- sents an external configuration determined very largely by the organ or structure in which it is de- veloped, as well as by its histological characteristics. It is seen in warty tumors and diffuse thickenings of the skin and mucous membranes, in macroglossia, in certain congenital cysts, and in various other conditions. Fio. 245. — Section through the Margin of a Very Small Cavernous Angioma of the Liver at a Time When This Mi Was in Process of Active Growth. (Carmine preparation.) X 150 diameters. (After Ziegler.) These growths may be classified as follows: Lymphangioma Simplex. — Asa true neoplasm this oc- curs in the form of a circumscribed tumor, composed of capillary and larger-sized lymph vessels. As lymph- angiectasis, it is seen in the lymphatic varix, in dilata- 1 i< hi of the lymphatics resulting from obstruction, in macroglossia and elephantiasis following erysipelas, and in elephantiasis due to filaria. There are numer- 434 REFERENCE HANDBOOK OK THE MEDICAL SCIENCES Lngloma Serplglnoguni . dinical forma of lymphangiectasia, congenital I acquired, bul Ribbert does not regard these as angiomata, neither does he include here l\ inph- . u ,„i atuberosum multiplex.a very rare skin di ea e. lymphangioma Cysticum. — Some authors distin- D betwei n cavernousand cysticforms, bul Ribberl mllk , . oa b olute distinction for cystic and cavernous tumors occur side by side. . growths are practically isolated, their ve el having little or no communication with the normal lymphatics. \ true lymphangioma should shell out ,,,,, the surrounding tissues. The size may thai of an apple or the list. e is, however, a lymphangioma cayernosum i i ricted sense « hich i urs as a diffuse ,: , embling in structure a hemangioma, h ig congenital, and occurs in the lips, cheeks, and tongue, causing an elephantiasis known respectively tc'rocheilia, macroglossia, etc. j I - .•9'n».'" , .-- ! Flo. 246.- Lymphangioma Hypertrophieum. Rounded summit of :i rather large, .soft, smooth wart. (Formalin; hematoxylin; Sharply limited nests of cells in the corium. X250 diameters. [After Ziegler.) These lymphangiomata occur in various parts of the body with especial preference for the axillae, groins, mesentery, and intestinal wall. An atypical, ill-defined form occurs in various localities about the neck and is known as congenital cystic hygroma, li may reach as high up as the ear, may extend down- ward into the mediastinum or hang loose upon the neck or shoulder. The cystic lymphangioma of the neck is congenital; it is probably not derived from hemangioma by the obliteration of connections with blood-vessels and the development of secondary communications with the lymphatic system. The fact that the cystic spaces are a with endothelium and not with epithelium is evidence that these, tumors are not derived from i- the salivary glands or the branchial clefts. I'he tumor is situated upon the anterior or lateral surfaces of the neck; rarely upon the back; it may be unilateral or bilateral. Its size varies; it tends to burrow and to extend under the cervical fascia between the muscles of the neck. In this way it may travel down the sheath of the subclavian vessels to the axilla, or it may go into the mediastinum. Sh'uctiirc and Nature. — Lymphangiectases, like telangiectases, are not to be regarded as tumors. Lymphangioma proper agrees in structure and nature with hemangioma. That is, there i lii i m ei i "i ni de\ 'In | 'Hi, which re nil in a new foi i em ..i ves els and connective tissue, together with fat and smooth muscle. In the simpli ' form there new formation and dilatation 01 lymph vessels and spaces. There is a tendency, however, to multiple cyst formation, the cysts as a rule having communica- tion with one another. \ sect! f such a growth ihows a mass of cavernous tissue with cavities of various size, including perhaps one largi ' ■ ity. The dilatati E the lymph spaces to form cysl i not due in the main to distention and wearing away of trabecular, but to a true process of growth which constantly increase the internal surface. As the spaces thus enlarge, they keep filled with lymph. ( 111, i.i. I 'ii i.i, M LGRA1 II. Edward Pbeble. Bibliography. Beneke: Zur Genese der Leberang Virch. Archiv, 1S53. Burckhard: Path, Uiat. d, oavernoesen Ang. d. Leber, Wurz- burg, I. !>.. 1894. Esmarch: I ebei cavernoese BlutgeschwOlste. Virch. Arch., 1853. II. rtzler: Treatise on Tumors, 1912. Lang] Beitrage Lehre iron den Gefat sgei chwulsten. \ irch \ich.. 1879. Losser: Lymphangioma tuberosum multiplex. Virch. Arch., 1891. Logez: Le Lpmphangiome congenital. These de Paris, 1902 Luschka: Cavern. BlutgeschwOlste des Gehirns. Virch. Arch., 1854. Muscatello: Angiom der willkOrl. Muskeln. Virch. Arch., 1894. Ribbert: Geschwulstlehre, 1904. Robin ei Laredde; Arch, de med. rap. et d'anat. path., 1896. Rokitansky; Lehrbuch d. path, Anat., 1855. Samte: Ueber Lymphangiome d. Mundhohle. Lang. Arch., 1891. Sutton: Tumors, Innocent ami Malignant 5th. ed., 1911. Virchow: Ueber cavern. Geschwulste. Virch. Arch., 1S54. Virchow: Hygroma cysticum glutcale congen. Virch. Arch. 102. Virchow: Die krankhaften Geschwiilste, 1SG3. Wegner: Lang. Arch., x\. Weil: Beitriige Zur. Keuntniss der Angiome, Prag, 1877 Angioma Serpiginosum. — This rare cutaneous dis- order was first described by Mr. Jonathan Hutchinson, in his "Archives of Surgery," in 1891, under the title of infective angioma or nevus lupus. Crocker's name, angioma serpiginosum, would seem to be on all accounts the more appropiate. But a handful of cases, six or seven in all, have been reported, and it may be doubted if one or two of these are reallyentitled to a place in this group Hutchinson has also pub- lished a short account of three other cases, those of Lassar, Tay, and .lamieson. Besides White's case one other, incompletely reported, has been described in America, and Leslie Roberts refers to a case that may belong in this category, although differing from I he type in many respects. Schamberg has described a peculiar progressive pigmentary disease that offers certain resemblances with angioma serpiginosum. In all the cases thus far reported the affect ion began in early life, in four of them before the age of two years. Small bright red papules; firmly seated in the skin, are the first manifestations. These papules do not dis- appear on pressure, and have been likened to Cayenne pepper grains. They increase in size slowly, and may reach the size of a pea, when central involution occurs, while the edges continue to spread so that circinate figures are produced. Outside these circles, small new lesions, called satellites by Hutchinson, are continually making their appearance, which also enlarge and undergo central involution so that new rings are formed, which may unite with the original ones. There is no apparent atrophy in the central part that has undergone involution, but in White's case there was a dull pigmentation in this portion. In none of the cases thus far reported has there been any breaking down or ulceration of the papules. 435 Angioma Serpieinosum REFERENCE HANDBOOK OF THE MEDICAL SCIENCES In Hutchinson's cases the lesions were situated on the back of the arm, spreading upward to the shoulder and downward below the elbow. In the other cases, the arm and side of the thorax, the face and upper extremity, and the lower extremity, have been the portions affected. White's case, which was seen and studied by the writer, concerned a boy of twelve years, who had always been delicate and of a very nervous tempera- ment. At birth a semilunar red mark was noticed below the right shoulder blade, which increased very slowly in an upward direction until he was four years old, when another spot the size of a pin's head made its appearance near the first one, which gradually grew larger, and since then other spots have continu- ally appeared and grown larger. When the patient was first seen, the affection formed a band three inches wide, which extended from the anterior edge of the right scapula, about six inches forward toward the nipple, and was composed of about twenty-four different lesions, which varied in size from a pin's head to circular patches more than two inches in diameter. Minute elevated points, of a bright red color, first made their appearance, which increased slowly in size until they were from one-eighth to one- twelfth of an inch in diameter. They were of firm consistence, and only partially disappeared under long pressure. Involution in the center then began, while the growth spread peripherally, so that circles were produced, until by confluence with other lesions near by this shape was lost. The skin in the center of the lesions appeared normal except for the presence of a distinct pigmentation. New lesions were continually appearing at a little distance from the older areas, and in one or two instances small foci were apparent in the old central portions. The anterior group of lesions, some seven or eight in number, were at one time destroyed by the Paquelin cautery. Pale cicatri- cial tissue was formed at the site of the cauterization, and it looked as if the operation was successful, but after a time the lesions appeared on the borders of these scars, and the original condition was produced. In this case there was the greatest sensitiveness to slight pressure upon the affected region, but it is not improbable that this was due to the extreme nervous- ness and fear of the patient. There was also some itching complained of. The only careful histological examination that has been made of this remarkable disorder was that of White's case. A typical lesion was excised and one- half was studied by Darier of the St. Louis Hospital, Paris, and the other half by Councilman and the writer. Microscopically, the epidermis and the epithelial appendages of the skin, such as the hair follicles and sweat glands, were unaltered. The lesion was characterized by groups of cells throughout the corium, which were fairly well circumscribed, and ran in their general arrangement parallel to the surface of the skin. They were sometimes round, but more often elongated in shape, and sometimes extended out in long ribbon-like masses, which seemed to be formed by a coalescence of neighboring groups. The papillary layer of the corium was only here and there invaded by the process. Under a high power the nuclei were seen to be oval in form with a general direction parallel to the course of the mass. They were surrounded by a small amount of protoplasm, and the boundaries of the individual cells could not always be distinctly made out. The cells of all the groups were arranged in smaller groups or clumps, concentric in form, and in the center a lumen could sometimes be seen, showing their connection with the vessels of the skin. There were also various changes in the vessels, consisting in a swelling and proliferation of both endothelial and perithelia! cells. A striking feature was the presence of small granular masses here and there in the cell groups, which showed no definite structure, and which were evidently produced by a degeneration of the cells, as there was every gradation from slightly granular, poorly staining cells to a total necrosis. In some places the cell groups were situated about spaces and fissures which evi- dently corresponded to lymphatics. Taken as a whole, the process is evidently one connected with the vessels of the skin, affecting certain groups of vessels notably the blood-vessels. It seems to begin by a' proliferation of the endothelium of the vessels accom- panied also by a proliferation of the perithelium which is followed later by a degeneration and necrosis of the central cells. There is apparently no com] new formation of blood-vessels. Histologically, the growth is to be compared to an angiosarcoma, and its cause is possibly that underlying tumor formation in general, and due to some congenital condition of the vessels. Darier, from his investigations of the case in question, proposes the name Sareome angioplas- tique reticule. He considers that we have to do with a peculiar form of sarcoma which is not massed to form a single tumor, but has a reticulated structure following the vessels of the skin, and that there i- a tendency to form clusters of capillaries, approaching in this way the characteristics of a true angioma. He refers to the fact that in some of the soft nevi cell forms are found very similar to those of this ca i The number of reported cases of this disease small to warrant any general conclusions as to its course. In Hutchinson's case there was a recurrence of the growth after cauterization. In White's case the nodular infiltration made its appearance in the normal skin beyond the scar left from cauterization. This patient was seen six years later, when he had reached the age of eighteen. There had been some treatment by cauterization in the meantime, and again the appearance of lesions jumping over the part treated, to reappear beyond the cicatrix in the sound tissue, was seen. There had been no breaking dowa in any part, and on the whole it seemed as if the proc- ess was gradually becoming less active. When last seen, several years later, the process had undergone still further involution. Treatment of this affection has thus far proved most unsatisfactory. Caustics or excision may con- vert the territory occupied by the lesions into a cica- trix, but hitherto they have failed to stop the peripheral spread of the disorder, and sometimes new lesions have recurred in the scar tissue itself. Elec- trolysis applied along the edges that are progressim; has been advocated, but no successful results from this or any other method of destruction have been reported. John T. Bowen. Angioneurotic Edema. — This condition is better described as acute circumscribed edema [Quincke], since such a name makes no attempt to explain the phenomena on the basis of a hypothetical vascular neurosis. The more striking skin edemas were described as early as 1778 by Salpertus. Erichton in 1801 also observed them, and Graves, who gave such an excel- lent outline of exophthalmic goiter in 184S described a patient with localized swelling of the face, forehead, and eyes, in whom the edema persisted only a few hours. Various aberrant localizations have bei n reported, often under different names. Naturally hysteria bulked large in the diagnosis in the earlier days. Other synonyms indicate under what dif- ferent rubrics it was grouped: Urticaria, urticaria redematosa, urticaria tuberosa, giant urticaria, all indicate where one should search the early literature, further, one finds rheumatic edema, arthritic edema, repeating rheumatic edema, intermittent rheumatic edema, neuroarthritic edema, in the period when the cases would be grouped among the rheumatisms, etc. Then again, under the influence of the edema concept, we find wandering edema, non-inflamma- 436 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Angioneurotic Edema tory edema, transient swellings, local transien< na intermittent edema, etc, etc. Quincke ISS2 described it as acute circumscribed skin edema, , | u -[ e i n a Kiel dissertation, one of his students, Dinkelacker, broughl together many of the older de- scriptions in I showed the unity of several apparently dissimilar pr . He termed it acute edema. Since Quincke's time a large bibliography has accumulated, must of which is to be found in Cassi- \ i omotorisch-trophischen Ne q, second dition, 1912. A few of the papers in English are Bannister, Journal of .Vervi ' 1894; Bramwcll, Clinical Studies, 1907; i f the Mt dical - 1892 Kohn, I U ■ , 1901; Medicine. OCCURRENCE. — The disorder is not frequent, yel nol rare. Men and women appear about equally nvolved. It may be present in young children— i one-half months, Crozier, Griffith; three months, Dinkelacker. Alter forty it appears very •arely as an initial development, although in affected ndividuals it may persist until late in life. Cas .-,.,1 cases in persons oi seventy-nine and sixty- urs in which the disease appeared compara- ite in life. Raven reports a case in a woman ighty-six. Etiology. — Occupation apparently plays no role. idity on the other hand is conspicuous. Many luthors have mentioned this feature. Osier's family ; been freely cited. Ensor reports a family if eighty members with thirty-three aff' ndividuals, twelve of whom died of edema of the glottis. - nilar hereditary features an? reported by sev- ral observers. The question of its transmission been completely cleared up. In Apert and Delille's families only the males were affected, but :his does not seem to be the rule. In many families, similar types of localized edema ail in the members, while in others, apparently nore often, all of the possible variants disappear. ; I ervous system involvements appear associated n many of the families: how much of this is largely ^incidence, how much general neuropathic causal bionship is difficult to determine from the studies it hand. Much depends on the point of view of the ndividual, whether he sees a relationship of the s with those of epilepsy, migraine, chorea, gout, manic depressive insanity, paresis, etc., all of which lave been swept into the hereditary net. Some fami- show no heredity factors of any recognizable kind. In the search for etiological factors, much industry been evidenced, and the disease has been reported having either direct or concomitant relationship with acute articular rheumatism, alcohol poisoning, ■arbon monoxide poisoning, tobacco poisoning, ating of fish, oysters, and mushrooms, and malaria. ll has been found very frequently in certain places in Lower Sehleswig where Lowenheim has reported HO cases in the neighborhood of Liegnitz. No family tree search was made, and this author is in-lined to make certain climatic factors respon- sible — damp swampy localities, with the heat of July and August. Eschweider has reported its frequent irrenee in Diisseldorf prison where certain pas- tilles were made. The disease infrequently shows itself in relation to organic nervous diseases — tabes, myasthenia gravis, spinal cord tumor, exophthalmic goiter, myx- na, paraplegia — while it seems very frequently iciated with many so-called functional neuro- pathic states — hysteria, neurasthenia, tics, compul- sion neuroses, migraine, etc. — and in certain psy- chotic individuals with schizophrenia, manic depres- sive psychosis, idiocy, amentia, etc. Local traumata play a rule at limes, particularly in determining the location of the swelling. Emo- tional shock seems to bulk large aa a direct etiological in tor, as does also the action of thermal influei i Cold is very frequently an exciting factor in the reaction. Menstrual facto) eem to enter into the i iology of certain cases. A moment's reflection therefore will show that under the term Acute Circumscribed Edema one is dealing with phenomena of greal variability and multiform pathogeny. In discussing the patholo a return will be made to this many Bided etiology. Symptomatology. — The original conception of Quincke lias been much employed, and Cassirer in his Large monograph shows the present day trend to include a large number oi is o sweUings within tin cal group. Thus one distingui localized edema of the skin, edemas of the mucous ol thi eyelids, mouth, glottis, esophagus, stomach, i respiratory tract: i the joints, of the tendinous aponeuroses, possibly of the kidneys, with polyuria, albuminuria, hemoglobinu- ria, diminished secretions, etc. The onset is usually acute, with some initial pro- dromal signs of malaise, fatigue, chilliness, anorexia, nausea, and slight rise in temperature. A . This is localized, variable in size, at times small, resembling urticarial blotches (intermediary forms but usually as distinct swellings, with an elastic feel, and due to a local accumulation of clear colored serum within the skin. The color of the swelling is usually that of the skin, or paler, rarely red or reddish. The swelling comes on with great rapidity, a few moments only, and remains a few hours, mostly a few days, and then disappears without leaving any trace. It is as a rule non-irritating, painless, and causes only a dis- comfort due to tension. Certain cases show burning, itching, and intense pain. The size of the edematous patches varies greatly. At times very small — one-half inch — they- are more apt to be three to four inches in diameter, or at times involve the larger part of a limb. The scrotum may at times swell up to the size of a foot-ball. The penis, in cases reported by Bonier, has swollen to double its diameter. The entire body was swollen also in a remarkable case reported by Diethelm. At times swellings are numerous, polymorphous, semi- confluent. They rarely rise more than one-fourth to one-half centimeter, but two to four inch swellings above the skin are reported. The margins of the sw-ellings are usually sharply circumscribed, but at times may shade off imperceptibly into normal anas. Circular or sausage shaped are the usual descriptions of the swellings. The swellings invade almost any layer in the skin, or musculature or even appear periosteal. Some have been termed pseudo- lipomas. The consistency is semi-hard, non-pitting, or slightly so. The color as stated is usually that of the normal skin, or it may/ be paler, or have a cadaveric hue. Again it is pinkish, to red, or even deep red. Often the color disappears on pressure. The color may change during the rise of all the swelling. Local temperature varies. At times the skin is colder, again it is warmer than that of the non- affected parts. Exact studies are wanting. It seems not unlikely that there is an initial increase in the local temperature. S< nsory changes are not present as a rule. Certain cases have shown preliminary neuralgic twinges, no perceptive sensory defect has been noted, but refined methods of examination, such as those demanded by Head, have not y r et been made. There is fre- quently the subjective sense of great discomfort, especially in marked swellings about the face. There are rarely any residuals, although occasion- 437 Angioneurotic Edema ally scaling or peeling has been observed, probably for the more superficially lying edemas. Si cretory symptoms have not been carefully recorded. Local hyperhidrosis, dermatographia, increased tear secretion have been noted. • The location of the swelling may be almost any- where, it cannot be said that one place more than another is a favorite site (statistically). Exposed portions of the body seem to be more often involved, but when it is on the hands or arms, the distribution is not of the glove type, nor are the swellings apt to be symmetrical, nor docs there seem to be any radicular or spinal distribution. There is a distinct tendency for a recurrence of the edema to occupy a position involved during a former attack. Periarticular swelling constitutes a peculiar type, so do also parotid and salivary gland edemas. The mucous membranes are frequently involved The lips, mouth, soft palate, tongue, pharyngeal pillars, nasal membrane, larynx are all sites of election. The last is particularly frequent and dangerous to life. In these cases, other structures than the larynx are implicated, especially the epi- glottis and closely associated structures. In the larynx the mucous membrane is swollen and tense; the edema infiltrates throughout. When the larynx is involved, the symptoms are apt to be very marked. There is beginning tickling, with rapidly oncoming difficulty in breathing, until marked dyspnea may supervene, with death, unless intubation or tracheotomy is performed. Some ot these patients die within a few hours. Many cases, on the other hand, clear up in an hour, after severe dyspneic symptoms. . Edemas within the bronchi occur in perhaps twenty per cent, of the cases. They make up a certain percentage of the cases of asthma. Certain hay fevers possibly belong in this group. Lung edemas have been described. In edemas of the walls of the stomach, external signs are also usually present. There may be inter- mittent vomiting, or sudden acute pains, anorexia. The attack may last a few hours with severe pain, and more or less continuous vomiting finally ot clear or bile colored watery masses, marked thirst, and gradual disappearance of all of the symptoms. Bits of gastric mucosa have been accidentally dislodged which showed marked edematous swelling. In intestinal localizations profuse diarrheas are present, with colicky pains, meteorismus, tenderness of the abdomen, diminished urination, great thirst, and collapse. The diarrheas are purely _ nervous diarrheas, so called, and occur in association with other signs of a circumscribed edema. Rarer localizations present in the tendons have been described, particularly by Schlesinger. Muscle edemas are also rarely described, although it is prob- able that they are of frequent occurrence. Articular edemas have been mentioned. Optic-nerve edema is one of the rarer localizations, as is also an edema in the labyrinth leading^ to a Meniere syndrome. Acute conjunctival edema is not infrequent. The bladder, kidney, and heart structures are among the rarest localizations. Meningitis serosa, aphasia, are among some of the more problematical occurrences reported. Prognosis. — In general this is not good, lhe tendency to laryngeal localization must always be viewed 'with gravity. A great many individuals have died from edema of the glottis. Remissions are to be expected. Some patients suffer many years, others, but the minority it would appear, have but few attacks. There is some general tendency for the disorder to become milder as the affected indi- vidual grows older. Transition forma are common, especially urticana- like eruptions. Acroparesthesias, Raynaud-like at- 438 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tacks, local asphyxias of the extremities, paroxysmal hemoglobinuria, acroasphyxia chronica, erythro- melalgia, epidermolysis bullosa hereditaria, herpes zoster are all affections with which attacks have been combined, singly or in groups of two or three. Occasionally edema, acroparesthesia, and erythro- melalgia may alternate in one and the same patient. Pathogenesis. — Our conceptions concerning edema are undergoing such vital modifications that it is ■ practically impossible to interpret the findings here outlined along those present day lines that regard all e lemas as cell phenomena and independent of the mechanical conceptions of stasis, pressure, osmotic tension of the vascular and lymph vessels, etc., etc. In view of these studies in edema it is certain that we may look in an entirely different direction than vascular changes to account for this series of phenom- ena. The term angioneurosis will then be not at all applicable to this disorder. Whether the studies of Fischer and others in edema can be brought line here remains to be seen. At all events the sir statement of this being an angioneurosis cai weight than formerly, and one is tempted to look- further I'm- a more adequate explanation. The study of anaphylactic phenomena, especially as seen in the so-called anaphylactic serum reactiOl or serum diseases, has offered suggestive glimpses indicating certain analogies with the series of chai here outlined. We cannot go into these in any detail. It can only be stated that precisely similar proce e and appearances are found in the serum reactions, and that it is not without profit to inquire more into the mechanism of their production in an attempt to understand acute circumscribed edema. Unfortu- nately the mechanisms of the changes in the anaphy- lactic reactions are still much in the dark. One of the disconcerting features of acute circum- scribed edema, whether one views it in the light of a modified colloid absorption reaction, due to ti influences brought to the cells of the deeper layers of skin, muscle, or mucous membrane, or whether one views it as a modified neural reaction passing through intermediaries of the vasomotor system, which in their turn control, in some unknown way reciprocal tension relations, or chemical composition relations, is the total irrelevancy of the whole process either to vascular or to neural distributions. This makes it all the in. .re probable that there are a whole series of things in so-called acute circumscribed edema. It is no unicum, and analysis will show that a number of different pathological processes may underlie precisely similar skin phenomena. Cassirer adopts this view point, but consents to make only two groups of cases— (a) a toxic ante- toxic group, in which the poison works in some mys- terious way, which a wealth of language can conceal, better than it can reveal, and (b) a heredofamilial m constitutional neuropathic group, which he regains as intimately associated with instability in certain parts of the sympathetic or vegetative nervous sys- tem. This may be, he says, associated in some manner with modifications in the internal gli secretions. Here we enter another dark portal, .u all events, Cassirer is loth to permit so-called angio- neurotic edema to wander from the neurological told, and concludes that the disease is conditioned— M least his group (&)— by the lability of the sympathetic nervous system. Treatment.— This is purely empirical. It con- sists first in avoiding all those things which experi- ence has shown to be liable to bring on an attack. If one has one of the more pronounced tOMC- anaphvlaxis-like reacting types, careful study must be made of all of the patient's protein reactions, and attempts made calculated to eliminate such from J diet. It seems plausible that it is through the gas- trointestinal canal that such products gain entry, REFERENCE HANDBOOK OF THE MEDICAL SCIENI ES Anldro-ls particularly in food, yet some may enter the respira- tory tract. as seems to be the case in the related hay- r reactions which are known to follow certain tacts, variously ascribed to ragweed, rose, hay, r poll, -us, or even the emanations from cattle. From specific exclusion of certain protein . the general hygiene of the intestine. This means a sort of search in the 'lark 10] mysterious ncies by chemical magic. One is justified not- withstanding in trying to bring about altered bowel liich empirically may do some good, when a laissez-faire attitude seems to perpetuate the disturbance. Naturally one should avoid cloaca! ihould the patient be of an entirely different type, say, the intensely neurotic forms with ilial hereditary burdens, and emotional shock lions. Of the gastrointestinal antiseptics so called, few are such. .Menthol, saline laxatives, carbonated careful dieting (?) may be found among the eatises on the subject. The taking of a milk-vegetable diet has been coincident with better- t in some individuals and coincident with retro- sion in othi In certain cases with associated toxemias, such as -.. a specific therapy is indicated. On the supposition that the bloi needed ing up to prevent transudation through their walls, also a hypothetical postulate, apparently ii quate, such drugs as strychnine, ergot, arsenic, atro- pine, morphine have been recommended. While all of these will bring about vasoconstriction it is not apparent whether they can alter a hypothetical tran- quility or not. Calcium lactate is the modern weapon for this latter. The writer has not seen it i but it may be of service in preventing transudates, as such are thought to be conditioned by a diminution in the calcium content of the body plasma Cassirer mentions calcium chlorate. At all events the vasoconstricting drugs have not been of any particular service clinically. Xow and then they seem of service; none has been proven of pro- phylactic value, which is a stricter test of their use- fulness, since the disease is so self-limited. In those ca mted with laryngeal symptoms, intubation is often necessary — even tracheotomy. There are records of certain patients condemned to the persistent tracheotomy tube. In the more strictly neurotic type — Cassirer's group (6) — it is highly important that they be taught a healthy morale. The substitution of reasonable and intelligent actions for purely instinctive and emotional reactions must be acquired by them if they can hope in any way to control their hair-trigger sympathetic nervous system. Perhaps it was so given to them, defective and badly coordinated; even then a rational pedagogy will prove of service. Many will be helped by the methods outlined by Dubois or Dejerine; others will need a psychoanalysis. Steckel has reported some extremely interesting and severe asthmatic cases, with pronounced symptoms of cir- cumscribed edemas with psychoneurotic combina- tions or complications. Just how the psychical pathways become involved in these complex neuro- biochemieal relations is one of the unresolved anatomical problems. Physiologically it is known that they do, as Pavlov's dogs nave demonstrated, and as even the man in the street knows through the profound disturbance of his bodily functions which may be brought about by emotional states having perhaps only mental representations, memories, as their foundation. Smith Ely Jellifie. Angiostomidse. — A family of nematode worms which manifest in development the alternation of two types of sexual generations, of which the first is free and dioecious, while the second is parasitic, of different structure and hermaphroditic. The genus Strongylaidea is found in the intestine of man. oda. A S P Anguillula. — A genus of nematode worms. A. aceti lives in vinegar and paste; tin has occasionally b. i in the urine of man oda. A S. P. Anguillulidc-e. — A family of mi orms, for the most part small and free living. The esophagus usually ha- a double swelling, or two "bulbs." Many es live in humus or decaying matter, other- live on or in plant-: some, such :: I /.; aceti, \ in vinegar, paste, and urine, live inorganic fluids. See A> matoda. A s. P. Angustura. — See Cusparia. Anhalonium.— See Mescal Buttons. Anidrosis. — Anidrosis in the usual meaning of the term denotes a disturbance of the function of the piratory glands in which their secretion is . absent or materially diminished. Under circumstances tin- skin is dry and harsh, more oi pruritic, and inclined to crack or fissure. Cold le the amount of perspiration and heat increases it. and this increase or diminution in the amount of sweat is also influenced by certain drugs which may be readily called to mind. The close connection between the several functions of the kidneys, bowels, and skin may al-o lie mentioned. Certain persons normally sweat but little, even under conditions that ordinarily provoke the secretion, as, for example, in the Turki>ii bath. Anidrosis is usually symptomatic, and is accord- ingly observed in connection with some general or local pathological condition. A general diminution of sweat is frequently seen in diabetes mellitus and insipidus, and in the states of malnutrition dependent upon tuberculosis and the cancerous cachexia, ating is apparently absent in the patches of anesthetic leprosy and in localized areas in sclero- derma, psoriasis, and eczema. The ichthyotic notably suffer in this way. Aubert has made an extended study of the secretion of sweat in various diseases of the skin, to which the curious reader may be referred {Ann. de derm, et de syph., tome ix., ls77-78). The association of anidrosis with various disorders of the nervous system, and as following direct nerve injury, etc., may also be referred to in this place. Lastly, deficient perspiration may be due to simple mechanical plugging of the sweat ducts, the result of uncleanliness. Kaposi declares that there is no absolute anidrosis, the insensible perspira- tion never becoming abolished. This, he states, becomes noticeable as a fluid secretion whenever the skin, however dry it may feel, or even if affected with one of the dry dermatoses (psoriasis, ichthyosis, prurigo), is covered with some material that prevents evaporation. It is certainly true, however, that under certain circumstances, and in limited areas. the sweat glands may be entirely destroyed or undergo atrophy from a variety of causes, or that paralytic conditions arise in consequence of nerve lesions due to the presence of new formations (Geber). Persons with abnormally dry skins are probably more subject than others to inflammatory reactions and to pruritus, especially the type of itching known as pruritus hiemalis. The prognosis and treatment must be based upon the character of the primary cause. In a general way it may be said that the skin should be stimulated by warm alkaline baths and massage. Pilocarpine gives only temporary relief. Cod-liver oil and glycerine 439 Anidrosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES are often prescribed in considerable doses. Unna recommends arsenic and ichthyol separately or together. Five lubrication with fats gives much comfort in ichthyosis. William A. Hardaway. Anidrotics. — See A ntisudorifics. Aniline. — Aniline oil, phenylamine, amidobenzol, C.II.H.N. Aniline is an aromatic amine presenting itself us a thin, oily, volatile, inflammable, colorless fluid of a vinous odor and hot, aromatic taste. It dissolves only very slightly in cold water, but freely in alcohol, ether, and fixed and volatile oils. It is scarcely used in medicine, but its compounds are much employed both in medicine and the arts, and its repeated handling or inhalation results in poisonous effects. The most striking effect seen in aniline workers is cyanosis, due partly to methemoglobin and partly to oilier changes in the blood. It is believed that pig- ment granules in the red corpuscles, or free in the blood, are contributory to the bluish color of the skin. The cyanosis is identical with that produced by acetphenetidin (phenacetin), and the appearance in the urine of para-amido-phenol both from this sub- stance and from aniline shows the close relation be- tween the two chemicals. Following the appearance of the cyanosis there may be a subnormal temperature, shallow respiration, prostration, and even convulsions and coma. The drug may be detected in the breath by its odor. Chronic poisoning shows in anemia, wasting, loss of appetite, constipation, lack of energy, headache, skin eruptions, or sometimes itching of the skin without eruption. Aniline is sometimes used as a solvent for the pure alkaloid, cocaine, for use in the external ear, the usual watery solution of the hydrochloride of cocaine being unable to penetrate the epithelium and therefore useless. W. A. Bastedo. Anilipyrine. — This drug is a combination of one equivalent of acetanilide with two equivalents of antipyrine, and it appears as a crystalline white powder which is fairly soluble in water. It combines the antipyretic and analgesic properties of its com- ponents, and is claimed to be less toxic than either. Its dose is gr. v. to x. (0.3-0.6). W. A. Bastedo. Animal Experimentation. — The Beginnings of Experimental Medicine. — Although Galen had studied functions of nerves by deliberately planned experiments, although centuries later Harvey had "frequent recourse to vivisections" in studying the circulation, and although Hooke, Hales, and Hunter had proved the value of the experimental method in biology, the method was little used in the elucidation of medical problems until about the middle of the nineteenth century. Until that time disease had been studied mainly by observation of the sick. This observation had led, to be sure, to various theories regarding the nature of the causes of disease, such as miasms, the influence of stars, mysterious humors, and vitiated air, but these notions were not put to test in any rigorous fashion. Methods of treatment were founded on these ill-supported notions, and on the experience of persons who tried on human beings, quite irrationally, all manner of curative measures. By tl bservational method alone medicine had made only slight progress in many hundreds of years. The reasons for the failure to test experimentally the notions regarding disease were many. In the first place the experimental method appeared late in Western Europe, even in sciences, such as chemistry and physics, in which it is readily applied. And in biology the difficulties of experimentation were so great and the problems to be unravelled were so com- plex that the application of the experimental method lagged far behind its application in chemistry and physics. The lack of a satisfactory general anes- thetic and of methods for recording with exactness the rapid changes in living organisms were also obstacles to progress in experimentation in biology. It is perhaps significant that the greatest impetus to experimental medicine came from a chemist Pasteur, whose labors established new conceptions regarding the infectious diseases. Fortunately his activities began about the time when ether and chloroform were being introduced to abolish pain in surgical operations. As a result of Pasteur's ideas and experiments asepsis was devised. And nearh simultaneously with these profoundly important con- ceptions and discoveries, the graphic method was invented. Thus within a brief period, about 1S60, a funda- mental and inclusive theory was propounded, and the means were presented for trying on animals, painlessly, without the complications of sepsis, and by exact methods, experiments which could not justifiably be tried first on men. Thus the era of experimental medicine was initiated. And even in the first fifty years of that era the progress in knowledge of organic functions, of the causes of disease, and of new methods of treatment has surpassed that of the previous twenty-three centuries of medical history. This extraordinary advancement of knowledge is doubtless due to the nature of experimentation. The essential characteristic of the experimental method is such control of the conditions affecting the phenomenon which is being examined, as to permit an analysis of the relations normally existing, or capable of existing, between that phenomenon and others. Thus the experimenter deals constantly with factors controlling or modifying the appearance or disappear- ance of phenomena. And as the problems of medicine are precisely problems of control, the results of experimental study have often been immediately practical. The Opposition to Animal Experimentation. — In spite of the benefits to man and to lower animals which have resulted from the application of the ex- perimental method to medical problems, strong hostility to this method of studying disease is felt by persons who designate themselves as " antivivisec- tionists." Their hostility to the use of animals for medical research is, in the main, based on two assump- tions: (1) that pain is commonly inflicted on animals in laboratories to a degree too horrifying to be en- dured, and (2) that no good to man has come or can come from studies of lower animals. In support of the assumption that great pain attends animal experimentation they circulate widely leaflets, pamph- lets, and letters, in which they reveal that they are quite ignorant of the methods they denounce, that they are incapable of interpreting intelligently tin' technical writings of the investigators, and that they let imagination play uncontrolled in describing places they have never visited and procedures they have never witnessed. In support of the assumption that animal experimentation is futile, they quote the hostile statements of medical men long since dead, or, ignoring the overwhelming testimony of practical experience and the consensus of medical opinion throughout the W'orld, they cite the words of so unknown person possessed of a medical degree and desirous of that prominence which comes to one who claims that the earth is flat or the sky a great inverted bowl. However well-meaning the motives of the antivivi- sectionists may be, the literature which they send broadcast has for years been characterized by fraud, trickery, and evil insinuation. These misstatements 440 REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Animal Experimentation l,. n ,. been repeatedly pointed out, bul with no , ,'|,.,. t . in this respect the English antivivisectionists are like the American. The English Royal Commis- sion, which reported in L912, after five years of study and consideration of the subject, declared of the anti- vivisectionists of England thai their "harrowing descriptions and illustrations of operations inflicted animals, which are freely circulated l>y post, ment, or otherwise, are in many cases calcu- lated to mislead the public." The active antivivi- sectionists of both countries, therefore, have sought ough garbled statements, false evidence and in- irate description, to give the impression that almost inconceivable cruelty is involved in animal experimentation, and that the attempt to avoid pain premature death by animal experimentation is in the higl ee futile. Not all antivivisectionists take exactly this view. Seine anion;; them have been SO impressed by the evidence of benefits to man derived from experimental thai they are willing to grant these benefits. ■ till assuming the invoh ement of great pain in the experimental processes they contend that the method is immoral, that it has a brutalizing influence on those who use it. and that it is therefore unjustifiable. holder of this view has stated that he would not have one mouse painfully vivisected to save the great- est of human beings or the life dearest to him. In short, intentional infliction of pain is a sin and crime, and not to be tolerated. views of the opponents of animal experi- mentation raise three quest ions: What is the evidence that animal experimentation has been beneficial in its effects? To what degree is pain to animal- involved? the use of animals for experimentation be justified morally? These questions will be dealt with in order. P.F.XEFITS FROM ANIMAL EXPERIMENTATION. The evidence that animal experimentation has been bene- ficial to man. and to the lower animals also, is found in a wide variety of results. It has given understanding of bodily functions, insight into the nature of many diseases, means of cure based on natural proce^e-. for the detection of infection and for the quali- ties of drugs, knowledge of the action of important new medicaments, and numerous contributions to the practice of surgery. This evidence is now to be a ted. Physiology. — The first of medical sciences in which the experimental method was employed was physi- ry — the science of normal functioning of organs. In judging disease the physician is concerned with the abnormal functioning of organs. Necessarily, there- fore, the judgment of the physician must be based on the normal standard which physiological investiga- tions have revealed. It has been truly said that if there were taken away from physiological knowledge that which is based on experiments on animals, almost nothing would be left. Probably no system of organs in the body more frequently requires earnest study by the physician than the circulatory system. Practically all that is known of the course of events in the heart, the proper interpretation of the cardiac sounds, the factors determining blood pressure, the nervous control of heart and arteries, the intelli- gent treatment of cardiovascular disease — all has resulted from studies on animals. What is true of the circulation is true also of digestion. The activi- ties of a succession of investigators who experimented on animals, have revealed the changes which food undergoes in each portion of the alimentary canal, the nature of the digestive juices, the conditions under which they are poured out. and, to a large degree, the esand character of digestive disorders. Similarly, through the brilliant researches of Sherrington and others, illuminating insight is being secured into some of the intricacies of the nervous system. These and many other notable contributions to physiology, which almost i b 1 1 1 \ stir man's wonder at the marvcl- 0US Organization Oi t he body, an' t he direct OUtCOl if operations on animals. It cannot be too strongly emphasized that almost the entire structure of physiological knowledge on which the modern physi- cian bases his judgment knowledge which in the every-day practice of licine makes all tin' dif- ference between understanding and blind bewilder- ment — has grown from the application of the ex- perimental met hod. Parasitic Origin of Infectious Diseases. — As already stated. Pasteur s ideas of the nature of infection gave the greatest impetus to animal experimentation, [s 1853 his crucial discovery that the fungus, Penicilium glaucum, destroyed dextro-tartaric, but not levo- tartaric acid indicated a. significant and peculiar relation between fermentation and living organisms. His studies disproving spontaneous genera tii n i. under- taken in I860, supported his views mi fermentation. And by actually inducing in the healthy moths of silk worms, solely by feeding them mulberry leaves, the disease which was threatening the destruction of the silk industry in France, he turned his ideas to practi- cal ace,, nut. simultaneously saving France from great economic disturbance, and bringing clear evidence of the parasitic origin of silk worm disease. The infer- ence was logical that other diseases which spread rapidly as epidemics or epizootics are due to living organisms. Thus Pasteur s studies stimulated num- erous other investigators to try to find as active agents in infectious diseases, microscopic germs, or bactera. Through the activity of these men who, like Pasteur, carefully tested their inferences by experiments on animals, the parasitic origin of infectious diseases be- came a firmly established fact. An account of the role played by animals in developing our knowledge of some of the more important of these diseases will illustrate the value of animal experimentation. Tuberculosis. — In 1S43 Klencke had demonstrated the infectious nature of "tubercle" by inoculating rabbits with "tubercle cells" and producing general miliary tuberculosis. Little attention was paid to these experiments, however, until Villemin, in 1S45, repeated and confirmed them, and thoroughly proved the infectiousness of tubercle by reinoculation from animal to animal. Villemin also found that inocula- tion of other morbid material, such as cancer, pus, and bits of pneumonic lung, into rabbits, did not re- sult in tuberculosis, and he inferred that the disease was due to a germ. Although other experiments on animals involving injection, inhalation, and ingestion tests, showed the danger from tuberculous sputum and milk, the identity of scrofulous disease and tuberculosis in man, and tuberculous disease in animals themselves, and proved the value of animal inoculations for purposes of diagnosis, the characteris- tics of the infectious agent were not known until Koch reported, in 1SS2, his discovery of the Bacillus tuberculosis. By rigorously exacting procedures — the isolation of the bacilli in "pure cultures," the production of the disease in animals by injection of the pure cultures, and the recovery from the diseased tissues of the injected animals bacilli in all respects like those injected — Koch brought conclusive proof that tuberculosis results from the growth of this germ in the body. Later (1S90) through animal experiments he demonstrated the value of tuberculin as an aid to the early diagnosis of tuberculosis in man and in cattle, and proposed the tuberculin test, as a practical method of eradicating the disease from infected herds. Through animal experiments Cornet (1S90) proved the danger of infection from the dried sputum of tuberculous patients. Through animal experiments Flugge (1S99) showed the possibility of droplet in- fection from the spray of saliva in violent coughing. Through animal experiments Trudeau (18S6) con- 441 Animal Experimentation REFERENCE HANDBOOK OF THE MEDICAL SCIENCES finned his belief in the efficacy of dietetic and open- air treatment as a means of combating tuberculosis — a treatment now everywhere adopted. Thus all the preventive and diagnostic and curative measures employed in the campaign against tuberculosis are the result of experiments on animals. The new knowledge proved that tuberculosis is notinherited, that because infectious it is preventable, and that in its beginnings it can be cured. These facts , together with the possibilities of early diagnosis, dependent on animal tests, have led to a widespread hope that the disease can be conquered. This hope serins justified by the decline in death rate from tuberculosis in various parts of the world since hygienic measures began to be adopted. During the twenty years before Koch's discovery of the tubercle bacillus (1SS2) the death rate from tuberculosis in Boston was forty-two per 10,000; during the twenty years following the discovery the rate gradually fell to twenty-one per 10,000 — a drop of fifty per cent. It has since fallen to less than eighteen per 10,000. In New York City the death rate from tuberculosis dropped forty per cent, between 1882 and 1902. In Prussia the death rate was fifty per cent, less in 100:; than in 18S5. In Edinburgh, after partial hygienic measures had been enforced, the death rate was seventeen per 10,000 in 1897; during the following decade, by cooperation of the agencies tending to control the infection, the death rate was reduced to eleven per 10,000. These bare statistics imply an immense reduction of mortality throughout I ln- civilized world — a saving of lives, furthermore, in large degree for the years of service and working efficiency. The alternative to these great achievements has been vividly stated by Trudeau (1909): "If it were not for the knowledge which science has won by animal experimentation in the field of this disease in the last twenty-five years, we should still be plunged in the apathy of ignorance and despair toward it, ami tuberculosis would still be exacting its pitiless toll unheeded and unhindered." Bubonic Plague.- — The terror of the Black Death is well founded in man's experience with the pesti- lence. Defoe, in his "Journal of the Plague Year," in London, tells how the streets became hushed as the infection spread insidiously from parish to parish, how the carts moved about at night receiving the heaped bodies of the dead, and how the bodies were dumped pell-mell and by hundreds into huge pits dug for their burial. Thousands died week after week in London alone. What was true of London in 1665 has been true of every other large population in which the plague has raged without control. In one year, 1905, the number of recorded deaths from plague in India was 1,040,429. It has wrought disaster and desolation in China and other portions of the orient in similar degree. Because of increased knowledge of the disease, largely gained by animal experimentation, plague in any well organized community can be promptly controlled and even eradicated. Attending the large increase in commercial relations with the orient, epidemics have started in recent years in several great seaports — Oporto, Rio de Janeiro, Glasgow, Liverpool, San Francisco, Seattle, and others — but have been promptly stopped by radical measures. In India, however, opposition to the sacrifice of animals, and in China ignorance and apathy, have hitherto prevented application of the knowledge about plague which animal experiments have yielded. The first step in the conquest of the plague was taken in 1894 when Yersin and Kitasato, working independently, discovered the Bacillus pestis. The concomitance of an epizootic in rats and an epidemic of plague had been previously noted, but no causal relation had been established between the two. In 1898, Simond found that fleas placed on a plague- 442 infected rat drew blood containing the plague bacillus and that these fleas transferred to a healthv rat could transmit the disease. Then it was shown that healthy rats and guinea-pigs failed to take the disease from infected animals, if fleas were absent. Later, monkeys placed in cages to simulate human beings were found infected by rat fleas. These animal experiments led to observations on human conditions, especially in India, which indicated that the great majority of cases of plague are due to infection of man from rats through rat Ilea-. This knowledge revolutionized the methods ef dealing with an epidemic of plague. When formerly the prevalence of the disease was attributed to climatic conditions or soil infection, intelligent measures for the suppression of the epidemic were impossible. Now rat traps are set, rookeries and vermin-breeding hovels are torn down, and the victims already infected are isolated so that they shall not be the occasion for further spreading of the disease. The part played by animal experimentation in tracing the relation between the pneumonic ami bubonic type of plague, in assuring diagnosis, and in the development of prophylaxis and treatment of individual human beings cannot here be considered. It is sufficient to point out that through the knowledge which has been secured the panic and terror formerly induced by the Black Death have been reasonably dissipated — a deliverance from bondage for which mankind is indebted wholly to experiments on rats, guinea-pigs, and monkeys. Diphtheria. — The search of the internal organs of diphtheria patients by Klcbs (1881) revealed no constant presence of bacteria. Two years later he demonstrated small rod-shaped bacteria in micro- scopic sections near the surface of the diphtheritic membrane, but with these were various other kinds of bacteria. It was necessary, therefore, to test experimentally for the organisms which excite the production of the membrane. By feeding and inoculating various animals with pure cultures of the accessory bacteria, Loeffler (1884) was led to the conclusion that these forms are of secondary import- ance. With pure cultures of the rod-shaped bacteria Loeffler was able to reproduce both in guinea-pigs and rabbits characteristic, grayish-white, tough, false membranes. And since the bacteria were found only at the seat of inoculation, and not in the orgs the inference was drawn that a poison produced at the seat of inoculation must have circulated in the blood. By these experiments on animals the role of the Klebs-Loeffler or diphtheria bacillus in the production of the disease was definitely determined. Loeffler's idea that the general bodiiy disturbances in diphtheria are due to circulation of a soluble poison or toxin was substantiated by Roux and Yersin, who found that filtrates from bouillon cultures of the Klebs-Loeffler bacillus produced the same changes in guinea-pigs as were produced by infection with the bacteria, and were highly toxic in small doses. By tests on guinea-pigs, also, the identity of fatal croup with diphtheria was established, mild cases of the disease were discovered, and the bacteria were demonstrated in the throats of some persons who had recovered from the disease and who as "bacillus carriers" were capable of innocently spreading the infection. Thus by animal experimentation the bacteria which excite diphtheria were discovered, the manner in which they produce their effects was indicated, and some of the methods of extension of the disease were made clear. All this information was highly valuable for the intelligent management of diphtheria patients. More important than these discoveries, however, was that which gave insight into the mechanism of immunity. In 1890 von Behring and Kitasato found REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ niiii.ii Experimentation that laboratory animals, injected with weakened toxin-, became immune to doses of the whole toxin that were fatal to the normal animal. < H still greater practical significance was the demonstration that the blood of the actively immunized animals injected into normal animals would protect these animals against later injections of fatal doses of toxin, or would cure, within reasonable time limits, animals that already l,. 1( | received a fatal dose. That the toxin was neutralized by a definite antidote or antitoxin was shown by mixing the toxin « it li some of the protective hi | or serum in vitro. The poison wa thus com- ely counteracted, and when the mixture was in- ed it had no harmful effect whatever. ese experiments on animals were t he basis of the antitoxin treatment of diphtheria. A horse is Ln- ed with diphtheria toxin, and when he has devel- oped in his blood the maximum amount of antitoxin, he is bled, and the serum of the blood, which contains the antitoxin, is prepared for use in cases of diphthe- ria. Thus the natural antidote to the poison pro- duced by diphtheria bacilli is injected into persons by the disease, and the persons are pro- nn the action of diphtheria toxin just as were laboratory animals studied by von Behring and Kitasato. Antitoxin is useful both for the prevention and the treatment of diphtheria. Numerous instance been reported in which diphtheria has broken out in large institutions, and been promptly checked by rophylactic injection. In a large insane asylum near New York City an epidemic started in the sum- mer of 1910. Many cases among doctors, nurses, and patients developed within a few days after the discovery of the first case. As soon as possible over 2,000 members of the institution were given antitoxin (1,000 units each). No immunized person was at- tacked and the epidemic was stooped in less than a week. When antitoxin is used for treatment of diphtheria, it does not restore to a normal state tissues that already suffered serious injur}' — it acts solely as a preventive of further poisoning. Its efficiency, therefore, would be expected to be greatest when it is administered on the first days of an attack. Such is the fact. In the Hospital for Contagious Diseases in New York City, in 218 cases of diphtheria treated with antitoxin on the first day, there were no deaths; in 1,153 cases treated on the second day, the death rate was 4.59 per cent.; in 880 cases treated the third day, the death rate was 12.50 per cent.; and in 59S cases treated on the fourth day. 16.4 per cent. These results have been duplicated elsewhere, both in in- stitutions and in private practice. Because of the prevalence of epidemics the mortal- ity statistics from diphtheria for any one city for the period of a few years will show variations which do not permit proper conclusions to be drawn. By taking the records of death from diphtheria and "croup" from nineteen large American and European cities fin which records are carefully kept), from 187S (fifteen years before antitoxin was introduced) to 1908 (fifteen years after), W. H. Park has largely eliminated these errors. Although marked fluctua- tions of the absolute mortality per 100,000 population occurred in the preantitoxin years, in no period did all the cities show a decrease. Not until 1894 did all the cities begin to show uniformly a decrease in the mortality per 100,000. Furthermore this drop has continued until the present — a betterment doubtless due to more extensive use of antitoxin, and to recog- nition of the value of large doses and of early treat- ment. In 1894 the average mortality in these cities was 79.9 per 100,000; in 1907 it was 17 per 100,000 population. This difference is so great, the time of its beginning so clearly coincident with the beginning of antitoxin treatment, and the betterment of results so progressive since that time, that it is difficult to give any other explanation than that the saving of life was due to antitoxin. Clinical observati I p iti ho appear without having had antitoxin treatment indicates that there ha been no marked change in the average virulence of diphtheria Clinical experience has from the beginning testified to the remarkable specific effect which antitoxin has in checking the course of the di ease. Hospitals for the care of diphtheria patients througl t the world employ antitoxin treatment. States manufacture antitoxin and provide it freely for the inhabitants. Thus the action ol individ > and communities supports the results of animal experimental ton. In 1894 the number of deaths from diphtheria in the nineteen large cities previouslj referred to was 15,1 25; then the steady drop began, and in 1904 the number oi deaths was 1,917. In ten pear there had come a red in i i f more than 10,000. This great aving of human lives, which is to continue indefinitely, is the direct re ult of experiments on animals, and the I ions which horses have to undergo in suppl antitoxin. Epidemic Cerebrospinal Meningitis.— Epidemic meningitis has in the past brought consternation to the laity becau e of its mysterious onset and its terribL and has brought distress to the phy- sician n of his helplessness in its presence. The first step in the conquest of the disease was taken when Weichselbaum discovered, in 1887, the menin- ii cus which is always associated with tin- disease. The final practical -tip was taken in 1906 — 1907, when Flexner announced the effectiveness of intradural inoculations of antimeningitis serum. Attempts to use the serum subcutaneously in human cases had previously been made in Germany, but had proved unsatisfactory. The reasons for this failure appeared when the problem was attacked experimentally. Flexner found that the disease could be induced by injection of active cultures of the meningococcus subdurally in certain species of lower monkeys. The antimeningitis serum was found to have (1) the power of stopping the growth of, or destroying outright, the meningococci, (2) the prop- erty of increasing phagocytosis and intracellular digestion of these bacteria, and (3) the ability to exert a neutralizing action on the toxic products set free by their growth and disintegration. Weak dilutions of the serum have little or no effect, however, in destroying the meningococci — the serum must be applied in full strength at the site of inflammation. When administered by lumbar puncture to monkeys sick with epidemic meningitis, the inflammatory process was stopped, the meningococci were de- stroyed, and the monkeys were quickly restored to normal condition. Furthermore, no perceptible in- jurious effect resulted from the serum itself. By further animal experiments it was proved that injection of, first, heated and later, living cultures of the meningococcus into a horse, the animal became immunized, and his blood serum rich in curative properties. The mortality from this disease (in cases which received bacterial diagnosis), wherever it has been studied, has ranged from sixty-eight to ninety-one per cent, with an average of about seventy-five per cent. It has been highest in infants, ranging between ninety and one hundred per cent. In 1909 Flexner analyzed 712 cases which had been treated by the antiserum prepared under his direction. The mor- tality among children under three years of age (104 eases) was 42.3 per cent. From two to fifteen years (326 cases) it was 23.4 per cent. After the fifteenth year it was thirty per cent, and over. As in diph- theria, the mortality is less if the serum is used early in the attack. In 180 cases injected within the first three days the mortality was 25.3 per cent.; in 179 patients injected between the fourth and seventh day 443 Animal Experimentation REFEREXCE HANDBOOK OF THE MEDICAL SCIENCES it was 27. S per cent.; whereas 129 injected later than the seventh day had a mortality of 42.1 per cent. In seventeen children under two years of age injected within the first three days of the illness only one died! Similar results have been attained in Germany and France with serum prepared in those two countries. In general by methods < leveloped in animal experimen- tation the percentages have been reversed — from about seventy-five per cent, mortality to about seventy-five per cent, recovery — with a resultant saving of fifty lives in every hundred cases. Besides the saving of life there is a noteworthy abatement of the symptoms of the disease. Within twenty-four hours after the serum is injected there is often a permanent return of consciousness, disappear- ance of the mental dulness or delirium, removal of the racking headache, relief of the hyperesthesia, control of the vomiting. "To see patients pass within twenty-four hours, after one or two injections of the scrum, from a state of great distress or unconscious- ness to one of almost normal mentality is something the impressiveness of which is not easily to be over- estimated." (Dunn). When one considers that epidemic meningitis is an infection tending to a fatal termination or to a prolonged course with frequent relapses, this rapid change (about twenty-five per cent, of recovery in treated cases is by crisis) is one of the most important results of the new treatment. A still more important result, however, is the ab- sence of disabling permanent sequelae of the illness. In former times deafness, blindness, paralysis, and idiocy were not unusual consequences of epidemic meningitis. To increase the percentage of recovery, while leaving the percentage of fixed sequelae un- changed, might not be regarded as a blessing. Clin- ical observations, however, show that serum-treated patients, who recover, rarely have the serious handi- caps which afflicted those who recovered in pre-serum days. Some instances of deafness which nave been reported were noted as already present when the serum was injected. In the animal experiments which led to the present serum treatment for epidemic meningitis Flexner used about twenty-five monkeys and perhaps 100 guinea-pigs. Already records of approximately 1,000 cases treated by this method imply a saving of 500 human lives — unafflicted with blindness, paralysis or mental defectiveness. Pus and Pyemia. — Within the memory of surgeons still active, pus was regarded not only as a natural product of the healing process, but as a needful accompaniment. In amputations the ligatures tied about blood-vessels were left hanging from the lips of the wound; soon they were covered with pus which poured from the cut surfaces; the patient tossed about the bed, sleepless with pain, fever, and thirst; from time to time the ligatures were pulled upon to determine whether they had "rotted" loose; not infrequently the tied artery was not closed when the ligature was pulled away or loosened by inflammation, and serious secondary hemorrhages followed; from ten days to three weeks were required for the ligatures to rot loose, though they might remain and keep the wound open for months. The long convalescence \\ as complicated in many cases by erysipelas, lockjaw, blood poisoning, or hospital gangrene. Hospital gangrene in the Civil War had a mortality of 45.6 per cent.; lockjaw 89.3 per cent.; and pyemia or blood poisoning 97.4 per cent. Of these complications of wounds there were thousands during the War. Wounds of the knee-joint followed by amputation had a mortality of fifty-one per cent., and without amputa- tion sixty-one per cent. About sixty-six per cent, of patients with compound fractures were sure to die. To open the cranial case or the abdomen was an operation of extreme risk, so certain was fatal inflam- mation to follow. The revolutionary change in surgery in the last 444 forty years is traceable to Pasteur's work on fermenta- tion. Struck by Pasteur's studies Lister began inves- tigations which led him to the use of phenol sprays to keep out of wounds the pyogenic cocci. Beginning with compound fractures and abscesses, lie obtained such extraordinary success that he felt justified in trying his methods in surgical operations. By means of experiments on animals he developed the means of tying arteries with embedded catgut ligatures. Later, to be sure, what is now known as surgical cleanliness, asepsis, took the place of antisepsis. But the later development grew out of Listers demonstration of the possibility of healing without pus, if bacteria are excluded from wounded surfaces. What a marvelous change these conceptions and experiments have wrought! With catgut ligatures the wound is closed at once, the ligature i> absorbed, the wound heals in less than a week with little, if any, immediate suffering and with none of the old compli- cations. Pyemia has almost wholly disappeared, lockjaw is heard of only occasionally after accidental cuts which have not been cared for, and erysipelas after operations is exceedingly rare. Compound fractures and opened joints heal as if there had been no break in the skin. Arteries can be tied anywhere without fear of secondary hemorrhage. The body cavities are now opened for surgical conditions with- out serious risk. In short, the evolution of asepsis has brought to pass the most momentous revolution in the entire history of surgery — a revolution which is of immeasurable benefit to mankind and the lower animals as well. Surgical Technique. — The advancement of surgery has depended on animal experimentation not only in the development of asepsis, but also in the devising of operative procedures. Physiological experimi on monkeys have shown the surgeon where to operate on the human brain. Experiments on dogs and cats have shown how nerves regenerate, the proper met hod of suturing cut nerves, and the possibilities of cross-suturing nerves of different function — a proced- ure now being employed to obviate facial palsy. The principles to be followed in suturing the severed bowel were discovered on animals. The amount of small intestine that maybe removed without endan- gering life was also learned by animal experimentation. The same may be said of the removal of kidney sub- stance, of spleen, of lungs, liver, and other viscera. The surgery of the widely opened chest has been the direct outcome of Sauerbruck's studies on the effects on animals of differential intrapulmonary pressure. Through experiments on animals the surgery of blood- vessels has been perfected to such a degree that now the effects of hemorrhage, or the requirement of fresh blood, can readily be met by transfusion. What the future may hold for surgical ability can perhaps be conjectured. Already in animal experiments, organs such as kidneys and ovaries have been im- planted and have continued functioning; pieces of blood-vessel, preserved for w-eeks in the cold, have been sewn into gaps in large arteries with no per- manent disturbance of the circulation; parts of joints have been introduced and established in the new- surroundings. These instances must be regarded as merely hinting the part played by animal experi- mentation in the advancement of surgery in the past, and now being played in the present progress of surgical art. Many other instances might be cited. Enough has been stated, however, to indicate that death, distress, and enduring pain have been incal- culably lessened by the application of experimental methods to surgical problems. Puerperal Fever. — In preantiseptic days puerperal fever ravaged the lying-in hospitals throughout the world. It was estimated that 30,394 deaths from this disease had occurred in the Paris Lying-in hos- pitals up to 1S64. From 18(50 to lsc.-i the death rate in the Maternite (Paris) was 12.4 per cent., and in REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Animal Experimentation December, 1864, it rose to the appalling height of fifty-seven per cent, [n the sixty years ending with [895, the number of deaths from puerperal lexer in Prussia alone was 363,6241 On the assumption thai each marriage would resuh in four or five children, it was estimated thai every thirtieth married woman in Prussia would fall a victim. In the United States serious outbreaks occurred which were bej I control; in the Bellevue Hospital in 1S7'_' an epidemic occurred with a mortality of eighteen per cent. In all countries the usual death rate ranged between two and seven per cent. Although Gordon (1792) had staled that he had himself been the " means of carrying the infection to a freat number of women," and Oliver Wendell [olmes (1843) had argued that puerperal fever wa '• a private pestilence, " and Semmelweis (1847), after presenting evidence that the affliction was due to contamination of patients by the soiled hands of the obstetrician, had greatly reduced the mortality by insing his hands in a solution of chlorinated lime, liscrepancy of opinion on the subject long con- tinued to prevail. The condition was regarded as unavoidable, and was attributed to cosmic, atmos- pheric or telluric influences, the fainted air of old wards, the power of mind over body, the visitation of Providence, and to various other conditions. Not until about 1875, when Lister's views of wound in- fection began to receive attention, was credit given to bacterial origin of puerperal fever. And not until Pasteur, in 1879, had cultivated the streptococcus from cases of puerperal infection and demonstrated on animals its power to produce blood poisoning, was there general acceptance of the opinions long pre- viously urged by Gordon, Holmes, and Semmelweis. By means of surgical cleanliness, which is practical bacteriology directly dependent on animal experi- mentation, the mortality from puerperal fever has been greatly reduced. In 1909 Markoe reported 60,000 births in the Xew York Lying-in Hospital with a mortality of 0.34 of one per cent.; Pinard reported 15,633 deliveries between 1890 and 190S with a mortality of only 0.15 of one per cent.; and Mermann in 1907 reported on S.700 patients delivered ler his supervision with a septic mortality of only 0.0S of one per cent! In other words, death from child-bed fever litis fallen from the former usual rate of four or five in every hundred mothers to approxi- mately one mother in 1,000. As Williams has said, " Had animal experimentation led to nothing more than the discovery of the bacterial nature of puer- peral fever, whereby a means was provided for doing away with its former hideous mortality, it would abundantly justify the sacrifice of all the animals which have thus far been used for experimental purposes." Pharmacology. — The whole modern science of drug relation and drug action is founded on animal tests. The pharmacologist is a chemist studying the chemical character of substances, and a biologist studying tin 1 action of these substances on living organisms. Such experimentation on animals has yielded all the sopor- ifics (chloral, sulphonal, trional) that have been dis- covered during the past forty-five years. It has yielded also all the local anesthetics, such as cocaine and eucaine, which render painless small surgical operations. All modern drugs which reduce fever fantipyrine, acetanilide), the diuretics caffeine and tl bromine, the emetic apomorphine were all intro- duced by animal experimentation. Adrenalin also was thus found. During experimentation on animals aniyl nitrite was discovered, the only drug giving prompt relief from the severe pain of angina pectoris. Through animal tests some drugs have been proved worthless and have been discarded. Others have had their action more precisely defined — digitalis is an example. Others have been proved harmful. With still others animal tests have been used to stand- ardize the action. Thus no method of chemical anal- ysis has been devised to determine the efficiency of a given preparation of ergot. The manufacturing ehenii t has to resorl to ti physiological tesl of every specimen of ergol which he uses. Any woman who takes ergot for I he control of hemorrhage becomes thereby the recipient of benefits from animal experi- mentation. The future growth of our knowledge of alterations which drugs Can pro, Inc.- in the body, whether normal or diseased, must either depend on experiments performed on animals or be tested firsl on human beings. There is little question which is (he more justifiable procedure. Syphilis and Salvarsan. — One of the most interest- ing examples of the use of animal lor the study of drug action is found in Ehrlich's discovery of salvar- san as a treatment for syphilis. Of the calamitous nature of syphilis little need here be stated. It may kill in its acute slage, or pave the way for other dis- ease, or lead lo mental degeneration; it may cau-e an e 'mously high mortality in still-births and abor- tions; it may result in the production of wizened offspring lacking in vitality and subject to infections, or idiots, or monsters, or those unfortunates whose syphilitic heredity falls as a blight upon them in their youth and is passed on as a scourge to their descendants. Although clinical study had revealed many of the characteristics of syphilis, knowledge of the disease was lacking in several important particulars. It was impossible to make an early diagnosis; and diagnosis in the late stages or in "latent" forms was often extremely difficult. Furthermore no one could tell how long treatment must be continued before a complete cure was obtained. All of these deficiencies in knowledge of the disease were of great social importance. Fortunately through animal experi- mental i. and rotates very -lightly to the left. At a temperature of from 15° to 19° C. it congeals. More than ninety per cent, of it is anethol (y.r.). which gives its properties, and which may the more advan- ously he employed. a< uniformity is thus secured. It belongs to the more carminative class of volatile oils, and shares the diffusive stimulant properties of volatile oils in general. It is. at the same time, of an unusually pleasant flavor and much used for purely 'ring purposes, especially as an addition to liquors. [ta pleasant flavor also makes it of special use in treating the flatulent colic of infants, and in adding ti> medicines which have a tendency to gripe. The dose is ntiij. to xv. The official preparations are the Aqua, of one-fifth of one per cent, strength, and the Spiritus, of ten-per-cent. strength. The Spiritus Aurantii Compositus contains one-half of one per . and the Tinctura Opii. Camphorata two-fifths of one per cent. It also flavors several other peparations. H. H. Rusby. Anise, Star. — Illicium. "The fruit of IUicvum ri rum Hook. (fain. Magnoliacece)" (U. S. P.). The cies here named is the Chinese, or sweet star anise. besides which there is a poisonous Japanese species. When I.inne applied the name /. anisatum, supposing that he had the former, he really had the latter, as his description and figure clearly show. As a result of this mistake, the poisonous species must always bear the inappropriate name I. anisatum L. (Syn.: I. religiosum Zucc), and Hooker's later name, I. vcrum, pertain to the useful species. The plant is a handsome small tree. The fruit consists of the eight carpels, united to a carpophore, from which they can be easily separated, hut distinct from one another. Each carpel is short, laterally compressed, "boat-shaped," pointed at the upper and outer cxtremitv. and dehiscent at the upper and inner border. The pericarp is deep brown, rather woody, brittle, fragrant, and spicy. The seeds, which can !><■ seen through the -split jn the carpel, although this is not usually wide enough to lei them fall out, are also brown, but very smooth and shining. They are less fragrant than the carpels, hut. contain considerable fixed oil in their kernels. Both te la and pericarp show, under the mici pe, numerous oil cells, and the parenchyma of the seeds re\ eals drops of fat. Composition.-- Re-ides sugar, gum. and fixed oil, which, although abundant, have no practical value, tar anise is remarkable for containing a large percentage (from three to live) of an e- I niial oil, SO Fig. 2-ts — TUicium verum or Star Anise, n. Flower; 6. gyneecium; c, fruit; d, seed, entire,; e, seed in longitudinal section. similar in odor, taste, properties, and composition to that of anise, that no means can be relied upon to distinguish them from each other, except by the greater percentage of anethol in the latter, on account of which it congeals at a higher temperature. Illicium is never prescribed, and is recognized only as a commercial source of "oil of anise." This oil, owing to its weaker action, should not be indiscriminately substituted for oil of anise. H. II. Rusbi . Ankistrodon. — A genus of snakes containing two of the most poisonous species in North America — ■ .1. contortrix, the copperhead, and A. piseivorus, the moccasin. A. S. P. Ankle Joint. — As this joint (Articulaiio talocruralis, UNA) supports the weight of the body, considerable stability is required of it. This is secured mainly by the shape of the articular surfaces, which interlock like a mortise and tenon. The tibia and fibula, strongly united by ligaments (interosseous and infe- rior tibiofibular, Figs. 1214, 215, and 21S), form the mortise by embracing with their extremities (malleoli) the tenon-like astragalus. The joint is a hinge, its movement angular, and in a single oblique plane I corresponding to the outward pointing of the toes) through an arc of some eighty degrees. A slight anteroposterior ridge on the tibia fits into a corre- sponding depression on the astragalus giving a "trochlear" character to the joint. The arc of the astragalus is from a circle somewhat smaller than that of the tibia, but it comprises about one-third of the circumference while the tibia has not more than one- fourth. While standing erect the facet of the astrag- alus is partially uncovered in front and behind and there is a slight interval between the curves at these points. In the fetus of six weeks (Henke and Rey- her) the joint is arranged like that of some marsupials, so as to admit of rotation, the astragalus sending a process up between the tibia and fibula. To guard Vol. I.— 29 449 Ankle Joint REFERENCE HANDBOOK OF THE MEDICAL SCIENCES against the thrust of the tibia and fibula when alight- ing on the extended toes (the commonest form of dislocation arises thus), the astragalus is narrower be- hind than in front, averaging 35 mm. behind and Interosseous liga- ment. Ext. lat. ligament. Synovial cavity. Deltoid ligament. Tarsal canal with astrag ealcanean ligament. Fig. 249. — Froutal Section of Right Ankle. 40 mm. in front. It is doubtful whether lateral movement is possible within the joint itself, that which apparently occurs being really due to the play of the small bones of the foot upon each other. The Post, tibio-fibular ligt. Ext. lat. ligt. Deltoid ligt. Post, astrag. calc. ligt. Fig. 250. — Rear View of Left Ankle. malleoli are held against the articular surfaces in all positions by the elasticity of the shaft of the fibula which bends inward when the wedge pushes the malleoli apart, springing back during extension. The Long plantar ligt. Tarsal canal and astrag. calc. ligt. Fig. 251. — Sagittal Section of Right Ankle. axis of rotation of the curved superior surface of the astragalus (Fig. 251) passes through the most fixed part of the bone, viz., the tarsal canal, touching the outer malleolus but passing below the inner, which does not descend so low (Figs. 249 and 250). The original capsular ligament (see Arthrology) re- mains in front and behind as a thin and somewhat lax layer of fibers connected with the synovial mem- brane and strengthened by the extensor tendons in front and the tendon of the flexor longus hallucis be- hind. Effusion into the joint usually shows first in front. On the sides strong bands are developed. The internal lateral ligament (Figs. 249, 250, and 252), also called the deltoid, from its triangular form, is the strong- est of these; in dislocations usually tearing the bone apart. It is a thick bundle, ensheath- ing the internal malleolus and passing to the calcaneum, the astragalus, the scaphoid, and the calcaneoscaphoid ligament. Although these are not dis- tinct from each other they have received special ■■-- , Long plantar ligt. Inf. calc. scaphd ligt. Fig. 252. — Inner Side of Right Ankle. names (ligamenta calcaneotibiale, talotibiale anterhis, talotibiale posterius, and tibionaviculare, UNA). The tendon of the tibialis posticus strengthens it. Deeper fibers also pass to the astragalus (ligamentum taloti- biale profundum). In amputating at the ankle the joint is opened on the inner side, because of the short- ness of the malleolus, and the existence of this deep band should be remembered. The external lateral ligament (Figs. 249, 250, and 253) is composed of three Post. Post. Middle Ant. hand. band. band. Ext. lat. ligt. Fig. 253.— Outer Side of Right Ankle. distinctly separate bands which radiate from the lower part of the malleolus, the anterior and posterior bands passing to the astragalus, the middle one to the calcaneum. The names of these are quite similar to I hose of the internal ligament, viz., ligamenta talo- fibulare anterius and posterius, and calcaneofibulare. The synovial cavity is quite extensive, communicating above with the inferior tibiofibular articulation. It is said to contain more synovia than that of any other joint (Morris). Its capacity is not affected by the 450 REFERENCE HANDBOOK or Till: MKDICAI, SCIKXt ES Ank> losls position of the foot, and no change of posture lake.-- place during inflammation of its membrane. Sensations of pain are sometimes fel< in t ho ankle without lesion of the joint, caused by some injury to the long nervous trunks which supply it, viz., the long saphenous, connected with the lumbar plexus, and the anterior tibial (deep peroneal BNA), with the sacral us, The vascular supply arising from twigs from the anterior and posterior tibial arteries, ami dis- trging by both saphenous veins, may be interfered with by tight boot laces and occasion a dull pain. FltANK BaKEK. Ankylosis. — Synonyms: English, Stiff joint, fixed joint; French, Roideur articulaire; German, Gelenk- verwachsung, Gelenksteifigkeit. A strictly correct definition would designate a i angular position of a joint, but this restriction i i . longer obtains, t he word now being used to describe joints that have become more or less stiff in any position. Qualifying terms are used to indicate the extent of the stiffness, such as false, spurious, true, bony, ligamentous, partial, complete, incomplete, all of which can be best understood with the i i possible confusion if the word ankylosis is ed as a synonym for stiffness. i: piologt. — Traumatism, gonorrheal rheumatism. uration in joints, tuberculous osteitis, tuberculous 01 itis, syphilitic affections of joints, long fixation ii a fracture is near or extends into a joint, 1 is deformans, etc. Pathology. — In complete, i.e. bony ankylosis, the bones forming a joint are limited by callus in the same manner that union takes place after a fracture in the shaft of a long bone, or bridging by callus takes eat one or more places around the joint. Usually us ankylosis is preceded by a more or less pro- longed stage of fibrous or cartilaginous union. In IUS ankylosis bands of fibrous connective tissue unite the bones forming a joint, thereby limiting the motion. Accordingly as these bands are short or Jung t he stiffness is complete or partial. In cases of joint stiffness produced by extra- articular, fibrous, tendinous, or cicatricial contracture, the joint remains free from adhesions for years when it has not been involved in inflammatory action. Diagnosis of bony ankylosis is usually unattended with difficulty except where there are a number of joints near together, as, for example, the carpus, tarsus, and spine. This limitation of motion in one joint is generally compensated for by excess of motion in another, thereby rendering all the surrounding parts capable of functionating in a very nearly normal manner. Fibrous ankylosis is more difficult to discern, especially if pain accompanies the required manipu- lative procedures. It is most apt to be confused with fibrous, ligamentous, or cicatricial contractures of soft parts outside of a joint, but having direct functional relations therewith. Extraarticular con- tractions may often be differentiated by the existence of resistance to free joint motion in one direction only, i.e. that produced by the contracture, while the joint moves more or less freely in other directions. Muscular contracture, whether voluntary or invol- untary is but temporary, and the rigidity of the surrounding parts is clearly discernible. U muscular rigidity is one of the most important and reliable symptoms of joint inflammation, it is a serious error to anesthetize a patient for examination oi a joint until the absence of muscular fixation has been clearly proven. In such cases the anesthetic relaxes the muscles, leaving the joint free for move- ments which are seriously prejudicial and which were instinctively guarded against by the patient. If there has been no muscular fixation much may be learned by I lie careful study of a joint while the patient is unconscious, h ran be definitely deter- mined whether it is ankylosed or only partially The yielding of the soft part above and below the joint suspected may be prevented by tightly bandag- ing them, the joint itself being left uncovered. Treatment. — The most important part of the treatment lies in prophylaxis, prevention of the occurrence of ankylosis, or, if it is inevitable, in o disposing the parts that the best position for future usefulness may be obtained. The trend of modern surgery is greatly to shorten the time oi fixation of a fractured bone, in the effort to avoid impaired joint function, as well as to secure a freedom from mn cle atrophy. The earlier application of passive motion and massage is being resorted to, and many of the serious deformities which formerly followed fractures are now less frequently seen. Bach individual joint has special features and presents special difficulties that must be carefully considered in applying any form of treatment. The st useful position for a stiff joint is still subject to discussion ; no general rule can be laid down. Fibrous or incomplete ankylosis may require attention to overcome a faulty position, or to increase the extent. of the mot ton. This is to be accomplished by passive motion made in the direction of the normal action of that joint. Brisement force, is a term applied to the use of such force as the surgeon can judiciously apply, bearing in mind the danger of breaking the shaft of the bone used as a lever or of producing a separation of the epiphysis. It is wise to begin all manipulations well within a safe limit, and gradually to increase the power employed as the range of motion increases; remembering that the strength of the long bones often diminishes from disuse and that they will break if a sudden corrective force is applied. The above methods are greatly facilitated by pre- viously subjecting the limb to dry hot air at a tem- perature of from 300° to 400° F. for an hour. For this purpose some one of the many forms of ovens made for the purpose may be employed. Care should always be taken to wrap thoroughly the parts in flannel, but never in cotton. The latter is highly inflammable and holds the moisture. The interior of the oven should be kept as dry as possible, as the perspiration, which is often profuse, renders the atmosphere within the oven moist, and is apt to result in scalding the patient. Ovens are now made for use with alcohol, gas, and electricity as means of generating heat. Each has its peculiar advantages, but the results are not different. The effect is to soften the fibrous adhesions very much in the same way that old glued joints of wood are softened, enabling the surgeon to obtain movements of a partially stiff joint with very much less force and therefore, with less danger and less pain. The pain accompanying corrective manipulations following the use of the oven is generally inconsid- erable, although varying greatly in different subjects. When the pain is very great, the employment of an anesthetic that acts quickly enables the operator to proceed with greater despatch. The anesthetic that I have found most satisfactory for this purpose is ethyl bromide; ethyl chloride is also satisfactory. I have also used chloroform and at times nitrous oxide gas. Fixation appliances of any kind are contraindicated during corrective procedures in fibrous ankylosis, as increased freedom of movements is desired rather than fixation. Voluntary motions are to be encour- aged to increase the mobility and to regain the muscle function which is required for proper use of the joint. The employment, of electricity has been extolled for its effect in restoring lost or impaired muscle function, and when used by skilful physicians it is 451 Ankylosis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES more likely to produce the desired effects than when crudely applied by a more or less non-medical attendant. Massage is a means of restoring impaired muscle power that should not be overlooked, and, like all other therapeutic measures, should be carefully prescribed as to methods and time. The object sought should be the voluntary control of the affected joint and the mechanism that actuates it; this should be impressed on the patient. In true ankylosis the object sought is the most useful position of the parts, and here careful study is necessary to avoid attempting to obtain a movable joint when greater usefulness could be had from a stiff joint in an approved position. The greatest diversity of opinion exists as to the most desirable position for ankylosed joints. In the elbow a fully extended position of the arm is generally conceded to be the least useful, while the exact angle of flexion has been the cause of much discussion. Some advocate a right angle, others a lesser angle, to enable the patient to bring the hand to the mouth; and yet any rigid position is more or less conspicuous and cumbersome. The hip when ankylosed at various angles can be made useful by the increased latitude of motion im- parted to the other hip-joint and to the lumbar verte- bral articulations. To such an extent is the lower spine reciprocal in loss of function of one or both hip-joints that it has been called the third hip-joint. Ankylosis of a hip at right angle to its fully extended position has frequently been observed to be useful for progres- sion. The third hip-joint has also developed in efficiency in cases in which a hip-joint was ankylosed in the most approved position, i.e. that of almost full extension, facilitating the movements of the entire pelvis in walking and especially in sitting, and approaching very closely normal action. The arguments in favor of a fully extended leg versus slight flexion in cases of bony ankylosis of the knee appear to be about equally divided. _ The sl'ghtly flexed leg is certainly somewhat less in the way in sitting, and it enables the patient to develop a more graceful carriage, but all of these are cast into insignificance by the mechanically faulty position of flexion. Ashhurst refers to a case in which the knee remained straight with apparent bony union for eight years and then began to yield, and within a year was bent to a right angle and rotated. The fully extended or straight position is less liable to bend because its weight-bearing function is disposed in the mechanical position in which it was designed to act most efficiently. Where the quadriceps attachment to the tibia is maintained or properly substituted, the powerful flexors will have less opportunity of pro- ducing flexion, which, as experience has shown, tends to increase with use. The operative procedures most frequently resorted to are: excision to obtain a false joint (pseudarthrosis); excision to obtain a better position of the limb; osteotomy, breaking the bone after partially cutting it with an osteotome; and osteoclasis, breaking the bone without any cutting. These different procedures have especial advantages in different joints, and can be fully studied and appreciated only under the head- ings of the individual joints. Adolf Lorenz 1 has elaborately considered the con- servative aspect in an article on the " Indications for Arthrodesis and Arthrolysis," the latter term being the one that is now generally accepted as meaning the intentional production of mobility in ankylosis by operative procedure. His conclusions arc that there are only two joints in the body that should be made mobile after ankylosis, viz., the elbow and the jaw. He bases this view upon the fact that there are so few cases that have been operated upon that have re- sulted in permanent restoration of function. The inability to secure a restoration of muscular control often necessitates the employment of varying forms of apparatus to give stability to a joint that has become mobile by operative methods. His belief is that an ankylosed joint in proper position affords higher degrees of efficiency than such joints offer when they are made free, but still lack muscular control. The very many methods of producing mobile joints following ankylosis may be taken as an indication of lack of success of any of them. In some instances a greater number of successful results have been ob- tained than in others. Rhea Barton 2 of Philadelphia in 1826 removed a wedge from an ankylosed hip and instituted passive motions after three weeks, and obtained mobility which, however, became more and more limited, finally ending in recurrence of ankylosis. J. R. Rogers in 1830 attempted the same pro- cedure with equal results. In 1S3S Berard 3 advised section of the condyles after the method of Rhea Barton for temporomaxillary ankylosis. In 1840 J. M. Carnochan' operated on a case of pseudoarthro- sis by division and inserting wool or cotton between the cut ends. In 1853 Schuh freed an ankylosed patella with a chisel, but the adhesion returned. T. Wolff 5 reported nine successful cases following what he terms "arthrolysis," i.e. incision by scalpel and chisel of all the fibrous tissue which hindered movement. Eiselsberg, in two cases in which he employed this was, however, successful in only o and Kocher, while in favor of "arthrolysis," modi it by putting the components of the new joint after "arthrolysis" in a position of dislocation for a week or two, when he reduced the dislocation. Helferich, in 1S99, proposed, but did not carry out, his suggestion of inserting a portion of the vastus internus between the patella and femur to prevent reunion. Cramer 6 reported ten cases of ankylosis of the patella alone, in seven of which the vastus inter- nus was interposed, and six were successful. Chlumsky 7 reasoned from the reports of Mikulicz, Helferich, Leuz, and Riegner, that, notwithstand- ing the good results obtained at times by the inter- position of muscle and fascia, in large joints the procedure, through failure of preservation of the interposed tissues or on account of technical difiienl ties, was not all that could be desired. He therefore conducted a large number of experiments based upon the interposition of such non-absorl:able substances as plates of ceDuloid, zinc, rubber, silver, cambric, and layers of collodion and absorbable material, such as magnesium, ivory, or decalcified bone. In some in- stances there was a tendency to joint formation, but the end results were unsatisfactory on the whole. Mellhenny 5 removed in the inferior maxilla a wedge of bone half an inch wide from the neck of each condyle just above the insertion of the external pterygoid, for temporomaxillary ankylosis, with a successful result. Murphy 9 in October, 1901, interposed flaps of fascia and muscular tissue from the vastus externue between the patella and femur and tibia and femur for an ankylosed knee, with fair result. He reports twelve cases in all, up to January, 1905, some with remarkable result, for the correction of ankylosis of the knee, hip, and elbow, which he accomplished by the interposition of flaps with broad p dieles obtaini d from fascia, fat, and muscle adjacent to the anky- losed joint. His paper is most interesting, extensive, and valuable. Hubscher 10 failed to secure permanent freedom of the patella by the use of the interposition of magne- sium foil half a centimeter thick. Berger 11 successfully used the pronator radii teres between the extremities of the bones sutured to the brachialis anticus for elbow ankylosis, and attributes the satisfactory result to the muscular interposition. Hoffa'- also successfully used muscle flaps. Quenu. 13 in 1902, interposed soft parts after re ection of the elbow for ankylosis. Delbet also praises this method. 452 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES .\no DBS Foderl" after experimental ankylosis produced by resection, produced mobility again by the insertion « »f pj , ces f bladder or the wall ol an ovarian cyst. Baer' 'in 1909 reported three cases in which he had used Cargile membrane between the separated com- ponents of the joints with no resultanf motion, and with fever fur a few days alter the operation. In a fourth case, a knee in which he used Cargile membrane Bn d in which fever occurred, the end result wa 10° lotion, \iiir the method of Foderl, he then also used bladder from the pig, which he had chromicized, this he sutured in the newly separated articulation , the result in the reported cases of 35 motion in a hip, 35° in a knee, 50° in a hip, 75° in a knee; and 100° in the upper radioulnar articulation. The objection to the method seems to be the postoperative fever, trusion of the pieces of bladder through the wound or adjacent tissue at times with resultant formation and suppuration, and in some in- stances return of ankylosis, as reported by Osg 1" and in personal communications from three cases at Si. Agnes' Hospital and Ashbury's observatioi I'lu' advantages claimed by Baer over the bulky muscle Hap and fascia method is that the resultant illation has a in n eh more stable mot ion and there less waddling gait. I in mi' 7 reported a trail nia tie ankylosis of the elbow eleven year old boy. He broughfabout a mobile ! then interposed a free transplanted fascial from the thigh. Systematic mechanical treat- t movements and massage were used, and t welve ths after the operation the elbow had good move- I of 55°. Recently Ilauer of Johns Hopkins Hospital in a case of ankylosed elbow, used a flap i the fascia lata of the patient's thigh with sat- isfactory results. R. Tunstall Taylor 18 presents for consideration the result of his experiments in the introduction of vary- ing formulas of white wax ami lanolin for the produc- tion of mobility ill joints that have been ankylosed. The latter possessing many advantages over the sepa- rating material used by other operators. Taylor's results indicate a successful future for this method. H. Augustus Wilson. References 1. New York Medical Journal, June 22. 1012, page 1301. 2. North American .Medical and .Surgical Journal, 1827, p. 290. 3. Diet, de Medecine, vol. xviii., p. 440, 1838. 4. Lectures on .Surgical Anatomy and Operative Surgery. 5. Berliner Chirurgen Vereinigung, 1895 and 1897. 0. Thirtieth Congress of the Deutsche Gesellschaft fiir Chirurgie, Berlin. April 13, 1901; Archiv fiir klinische t'liirurgie, 1901, Ixiv., p. 696. 7. Centralblatt fiir Chirurgie, Sept. 15, 1900; Wiener klinische Wochenschrift, 19(12-3. s New Orleans Medical Journal, April, 1901. '.» Journal Am. Med. Association. May 27, 1905, p. 1671. in. Correspondcnzblatt fiir Schweizer Aerzte, .Dec. 15, 1901, xwi.. p. 7SY 11. Bull, e.t Mem. de la Soc. de Chir., 1903, xxix. 12. Zeitschrift fiir orthopadische Chirurgie. xvii. ]:; Societe de Chirurgie, Paris, June 25, 1902. 1 1. Ueber Knochen und Knorpelersatz, Wiener klinische Wochenschrift, 1903, xvi, 1424-1429; Jour. Am. Med. Ass'n., 1905, p. 1756 l.">. Amer. Jour. Orth. Surg., August, 1909. 16. Boston Medical and Surgical Journal, July 20, 1911. 17 Zeitschrift fiir Chirurgie, Bd. cviii., H. 3-1. S. 424. is Surgery. Gynecology and Obstetrics, vol. xiv., April, 1912, p. 327. Ankylostomiasis. — See Uncinariasis. Ankvlostomum. — f T urinaria, Dochmius. A genus of nematode worms, family Strongylidoe. A. duodenale lives in the intestine of man. causing severe loss of blood. The eggs develop in mud and moist earth, and enter the body in drinking water or perhaps through the skin. See Nematoda and Uncinariasis. Annatio. Aknotta [Orleana). This coloring mat- ter is obtained from the seed of Bixa OreUana I... a mall tree of South America, belonging I" tin family , ,r. The plant is also cultivated in all tropical countries. Commercial annatto i prepared in a variety of ways, having foi theirobject the eparation from the seed of its coloring matter, and its preserva- tion in a is! or dry condition. The bruised eed is sometimes washed over a ieve and the liquid allowed io stand until the annatto subsides; or it is separated by fermentation. The product i a brownish-red, resinous substance, usually in moist ma se . but sometimes in dry, brittle cakes. It has often little or no. sometimes a sweeti h, re i is odor, ami a saltish- bitter ie-te. Some lots have a very disagreeable smell, and are said by Hager to be prepared with urine. Two kinds are said to lie imported from French Guiana, one without unpleasant smell, the Me. A i inrd variety comes also In. in I. but this is not. so highly esteemed as the be French. Annatto is a mixed substance, nearly insoluble in water, soluble in alcohol, ether, fatly and essential oils, making orange-red solutions. It consists princi- pally of a yellow (firellin) and a red Qrixin) resinous coloring matter. The principal demand for annatto is for dyeing fabric.-,, I. m it is also extensively employed to color butter and cheese. In the tropics it is largely em- ployed tor coloring foods for table use. II. II. RuSBY. Annonaceae. — (The Custard-Apple family.) A fam- ily of nearly fifty genera, pertaining almost wholly to the tropics, of both hemispheres. They yield a number of the most delicious of known fruits, such as those of .1 mama and Duguetia. They are classed near the Magnolias and Myristicas, and, like them, are rich, chiefly in the bark, in volatile oils, for which they are considerably used in domestic practice. H. H. Rusby. Annulata. — An old term used to include the leeches, earthworms, and other segmented worms. A. S. P. Anodynes. — This term (a, privative, and &divq, jiain) is applied synonymously with analgesics (a, and aKywia) to a small class of drugs whose peculiar action is to relieve pain. The anesthetics, which also relieve pain, but by suspending all sensation, together with consciousness and motility, are not anodyne's. By far the most important member of this group is opium (which see). Though other remedies occasion- ally relieve the milder degrees of pain, opium alone can be relied upon to remove severe suffering. It has its limitations, in occasional paroxysms of agony such as attend the passage of renal and gall stones, when nothing short of absolute anesthesia will bring relief. Here opium, in doses so high as-even to endanger the life of the individual, is without effect on the pain. In the ordinary forms of severe pain a failure of opium to give relief is almost always due to improper ad- justment of the dose. Of course, the subsequent ill effects of opium, such as nausea, constipation, and narcotic addiction, may be so marked as to form a contraindication, more or less strong, to its use. Hut. the point here emphasized is that, as an anodyne pure and simple, opium, if properly administered, is almost always successful. In certain subjects, partic- ularly women and nervous persons, the intoxicating effect of opium predominates in the moderate doses. In such cases the dose must be cautiously increased beyond the limits usually prescribed, or else the opium must be combined with some nervous sedative, as bromide of potassium or chloral. For it should 453 Anodynes REFERENCE HANDBOOK OF THE MEDICAL SCIENCES be remembered that opium is, in analgesic doses, by no means always a hypnotic. In many cases in which it completely removes pain, the patient does not close his eyes in sleep the whole night. The common cause of failure in securing the anal- gesic effect of opium is conformity with a strict ami arbitrary posological standard, and forgetfulness of the fact that there is much difference in the capacity of different individuals, and of the same individual at different times, for the drug. Under the influence of severe pain, the toleration for opium increases enor- mously. In general and pelvic peritoneal inflamma- tions, for instance, it may be necessary, in order to get the full effect of opium, to administer it in doses up to four grains (or its equivalent in morphine) at a time, and to repeat with sufficient frequency to keep the patient just short of narcotism. This bold use of opium in pelvic inflammation has come into practice of late years, and some of the figures published of the amounts actually administered are very large. They are not given here, however, for the reason that no definite figures reported in one case should have any weight in determining the amount to be given in an- other case. It is needless to say that, in the case of a patient suffering from a frank peritonitis, which calls for the employment of these heroic doses, and when the individual is held just on the verge of narcotism, with respirations perhaps lowered to ten_ or twelve per minute, no standing order should be given in ad- vance for a stated administration of the drug, and that each dose should be given by the practitioner himself, who should on no account leave the case, and who should have at hand atropine and a faradic battery ready for instant use in case the narcotism goes too far. Among the derivatives of opium, morphine, as an anodyne, stands facile princeps. Its convulsant, constipative, and diaphoretic properties are all less than those of opium, while as an analgesic it is even more active than the drug from which it is derived. Of the other principal alkaloids, the analgesic effect upon man is in the following order: narceine, the- baine, papaverine, and codeine. The interval be- tween the strongest of these and morphine is, however, great, one authority claiming that narceine is four times weaker than morphine, and in practice it is found that none of them can be relied upon with certainty in pain of a severe character. The prompt- ness and effectiveness of morphine as an anodyne are usually enhanced by the hypodermic method of administration. Dionin is an opium derivative use- ful when instilled into the eye in 5-10 per cent. solution. Chloroform is at times an anodyne. This is es- pecially t he case when injected subcutaneous]}' in the vicinity of a nerve, as in sciatica and other forms of neuralgia. Administered by the mouth it also has a local analgesic effect, due partly, no doubt, to its revulsive counterirritant action. It is thus of use in gastralgia and flatulent colic. The spirit of chloro- form, in doses of o i- in hot water, is an eligible form for the internal administration of chloroform, and the Spiritus ^Etheris Compositus, commonly called Hoffmann's anodyne, may be used in the same doses for abdominal pain. The so-called chlorodyne, a British nostrum, has under various modifications been pretty widely used. One of its many formula? is this: Morphina? hydrochloratis gr. viij. Aqua? fl " 3S. Acidi hydrochloriei fl 3ss. Chloroformi fl ."> iss. Tinct. cannabis indicse fl 5i. Acidi hydrocyanici dil. U. 8. P.. . . n\ xij. Alcohol" fl Bss. 01. menth pip n^ ij. Oleoresinse capsici n\ i. The adult dose is from five to ten drops. This may be well replaced in the same dose by the Tinctura Chloroformi et Morphinse, B. P., which was intended to be its official substitute. Belladonna may be considered a feeble anodyne. Administered with opium it has not only a corrigent effect, mitigating some of the unpleasant symptoms of the latter drug, but is also apparently, to a certain extent, an adjuvant. The various coal-tar products, whose name is now legion, have a certain anodyne value. Antipyrine, acetphenetidine, acetanilide, lactophenin, are a few among the many. (See also under Antispasmodics.) Cannabis indica is a still weaker anodyne, if it deserves the name at all. Its hypnotic action can overcome a moderate degree of discomfort, but not much actual pain. It is of some repute in the treat- ment of chronic migraine. There are, besides the foregoing, one or two drugs which deserve mention as local anodynes, although their commoner use is as local anesthetics. For ex- ample, cocaine is chiefly employed to produce an- esthesia, as of the cornea, or by injection to anesthe- tize the field for a circumscribed operation. Its anodyne action may be obtained, however, in con- junctivitis, in painful hemorrhoids, etc. A four-per- cent, solution may be employed. But the ever-pres- ent danger of» establishing the cocaine habit must always be borne in mind before resorting to cocaine as an anodyne. Cocaine itself is much less soluble in water than its salts, e.g. the muriate; but the former is soluble in fats, while the latter are not. Hence in ointments the cocaine itself should be used, and not its salts. Eucaine has been found in many respects a useful substitute for cocaine. Charles F. Withington. Anopheles. — A genus of mosquitos which transmits malaria. No other genus of mosquitos is known to carry this disease. Anopheles is distinguished from Culex, a mosquito often associated with it, by the fact that, though the body is straight, when at rest the anterior end is lower than the posterior; Culex stands with its body nearly parallel to the surface on which it rests and has a distinct bend or hump. A. pun/li- pennis and A. maculipt mi is range nearly all over (he United States; A. crucians is a southern species. See Insects, poisonous. A. S. P. Anophelinae. — The family to which the malarial mosquito belongs. The eggs are laid singly on the surface of the water; the larvae, or "wigglers," when at the surface of the water hold the body parallel with it; and the adults have palpi that are as long, or nearly as long, as the proboscis. See Insects, poisonous. A. S. P. Anoplura. — Lice. Small wingless insects: the head bearing a short tube furnished with hooks; feet terminated by a single long claw. These animals are exclusively blood sucking in their food habits. Man is infested by three species of the genus Pediculus. See Insects, parasitic. A. S. P. Antacids. — See Alkalies. Antenatal Pathology. — See Embryos, Human. Anthelmintics. — Agents rendering harmless or killing worms. A vermifuge is an agent which expels. worms, a vermicide one which kills them, but these terms are occasionally used as synonyms. A priori any agent thus used must cither be in- soluble in the gastrointestinal juices, and therefore non-absorbable, or else, if soluble, must possess the 454 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aflthi'inls faculty of being innocuous to the host at the same time thai it is destructive to the intruder. Drugs of this latter class arc few, and the employment of nearlj all absorbable drugs is distinctly hazardous, for their dose is necessarily large, and they uot infrequently luce various phenomena of poisoning. ,,. convenience worms may be divided into four p , each with its own treatment: tape worms or , ; round worms; hook worms; scat, pin, or thread worms. Tapeworm or Tania. — Drugs used in tins condition arc: male fern, pelletierine and pomegranate from which it is derived, pumpkin seed, thymol, kamala. and numerous others of minor importance. In the treatment of tapeworms the method of cedure is of as much importance as is the choice of edy to be employed. An absolute essential is the withholding of all food from the patient for a twelve to twenty-four hours. If this is imprac- ticable the drug should be administered before break- fast, a light supper only having been partaken of the previous night. About three-quarters of an hour after the administration of the anthelmintic an active e should be administered. Castor oil, from half an ounce upward, appears to be preferred to all other.-., but should not be used with male fern. As desideratum is the removal of the head or heads e ..inn or worms, the stools should be carefully lined for their presence, and in any case a high tal injection should be given, preferably of saline 'ion, as this is most useful in bringing away the head of the taenia, which may be narcotized but not dead. It is of the utmost importance that the bowel discharges be destroyed. (if the agents used against this worm, five are largely and successfully employed, though at times two or even three drugs may have to be successively I. and the treatment may even then fail. Male fern (aspidium) is most useful in the form of the oleoresin, given in four capsules of fifteen minims each, at one dose, or in two doses half an hour apart in combination with calomel. Pepo is most effective and may be used by taking two ounces of the pow- dered pumpkin seeds to make an emulsion or a con- fection, this amount being the usual dose. Thymol is one of the most available remedies, and may con- veniently be given in capsules of ten grains each, one ule being taken every quarter of an hour until two drams are taken. Alcoholic beverages should be avoided when thymol is used. Pomegranate is used by taking two ounces of the bark, adding this to two pints of water which is boiled down to one pint, and of this a wineglassful is taken ever}' half-hour; and it> alkaloid, pelletierine, in the form of the tannate, may also be used in three-grain doses. Kamala is by Brumpt to be insipid and therefore very well suited to children, but inert in adults. It sometimes produces gastroenteric irritation. Dose, half to one gram for each year. All other teniacides are either inferior to the preceding or dangerous (chloro- form, turpentine). Children under two years of age react badly to teniacides as a rule, and great care must be taken in treating them for this condition. Round Worm or Ascaris Lumbricoides. — These worms affect children rather more than adults, and infest the upper part of the small intestine, though rarely they work their way up into the stomach, and n into the esophagus and pharynx. Santonin, the active principle of santonica, is regarded as a true ific vermicide for round worms, and when given with castor oil (5ss) in doses of gr. £ (0.01) for each year of the child's age it should occasion no toxic symptoms. The adult dose should not exceed gr. iii. (0.2). To augment its action thymol or calo- mel may also be given. The older drugs like worm- seed and pink root hardly have any special field of usefulness, being less certain of action. [n treating any patient for the presence of a caride . it is in ce ary, as in the case of tapeworm, that food lie abstained from for twelve or, better, twenty-four hours; that an active puree be administered about three-quarters of an hour after the re ly ha been taken; and that the bowel discharges be destroyed. Haul: Worms. — The parasitism of Necator ameri- cantlS or hook worm, and il - closely related congi Ankylostomum duodenale, with the disease which I hey produce is naturally eon idered in full elsewhere. From the therapeutic standpoint thee intestinal parasites are amenable to vermicides like the preced- ing. As in the case of the teniae th mo I efficacious arc male fern and thymol. In the mines where anky- lostomiasis prevails, male fern (oleoresin) is freely combined with both castor oil and chloroform, all in full doses, very energetic treatment being necessitated. In the uncinariasis of the United States thymol is given in full doses of the powdered drug. Oils, alco- hol, or other solvent substances must be avoided during the treatment lest fatal poisoning results. Water is of course permissible. With this precaution the drug may be given hourly on the fasting stomach in fractional doses, the full amount not to exceed 150 grains (10.0). The number of other substances having some power over the hook worm is large. It comprises oil of wintergreen, oil of eucalyptus, /3-naphthol, etc. Seat, Pin, or Thread Worms; Oxyuris Vermic- \daris. — These worms generally infest the rectum and colon, and are most common in children. Anthel- mintics used against the tape and round worm can be employed, as many of them are equally destructive to the seat worm. The only rational procedure, in fact, is to attack the worm from above. Thymol, santonin, and calomel are all eligible, given as in the case of round worms and tapeworms. In regard to local injection treatment there is no good reason for the belief that infusion of quassia, that time honored empirical remedy, is superior to in- fusions of wormwood or tansy; or that these vegetable bitter infusions are superior (when internal treat- ment is used) to simple clysters of oil, glycerin, and water or saline infusion. If a parasiticide is indicated there is nothing superior to an injection of infusion of santonin itself. Before using this or any other injec- tion the bowel should be thoroughly cleansed with soap and water, and it is imperative that the injec- tion be retained, by pressure over the anus, for fifteen or twenty minutes, and that the region around the anus be thoroughly washed with salt and water. Failure to observe these precautions will render the treatment of little avail. For cleansing with soap and water and for injecting the medicament a soft rubber catheter or rectal tube will be found most useful in aiding the solution to go well up into the colon, and it is advisable to repeat the treatment two or three times at intervals of a day or so. Charles Adams Holder. Edward Preble. Anthetnis. — Chamomile; Roman, English, or Garden Chamomile. "The dried flower-heads of Anthemis nobilis L. (fam. Compositie), collected from cultivated plants" (U. S. P.). In this definition the Pharma- copoeia recognizes the fact that under cultivation the aroma and flavor of the chamomile grow finer and less rank and heavy, notwithstanding that the percentage of volatile oil, and very likely the medicinal strength, are somewhat decreased. The chamomile plant is a native of Europe and is largely cultivated in temperate regions. It is a low perennial, hairy herb with a branching rhizome, and rather numerous stems, most of which are short and bear leaves only. The flowering stems are long, slender, prostrate, often rooting at the base, but ascending and branched above, and bearing the flowers at the ends of the branches. Flower-neads 455 Antliemls REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 254. — Chamomile, "Wild or Single-Flowered Plant. One-third natural size. (Baillon.) radiate, about two centimeters (f in.) across with, in the "single" (natural) form, a single row of white rays and a yellow disk. Involucre of two or three rows of blunt, appressed, scarious-margined .scales. Receptacle chaffy, conical, solid, longer than broad; ray flowers fertile, limb three-toothed; disk flowers perfect, tubular below, bell-shaped above. Achenia obovate, slightly compressed, pappus none. The oil glands are mostly on the corolla tubes, and less abundant on the ray than on the disk flowers. Un- der cultivation, ligulate flowers largely replace the tubular disk flowers, so that the heads become "double" and large and white, which condition, by careful and rapid drying, should be preserved in the dried heads. Chamomile contains nearly one per cent, of a blue volatile oil, turning greenish or yellow- ish with keeping and having a specific gravity of .905 to .915. The important constituents of this oil are anthemol (C, H 1(i O) and cumin aldehyde (<',II 4 .C 3 - Hj.CHO). The composition of the remainder of the oil is very complex. With the oil there are an amaroid, some resin, and a little tannin. Chamomile is one of the very best of the aromatic bit- ters, and is strongly carmina- tive and somewhat antispas- modic. The dose is gr. xv.-lx. (1.0-4.0). There is no official preparation. The best form of administration is a tincture, so as to contain all the oil. As a simple stomachic a decoction or infusion is excellent. This should be well diluted, taken slowly before meals, and the dose should be small. The oil is often given as a carminative and antispasmodic, in doses of iro i. to v. (0.00-0.3). Allied Plants. — The genus contains about eighty species, and includes the common mayweed (Anthemis cotula Linn.). They are generally less agreeable than chamomile, and although of simiar qualities, not in use. Chrysanthemum parthenium Pers. (feverfew) is sometimes used as a substitute or adulterant of this article. It can be told by its flatter and less chaffy receptacles. Henry II. Rusby. Anthracosis. — The deposit of fine particles of carbon in the body tissues is known as anthracosis. Carbon, either in the form of soot from smoke or dust from unburned coal, is one of the most common forms of dust, and under the ordinary conditions of civilized life is almost constantly present in the atmosphere. It may gain entrance to the tissues either through the respiratory tract or through the alimentary canal. The inhalation origin of anthracosis has been accepted without question until recently when, through the investigations of Calmette, Guerin, Van Steenberghe, and Grysez, the opinion has gained ground in France that the deposits of carbon dust in the lungs and bronchial glands are the results of ingestion and not of inhalation. Experiments on rabbits showed that ligature of the esophagus prevented anthracosis; while, when swallowing was permitted in animals having one bronchus plugged with cotton-wool, the corresponding lung developed anthracosis in the same degree as the other lung. Repeated experiments by the investigators named have shown that finely powdered coal dust, cinnabar, and India ink may pass the intestinal wall into the lymphatic system and thence into the lungs and bronchial glands. The intestinal epithelium apparently plays no part in the transmission of the dust particles; it is accomplished chiefly or wholly by the leucocytes. In young animals the pigment thus taken in through the intestinal mucosa is largely filtered out by the mesen- teric glands, but in older animals a larger port ion of the dust or pigment particles passes on through the thoracic duct and thence into the lungs. Feeding experiments show that pulmonary anthracosis may develop rapidly in this way. Calmette argues, therefore, that physiological anthracosis is chiefly due to an ingestion of carbon dust. Only after a pro- longed stay in a very smoky atmosphere does inhala- tion play an important role in the production of this condition. Biondi has confirmed Calmette's statements in so far as experiments with powdered graphite are con- cerned, but points out that metallic dust acts in a very different way from carbon dust. When ingested the former is dissolved or chemically changed and is nol deposited in the lungs or bronchial glands, so that deposits of metallic dust occurring in the lungs i be the result of inhalation. Petit has also confirm. 1 Calmette's views by the feeding of charcoal dust to infants suffering from fatal conditions such as tuber- culosis and marasmus. To prevent the entrance of any of the dust into the respiratory tract it was given in a suspension through an esophageal tube. At autopsy the mesenteric glands, lungs, and bronchial glands of the tuberculous infants showed anthracosis, but it was absent in the glands of the marasmic infants. In Germany the work of the French observers has been generally discredited, and the German patholo- gists have not accepted Calmette's views. Schultze found in feeding experiments carried out upon guinea-pigs and rabbits that deposits of the pigment were present only in the intestine and lung, and regards this as evidence that some of the carbon dust had been inhaled accidentally. Aschoff's experi- ments with the feeding of carmine were negative. Miranescu in a series of feeding experiments with India ink, carmine, and charcoal emulsion obtained no pulmonary deposits as the result of ingestion alone. Likewise the feeding experiments conducted by Feliziani proved negative. On the other hand, inhala- tion experiments carried out by various workers upon the guinea-pig, rabbit, and dog show that inhaled carbon dust can penetrate the lungs and after entering the lymphatics pass to the bronchial glands. In this undecided state the matter stands at the present time, and a thorough investigation of the whole subject of anthracosis seems necessary in order to settle this and the other important questions arising out of Calmette's claims. If the ingestion theory of anthracosis is shown to be correct, it would appear not at all improbable that many of the inflammatory affections of the lung, as well as tuberculosis, are the result of infection by way of the intestinal tract. Other recent contributions to our knowledge of anthracosis deal with its relation to tuberculosis. Among these may be mentioned Ribbert's view that anthracosis is largely determined by a previous healed tuberculosis, although he rejects wholly the ingestion theory. Wainwright in a study of the miners of the anthracite region in Pennsylvania found the death rate from tuberculosis among them to he only 3.37 per cent, for adults as opposed to 9.97 per cent, in all other occupations. Wainwright and Nichols have also carried out experimental investiga- tions to determine if pulmonary anthracosis rendered the lungs less susceptible to tuberculosis, as has been claimed in the case with miners. Two sets of guinea- pigs were given intratracheal injections of tubercle bacilli. One set had been kept for two months in an atmosphere saturated with coal dust. In this group 456 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anthrax of animals the lungs remained practically free, although abdominal tuberculosis developed. The control group developed pulmonary lesi 3. No satisfactory explanation of this phenomenon wa discovered, bul il was thought thai the soluble all f |ime contained in coal raighl have an inhibiting ,n upon the growth of tubercle bacilli, or thai . ., i,, changes occur in the structure of the lungs that render them less susceptible to infection. On the other hand, marked anthracosis of the lung 1 often associated with a chronic fibroid tuberculosis. Avnn; u osi ~ l' rl M " sl M - "The lungs of the arc grayish-pink wil ;ment, but in a very ler ordinarj condit ions deposits of blai pigment appear in spots over the surface of the ■ \. a rule it i not well marked before the .,. bul may be - arly as the third or fourth month after birth. It increases with age and ording to the conditions of life of the individual .,,..,, engineers, coal-miners, dwellers in smoky :.). Only a very small portion of the carbon tied cains entrance to the tissues, the greater g thrown out in the exhaled air, in mucu tic cells, aided by the cilia of the respiratory epithelium. Desquamated epithelial cells and 1> ntaining carbon pigment are always presenl in the alveoli. In early stages of anthracosis the lungs 1 >ver with small black granules on the surface, often arranged regularly about the lobules. In more advanced cases the pleural surfaces of the lungs may -how heavily pigmented bands corre- iding to the intercostal spaces, while the portions urface corresponding to the ribs are less : pigmented. The posterior and middle por- e usually chiefly affected, although occasion- ally the apices show it. The parietal pleura may be ilarly marked in black bars or stripes. Small flattened black nodules are often seen in or beneath the visceral pleura. They are hard and dense, and often calcified. For the greater part they repre- healed tubercles; in these the pigment shows an cial tendency to collect. Microscopically the nent is found chiefly in the primitive lymph nodes along the course of the lymphatics in the peri- bronchial connective tissue, interlobular septa. 1 walls of the arteries. The bronchial nodes arc heavily pigmented. In the ordinary physiological ■ the anthracosis does not extend beyond the bronchial nodes, and no ill effects result. In the more marked cases (coal-miner's lung) the lungs may be slaty and black throughout, and either are diffusely indurated (anthracotic induration) or present nodular areas of black induration. Softening of the latter may occur, leading to the formation of ities filled with a black granular material {phthisis a). This softening may be non-bacterial in origin, 1 should not be regarded as tuberculous without microscopical examination. On microscopical exami- nation the advanced case of anthracosis shows usually chronic bronchopneumonia and induration erstitial pneumonia). The epithelium of the iles and alveoli is granular, pigmented, and quamating. The loss of the epithelium increases the tendency for the pigment to gain direct entrance into the capillaries. Chronic adhesive pleuritis is usually present also. The bronchial glands are black and indurated, but softening (suppuration, tuber- culosis) is not uncommon and the softened node may break through into the blood-vessels, bronchi, or trachea. The pigment may then be carried to spleen, liver, kidneys, etc. Even without such a rupture into the vessels, pigment may be found in these organs in severe cases of anthracosis, so that a direct passage of carbon granules from the pulmonary alveoli into the capillaries must be regarded as possible. In severe anthracosis the lymph nodes of the mediastinum, cervical and retroperitoneal regions may become anthracotic. In the ca e ol the abdominal lymph nodes the anthracosis may be the re nil of a retro- grade metastasis. From the softened bronchial nodes the pigmenl ma} be carried into the walls of the trachea, bronchi, bl [-vessels, and esophagus, u ually after tdhi to these si rucl urea have occurred as the resull of a periadeniti . Ei n and perforation may lead to the establishment of com- munications between esophagus and bronchus with resulting moisl gangrene of the hum. Indurated anthracotic bronchial nodes may al I tion- dh erticula of t he i ophagus. Anthracosis of the Spleen. — Following the rupture of a softened or tuberculoid I hial node into the bl l-ve i I (pulmi mai j ' ein pari ii le of carbon enter the arterial circulation, and tire carried to the various organs where they lodge first upon the helium. They are then passed into t he I ic phagocytic cells so thai within a relatiyelj hort time the pigmenl disappears from the circulation. In the spleen it is cull, ■del around the trabei : the adventitia of the arterie , and follicles. _ Pign lies may til-" be found in the endotheliui splenic veins. To the naked eye the pigment appears as small black points, scattered over the cut surface, but in very severe cases the spleen may be slate colored and indurated. A moderate degree of anthra- cosis of the -pleen is not uncommon in old people, particularly those with emphysema, and who live in a smoky place. It is probable, therefore, thai the pigment can pass directly into the _ pulmonary capillaries, and thence into the systemic circulation. Anthracosis of the Liver. — Carbon gains en- trance to the liver under the same conditions as jn the case of the spleen. The pigment is found first in the endothelial cells of the liver capillaries, and then col- lect s about the central vein and the periacinous tissue, particularly in rudimentary lymph nodes. To the naked eye it may appear as small black dots beneath the capsule or on the surface. The portal glands may be slaty or black. In very severe ca the interlobular connective tissue may become in- creased (anthracotic cirrhosis); or the deposit of the pigment is coincident with a cirrhosis. Anthracosis op the Kidneys. — This occurs under the same conditions as anthracosis of the spleen and liver, but is more rare, and is usually less marked. The pigment is found about the larger blood-vessels. Anthracosis of the bone-marrow, tonsils, and prr- iphi ral lymph nodes has also been observed in cases in wdiich a large amount of carbon has gained entrance to the circulation through the rupture of a softened bronchial gland into a pulmonary vein. In the case of tuberculous softening of these glands a metastasis of tubercle bacilli may occur at the same time as that of the pigment. Aldred Scott 'Warthix. Anthrax. — Synonyms: Carbunculus contagiosus; Milzbrand; Charbon; Wool-sorter's disease; Mai de rate; Mycosis intestinalis; Anthracemia; Malignant pustule; Splenic fever. (See also Carbuncle and Furuncle.) A specific, highly infectious disease, common to most vertebrate animals and communicable to man (though in varying degree). The disease is not con- tagious in the ordinary sense of the word, but it is in a high degree transmissible by means of secondary media of infection. It maintains its virulence for long periods, and suffers no deterioration from trans- portation or variations of climate or other external conditions. It appears as an acute intoxication, usually of a restricted part of the body, but later of the entire body, and is due to the invasion of the tissues of its host by the Bacillus anthracis. The disease is primary in animals, and occurs in the hu- 457 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES man subject in two distinct forms, viz., by direct inoculation, or indirectly by eating the flesh of ani- mals infected with anthrax or by inhaling dust which is contaminated with the poison of anthrax, as in the operations of currying hides, upholstery, mattress- making, etc. The blood, tissues, and excretions of an animal dead from anthrax are found to contain a minute organism, in the form of a rod bacillus, which has been demonstrated to be the specific and invariable cause of the disease, and may be obtained in every fully developed case of anthrax. At the point of invasion the bacillus first acts as a purely local poison, producing only a local irritation, but, it soon multiplies rapidly, and later is conveyed by the circulating blood into all parts of the body, where by its enormous numbers it blocks the capillaries with embolic masses of bacilli, causing innumerable hemorrhages into the organs and tissues, and effu- sions into the serous cavities and cellular structures; and by its specific toxin acting upon the sympathetic nerve centers it produces great depression of the vital functions, which often ends in death within a few days. Koch first demonstrated that the development of anthrax is inseparably associated with the life and development of the Bacillus anthracis, and that only infected substances which contain bacilli capable of growth and development, or the spores of the anthrax bacillus, are able to produce the disease; and that the propagation of pure cultures of Bacillus anthracis, obtained from actual cases of the disease in animals, through more than a hundred generations by trans- plantation to fresh media, does not change the nature of the infection; but that material from the last experimental transplantation possesses the power to produce anthrax just as certainly and in as typical form as the original material which was obtained from the diseased animal. Anthrax is the most widely spread and the most de- structive of all communicable diseases which affect ani- mals. The malady is primary in the herbivora, and is found in all countries. It is very prevalent in parts of France, Germany, Italy, Persia, North and South Africa, and South America. It is least prevalent, though not absent, in Australia, North America, and the British Isles. Epidemics of the disease often appear among cattle and sheep of affected regions, ami may be fatal at the rate of from fifty to seventy per cent, of the animals attacked. It also attacks human beings in infected districts by inoculation from the lower animals, and is often attended with great fa- tality. All classes of vertebrate mammals are sus- ceptible to anthrax. The disposition of the mam- malia to anthrax may be expressed in this ratio: herbivora, omnivora, carnivora — the first having the greater, the last scarcely any susceptibility under natural conditions. Both omnivora and carnivora appear to be absolutely immune to local infection, even when living in notoriously infected districts, frequently drinking the same water, and roaming over the same territory in which herbivora may have been infected, and are dying at the time. There is no other source for anthrax in man than direct contact with a diseased animal, or indirect acquisition through some product of a diseased or dead animal. Of two hundred persons who ate of the cooked flesh of a diseased ox, not one became diseased; while five who handled the fresh meat became diseased and three died. Whatever the anthrax toxin may be, it certainly is either not dan- gerous to man if taken into the stomach, or is de- stroyed in the pickling and cooking of the flesh. The disease does not spread by contact or associa- tion; it can be acquired only by the introduction of the infective organisms into the body, either through an abrasion of the skin or a defect in the mucous membranes, or by the spores of the bacilli finding their way through the epithelial lining of the alimen- tary canal or respiratory tract, and so causing gen- eral infection. The inoculation of these organisms produces the same fatal effect upon animals as does the infection from the original source of the primary disease. Blood taken from a diseased animal is also fatal if introduced into the tissues of another susceptible healthy animal; but if the blood is filtered previous to its introduction, so as to remove all germ-, it is no longer infectious to a healthy animal (Klebs, Pasteur). In Great Britain, anthrax is included among the maladies specified under "The Contagious Diseases Acts." In England, numerous outbreaks of anthrax have been traced to the refuse of washings from wool, hair, etc., which are discharged into streams or sewers, and from the solid residue which is used for manure. Animals rarely take the disease from other animals, but obtain it indirectly from the soil or other second- ary medium of infection. Thus, certain restricted re- gions or localities become centers of infection where the disease shows itself year after year. This may arise from the superficial burial of animals dead from anthrax, which leads to the infection of the soil, which, once produced, is not easily eradicated. In portions of the province of Brandenburg, the owners of cattle have learned by oft-repeated experience the exact boundaries of limited districts, and even of certain fields, where anthrax contamination persists in the soil. The same condition prevails in certain portions of the Bavarian Alps. No ordinary changes of temperature, such as freez- ing of the ground, affect the vitality of the organism. Stable implements, veterinary surgical instruments, etc., may spread the disease among healthy animals. The bodies of animals when buried are not so dan- gerous for the propagation of anthrax as are the blood, intestinal contents, etc., which may be scattered on the surface of the ground or adhere to gra-s shrubs, etc. Herbivorous animals, such as cattle and sheep, are more susceptible to the intestinal form of anthrax, but are less often affected by the external form of the disease, the so-called " malignant pustule."* Others, such as guinea-pigs and rabbits and white mice, are less often attacked by the intestinal forms, but are more susceptible to subcutaneous inoculation by experiment. The carnivora are less susceptible than other classes. Animals ordinarily acquire anthrax by way of the intestinal canal, through infected fodder, stable litter, manure, or from water polluted by an- thrax infection; or from infection of the pastures or fields ow-ing to the exposed bodies of animals dead from the disease; or from the contamination of the grass by the anthrax germs from the dead body of an animal which has been buried in the vicinity. Direct inoculation of anthrax in man is not very com- mon. It can happen only in those whose calling brings them in direct or personal contact with the diseased or dead animal. There must be also either an abrasion of the epidermis or a wound of the skin to insure infection. Veterinaries and knackers have been more frequently affected than physicians, nurses, undertakers, or butchers. Herley (the Lancet, Dec. 4, 1909, p. 1664) reports a case of anthrax in a butcher, one of whose cows had suddenly died; he skinned and cut up the carcass the same day. The meat was sold to his neighbors, and the hide to a dealer. Ten days later the butcher was admitted to the hospital with a typical anthrax "pustule" on the front of the left forearm, where he had received a scratch while skin- ning the dead cow. The whole of the limb was swollen, and there were several bulla? on the fore- * "The name 'malignant pustule* is a misnomer, as it does not contain pus; and when it remains the only manifestation of the disease, is not particularly malignant" (Bryanl and Buck). "Suppuration does not occur unless there is a mixed infect (Keen). 458 i;i:i u;i:\ri. n wdkook or i in: mkdical sen mis Anthrax nnii. Temperature was in:; , pulse 92, and respira- tions 24. This patient nil imalely recovered after a very severe illness. The flesh of the cow, as stated, was snlil tn " neighbors" at reduced prices, ami prob- ably over inn persons partook of it. One woman who handled the raw meal developed a malignant pustule mi her face; but no ea se (if iiite-l inal ant hra \ was recorded. A second cow in the same herd con- tracted anthrax and died, bul was cremated in the orthodox fashion. There is danger in man from Hies about those affected with anthrax, as it has been ived that the virus of many infectious diseases may ved by insects, either from soiling of their bodies or limbs with the infectious material, or from their dejections which may contain the germs of an infectious disease. Anthrax in man, in this country at least, is almost, exclusively limited to those working in animal products imported from other countries where I he disease exists. The dead animal is far more dan- us when thus distributed than is the living animal to the human beings in its own immediate vicinity. Infection may occur through the skin. the intestines, or the lungs. In a guinea-pig a single Nils of virulent anthrax: is capable of producing fatal infection. In infected localities the anthrax bacillus lives in the soil, and may thus render certain portions of a field or pasture where the bodies of animals dead from the disease have been buried a permanent source of the disease to other susceptible animals through long periods. The greatest source of danger in this disease lies in the fait that the virus may be introduced through the smallest abrasion or injury of the skin or of the mucous membrane of the alimentary canal. The degree of susceptibility of different animals to the poison of anthrax is not uniform. Strong, healthy animals are more easily affected than the lean or sickly. One attack affords no protection against a recurrence of the disease. To show the ravages of this disease, it may be stated that in Russia, in the year 1804, no less than 72,000 horses were destroyed by it. In the province of Novgorod, within four years, more than 56,000 horses, cows, and sheep, as well as 525 men, fell victims to this terrible - 'nirge. Statistics for the years 1901-1903 show that about 150,000 cases of anthrax were reported in European Russia and the Caucasus, and about 1,500 in Ger- many, and 12,000 in Italy. The source of infection from horsehair could be traced to that brought from China. Russia, Siberia or South America. In hides and skins, those imported from China, Bombay, and t lie East Indies were the most common carriers of lion. In 1899, Russell traced cases occurring in Wisconsin to hides received from South America and China; while Revenal in 1897, attributed twelve fatal eases in man, and sixty in cattle to Chinese hides. That material imported from these countries is par- ticularly liable to contain anthrax infection is due to climatic conditions; "Places liable to be flooded, and drying out to a considerable degree in summer, characterize districts in Persia, Asia Minor, and the plateaus of Central Asia" (Billings). Willard col- lected ten cases near Philadelphia, with a mortality of fifty per cent. The months of July and August witness the greatest number of cases, when the soil contains much putrefying organic matter believed to favor the growth of the organism. Males are af- fected far more frequently than females; ninety-six per cent, of 261 cases collected by Legge in Great Britain being males. (Keen's Surgery, vol. i., 1906.) There are three portals of entry, corresponding to the three clinical types of the disease: when the organisms are (1) deposited in wounds or abrasions of the skin; (2) are inspired; and (3) when they- are ingested into the gastrointestinal tract. In Legge's oases, six only were of the internal variety; the remainder occurred in eighty-five per cent, upon the head, face, and neck. In 923. cases collected bj Koch (1886), mo i of which were contracted from hides and skins, the head and face were affected in forty- eight per een!., a n.l I he 1 1| i| ier e\l remit y, particularly I In hand and lingers, in forty per cent. The disease spreads among men in proportion as they are exposed to infection from diseased animals or men.* Shepherds, farmers, butcher-, coach lie n, stablemen, as well as veterinary surgeons and tho 6 individuals who handle animal products, such as wool sorters, curriers, mattress-makers, etc., are especially exposed. Horsehair is particularly dan- gerous. Further, articles like hid.-, horns, wool, eie., from countries where i he disease is prevalent, which may be transported great distances, are liable to convey I he infection and Ihus give rise to the mal- ady among those employed in their transportation or manufacture. Trousseau mentions two factories in Paris, in which horsehair from Buenos Avres was used in upholstering furniture, and in which not, more than six or eight workmen were employed: during ten years twenty laborers died in these estab- lishments from anthrax. Even after the hair has been long in use, the disease may be induced in the form of true malignant pustule in those employed in renovating the upholstering. A small scratch or crack in the skin or mucous membrane is sufficient for inoculation, and frequently the disease is intro- duced into the system by the unclean nails or fingers of workmen in scratching the face or arms. At an inquest held recently at St. Pancras on the body of Henry Stephen Thurston, laboratory at- tendant at University College Hospital, it was proved that the deceased had died from anthrax poisoning. He had developed a boil on the side of his neck which had been removed after microscopic examination of matter from it had shown that it was due to anthrax. After the operation he had progressed so favorably as to appear out of danger, but a rise of temperature followed and he died several days after the opera- tion. The actual source of infection was obscure. Dr. Francis Thiele, lecturer on bacteriology at the hospital, stated that experiments in connection with anthrax had been conducted in the laboratory, and explained to the jury the possibility of a tube having been left out in error, in which case it might have been handled by the deceased. If this happened, the tube might have been in a condition to require sterilization outside, and it, would, in fact, have been sterilized if the attendant had reported having found it. As he had suffered from toothache, he might have touched his face and neck and infected the latter through a scratch. The jury returned a verdict of "death by misadventure." (The Lancet, July 22, 1911, p. 272.) The deputy coroner recently held an inquiry into the death of a workman in the Mersey Docks and Harbor Board's wool warehouse, which occurred at the David Lewis Northern Hospital on Dec. 2. The deceased had been employed at the warehouse for the last ten years. His duties were to deal with bales of Persian wool, which had been imported into Liverpool by a ship from Bombay. Shortly after 6 p.m. on Nov. 29, he drew his landlady's attention to a pimple on his neck, and said to her, "That's anthrax. He went to the hospital, where the lesion was dressed, and returned home. He returned *"An extensive outbreak of anthrax among cattle has been discovered on the East Kami, which has evidently been in progress for some time. This disease is always specially dangerous in South Africa, as most natives will feed readily on the half-cooked flesh of animals dead from disease. A large number of cattle are officially reported to have died from the disease already, and one adult native. It is probable, however, that there have been other deaths which have not been recorded. The Agricultural Depart- ment has taken up the matter and has imposed stringent quarantine over the area. It was, however, uncommonly slow in acting in the first instance." — The Lancet, March 9, 1912. 459 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES to the hospital on the following day and was advised to heroine an in-patient, where an operation was subsequently performed. In spite of this he died on the following day. A verdict of death from "anthrax poisoning" was returned by the jury. [The Lancet, December 16, 1911, p. 1741.') Ih. disease may be spread from man to man. The discharge from the pustule (anthrax carbuncle) contains the bacilli of the disease, and its inoculation will be followed by the development of anthrax. Repeated transmissions of virus do not cause a dimi- nution of virulence: the last generation is as highly infectious as the first. Anthrax is observed in men in the proportion of fifty-nine per cent., to forty-one per cent, in women. The seat of the primary sore, the malignant pustule, was found by Virchow to be confined to the face, hands, fingers, forearm, or neck in eighty-four per cent, of cases. In the rest, sixteen per cent., the arms and lower extremities were the seat of infection, and in these cases the patients were chiefly women and children, in whom these regions are more exposed than in men. There is a varying susceptibility to anthrax among different families of the same race. This has been observed in both men and animals. Thus the negro is less susceptible than the white man, and certain breeds of sheep, notably the Algerian variety, are less susceptible than are other breeds. Deer, reindeer, and elephants are also liable to the disease. The bacillus of anthrax is famous as being the first microorganism to be discovered as the actual cause of an infective disease. " The bacilli of anthrax can live only a relatively brief time; but the spores have unusual tenacity of existence. They may remain dried up for year-. and then be brought to further development if placed in favorable conditions of heat and moisture. If the spores are transferred to animals, they develop into bacilli, and there is scarcely room to doubt that men and animals are quite as often infected by spores as by full-grown bacilli. There are facts which render it nut impossible that the anthrax bacilli may exist in other places than the bodies of men or animals, and may there complete their cycle of development. Such places are marshes, the banks of streams, and the like. If it is possible for them to be carried by high water to the pasture lands, we have an ex- planation of those sudden endemic appearances of anthrax which sometimes occur in places pre- viously free from the disease." (Struempell, ''Text- book of Medicine," translated by Vickery and Knapp, 1912, Vol. i, p. 15S.) The infection with anthrax in man is little common in comparison with its ravages in certain animals. In the years 1S93-1S99 in Germany, according to statistics, 604 human beings were infected with anthrax, with ninety-six deaths; while 29,686 animals were attacked with the disease. Even in "anthrax districts" this disease occurs only in single occasional cases, and never in the form of an extensive pestilence. A partial explanation of the relative exemption of human beings is an apparently lessened disposition to the disease in the human subject than in cattle, as the human anthrax in the great majority of cases recovers, while this disease in animals gives only a small percentage of recovery. In Santo Domingo in 1770 it was the cause of the death of 15,000 persons in the space of six weeks from eating the flesh of animals dead from the disease. Other observers in mostly tropical countries report as low as twelve per cent, or even five per cent, mortality. Such a statement should, however, be taken with some amount of reservation. In forty- eight cases of external anthrax treated at Guy's Hospital in London, thirty-nine recovered after operation for the destruction of the local disease. The infection of a wound of entrance by the poison cannot be prevented by the immediate irrigation 460 of the wound by corrosive sublimate or carbolic acid if the bacilli have once gained entrance into the flesh. The disease is by no means always fatal to animals. Fagge states the average mortality among horses and horned cattle to be seventy per cent. Clinical Course. — External Anthrax. — During the first day the seat of infection is more or less irritable, sometimes painful. The continued itch of the part, with augmentation of the redness, an edematous swelling, together with shooting pains in the locality, with red lines beneath the skin, marking the course of the swollen lymphatics, are among the strongest initial symptoms of anthrax. As the disease progresses, these conditions increase in inter it.y, and the tissues about the point of infection become discolored and variegated in tint. The formation of a vesicle at the point of infection, with subsequent rupture, and the appearance of a crust or seal, decidedly characteristic, lever is often pre even at this stage, though it may not be observable in the early stages. Diarrhea is frequent. Malig- nant cases may terminate fatally in from twenty- four to forty-eight hours, often preceded by colla] During the second day there usually* app. vesicle varying in size from one to three centi- meters with a yellowish or brownish exudation. At about the third day, the vesicle bursts and shrinks, leaving a brownish base, exuding serum. On the fourth day there is a black, dry. depressed crust or scab, often called the eschar, which is surrounded with a very characteristic, slightly elevated bolder or wreath of small new vesicles. There may be other discrete or confluent vesicles in the neighborhood. Pus is first observed at the end of the tenth or fif- teenth day, if the patient lives so long, when the separation of the sloughing eschar, accompanied with suppuration, occurs in the usual manner. There is then usually a mixed infection. The initial symptoms of anthrax are similar to those of other acute febrile diseases: weakness, ma- laise, chilliness or moderate rigor, headache, thirst, restlessness with or without mild delirium, some- times vomiting, and disturbed sleep. The subse- quent symptoms vary in character and intensity according to the external localization of the disease. If this is in the stomach, there may be obstinate vomiting; if in the intestine, persistent diarrhea; if in the pulmonary structures, rapid breathing, with symptoms similar to those of extensive pneumonia, cyanosis, and speedy collapse. Serious disturbance of the brain may be associated with any of these conditions, accompanied with convulsions and coma. The temperature curve is similar to that in other acutely toxic febrile conditions, ranging from 102° to 105° F. Dr. Hamer reported a mortality of forty per cent, in eases of anthrax of the neck, while the mortality in cases in which the primary lesion was situated upon other parts of the body was twelve per cent. Anthrax is less fatal in tropical countries, where the condition of the climate, heat, sunshine, etc., may produce diminished virulency of the specific organism of the disease. Perhaps a greater resistance to the effect of the bacilli, or of their toxins, on the part ol the inhabitants, or a greater toleration of the infective poison, may account for the less fatal character of the malady in those regions where the mortality has been reported as extremely low, varying from zero to one per cent. A pronounced systemic reaction with much local inflammation has been thought favorable to recovery. In asthenic conditions of the system the prognosis is less hopeful. The pulse, respiration, and tem- perature are not always indicative of the gravity of the disease or of the probable result. Dr. Bell gives the following table of mortality in relation to the duration of the disease: REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anthrax 2d :i,l Ith 5th 6th 7ih - 1! 1 I r nine days, 1 case; total, 55 cases. Internal Anthrax. — Fur convenience of description anil clinical study, this type of the disease is divided into intestinal anthrax and pulmonary anthrax, or wool-sorters, disease. inal Anthrax (Myco I "alis). — In some oases tin- primary lesion of anthrax, the main En-nil^', is seated upon the internal surface of the id produces the symptoms known as those rycosis intestinalis, followed by the same train of fatal results as when the primary lesion is upon the external surface. Often the milk and the flesh of diseased animals are taken as food, and doubtless the infection frequently occurs from this source. The course and symptoms of this form of the disease are not well understood. Often the workmen engaged in slaughtering diseased animals become infected by direct inoculation, while those eating the flesh of the same animals experience no harm. It is probable that the bacilli are destroyed bytheproi of cooking, which generally require an elevation of temperature sufficient for their sterilization; or pos- sibly they may be rendered harmless by the gastric digestion: but if they succeed in passing the stomach, they may then become seated in the mucous mem- brane of the bowel and there produce the disease. Intestinal anthrax is rare in man, though it has bee ally reported. (For a most intere al and Surgical Reports," Boston City Hospital, ls'.i;. p. 126.) The distinction be- tween the intestinal and pulmonary forms of anthrax is not easily made, and doubtless the two may often be confounded with other acute diseases affei these organs, unless the anthrax bacillus is identified by microscopical examination, or the disease is reproduced by inoculation in animals. The diag- nosis of intestinal anthrax may be quite impossible, owing to the rapidity of its progress and the sim- ilarity of its symptoms to those of other gastro- - 1 inal diseases, especially to those of so-called "ptomaine poisoning". The course of intestinal anthrax is almost uniformly fatal, and Bell states that no case demonstrated during life to be intestinal anthrax has recovered. The actual seat of the primary lesion in anthrax of the abdominal organs is at times uncertain, but in general the disease is supposed to be conveyed by means of food, which has been contaminated by the anthrax bacillus or its spores. Keen in his - rgery" has called attention to the localization of the abdominal focus of the disease, and makes the following observation: Primary Gastric Anthrax. — "Though infection of the stomach by anthrax might reasonably be expected to occur occasionally, so far as I can discover, the condition is an extremely rare one, a case reported in the Medical Press, 1904, p. 199, being the only one 1 ran find recorded." An original article by Schmidt confirms the diagnosis of bacilli from a necrotic anthrax ulcer in the stomach. Treatment of this variety of the disease should comprise rapidly acting evacuants, followed by the administration of internal antiseptics (germicides), with supporting measures according to the conditions present; but the nature of the lesion and the rapid progress of the disease would preclude the hope of much benefit from any available means of internal medication. Pulmonary Anthrax, Wool-sorter's Disease, Anthra- cemia. — Primary lesions of the lung occur, but they are rare, and the channel through which the exciting bac- teria gain entrance to the pulmonary tissue remains in question. It is asserted that the bite of certain cts, particularly the fly and the mosquito nay convey the disease. As an aid in diagnosis, the nature of the occupation of the patient is highly suggestive. This form of the malady may be acquired by inhalation of the dust from any of the products of diseased animal-. I'll us it ha bi en ob i red among those employed in the handling or manufacture of animal hairs and woolen rags; among wool-sorters, rag-pickers, and those concerned in the further manipulations of these articles into woven textures: and to some ' among paper-makers. Dr. Bell says: "Thesoi of wools and hair- is unhealthy in proportion to the contamination they produce in the air inspired by the workmen. First, the dus( and fine short hair-, acting mechanically, excite chronic di ' the lungs, such as bronchitis and phthisis. Se< ilu-t from dried and decomposing animal ma produces a low form of septic pneumonia. Third, the virus arising from the blood and discharges of animals that have died from anthrax an- specifically on the lungs." Pulmonary anthrax is peculiarly a human complica- tion. It is not often observed as a coincident con- dition in either cutaneous or intestinal infection. '"From the paramount dignity in the human econ- omy of the organ invaded, and the specific tendi in anthrax to the development of edematous condi- tions in the tissues invaded, il is not surprising that pulmonary invasion leads to a most acvite and ge ally fatal manifestation of anthrax, rei Hi- ring but seldom." (Billings, "Twentieth Century Practice of Medicine.") Laryngeal Anthrax. — In the Munchener medizinische Tier/,, nschrift, vol. i., p. 40 >, 190d, Emil (das reports a case of this rare condition, occurring in a carpen- ter, forty-one years of age, who was brought to the Klinik on May 9. The disease began on May 2, with a feeling of chilliness, weakness, and a swelling in the region of the angle of the lower jaw on the right side. Three days before admission he suffered from nausea with acute pain in the region of the stomach. The patient rapidly became worse and the swelling of the jaw increased to a considerable degree. On admis- sion the patient was much prostrated and presented the appearance of a severe general septic infection, which seemed to have originated in the phlegmonous inflammation in the neck. The pulse was 140, very weak, almost imperceptible at wrist. The abdomen was moderately distended, sensitive only at epigas- trium. There was edema over the sternum as well as over the lower portions of the thorax and in the region of the lumbar spine. No other changes were observed on the cutaneous surface nor in the region of the swelling on the jaw, nor was there induration of the lymphatics. Xo pain in muscles or joints. There was much swelling of the right wall of the pharynx with edema of the adjacent parts, but no ecchymosis of the mucous surfaces; there was edema of the right vallecula, where the mucous membrane hung over the right side of the epiglottis in loose folds and presented .numerous punctate hemorrhages on its surface. The patient died the same night. At autopsy, the stomach showed numerous confluent edematous elevations on the posterior wall, which at many points were ulcerated and presented a black- ish surface. These swellings were scattered over the interior between the cardia and the pylorus. The aditus laryngis and the adjacent portions of the pharynx were edematous, the mucous membrane was covered with gray spots of superficial necrosis of the epithelium. Those changes extended on each side to the interior of the larynx as far as the location of the vocal cords. In the hemorrhagic edema of these portions of the submucous tissues the bacilli of anthrax were found in great abundance. The re- porter of this case said that in the Handbook of 461 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Larnygology by Heymann no mention was made of such a case, and he could find no observation of this form of primary anthrax invasion in the literature of the subject; so that this seemed to be the first case of anthrax of the larynx which has been recorded. In a communication to the Journal of the American Medical Association, Feb. 3, 1912, is another account of this rare location of primary anthrax. The patient was a young woman who had been employed in manip- ulating different varieties of wool mostly of the gray and brown Persian kind, which, however, had gone through several processes before it had reached the combing-room in which she worked. Exactly how the infection occurred is not known, for her sister, who had had anthrax, stated that nothing objectionable had been noticed in the wool which they had been handling. At the necropsy made by Mr. F. W. Eurich, bacteriologist to the Anthrax Investigation Board, anthrax was found in the larynx, from which general infection of the system had taken place. In his ex- perience a lesion in the larynx is unique and does not appear to have been previously observed. The lungs were not affected. The general duration of the pulmonary invasion before the fatal termination is from two to five days. The bacilli are often present in the sputum. Pathology. — The pathology of malignant pustule consists of the series of changes which follow inocula- tion with anthrax through either the skin, the alimen- tary canal, or the lungs. These changes are some- what different, according to the particular circum- stances of the individual case. When the virus is introduced through a scratch or abrasion of" the skin, the period of incubation, or the space of time before the local symptoms of anthrax appear, may vary from a few hours to three days; in rare cases a somewhat longer time may elapse. "No matter from what point infection occurs, when the bacillus enters the circulation widely dis- tributed changes occur in the tissues. The muscles, including the heart, are darker than normal, and frequently contain minute hemorrhages; ecchymoses may also be found beneath the serous membranes; even the meninges and brain are affected. In man splenic enlargement is less constant than in lower animals. The organ is usually increased in size, dark in color, and the pulp diffluent. The bacilli may readily be cultivated from all the organs and are often present in enormous numbers." (Coplin, Manual of Pathology.') Anthrax produces upon the external surface a somewhat elevated papule, five millimeters to several centimeters in diameter, with a central depressed seal). The corium and papillary body become infiltrated with serocellular exudate and with bacilli. The perivascular and connective tissue spaces become filled with leucocytes, and the pressure of this serous and cellular infiltrate together with the toxins of the bacteria cause the central coagulation-necroses; though suppuration does not occur unless there is a mixed infection. When the serocellular exudation extends upward to the epithelium, • it elevates the latter, and produces the typical vesication. In the edematous variety; the swelling is due to the diffuse serous infiltrate and to the effect of the bacteria block- ing or inducing coagulation in the capillary vessels. The course of the disease may be divided into three stages. The first or prodromal stage is that of incubation (period of latency). During this period the patient presents no marked symptoms of any serious disturbance. There are localized burning and itching at the seat of infection, which are gener- ally thought to be due to the bite of an insect, such as a flea, which the spot closely resembles. After a period of incubation lasting from a few hours to three days (rarely longer) the local symptoms suddenly change. The second stage, that of eruption, now ensues, in 462 which a small papule is seen at the seat of the pre- vious irritation. This rapidly increases in height and in circumference, and generally presents a spot of dark discoloration at its summit. The itching and burning increase, and within a few hours a vesicle appears at the seat of discoloration In the papule. The vesicle now rests upon an indurated base, and contains a small amount of a serous, frequently bloody fluid. In the earliest stage the bacilli of anthrax are present in the central point, but as these tissues become necrotic, the bacilli approach the confines of the lesion, where they are present in great numbers and from here they invade the tissues in the vicinity, find their way into the lymphatics and lymph glands; eventually they gain entrance to the circulation and are distributed by the blood over the system. Bacterial embolism is common. The sur- rounding skin swells so as to form a slight elevation around the vesicle, which now exhibits the peculiar appearances to which it owes its name of "malignant pustule," although this is not an accurate definition of the pathological condition at the seat of the local disease. The vesicle, soon ruptures spontaneously, or is ruptured by the scratching of the patient, and reveals a dark red base, which quickly dries, forming a livid or brownish crust. This is the commencement of the central gangrene or necrosis of tissue commonly observed in the carbuncle of anthrax. The crust becomes gradually larger, until it sometimes reaches a diameter of from one to three centimeters, ami the swelling and tension of the surrounding skin be- come more extensive. A line of new-formed vesicles develops around the margin of the crust, and the^e vesicles contain a yellowish or brown fluid content. The crust now gradually becomes free from pain and tenderness, and a doughy or boggy infiltration is felt for some distance in the tissues around the primary sore. The local condition, however, has no diagnostic value as an indication of the infection of the general system. In rare instances the local symptoms be- come less serious, the swelling subsides, the slough separates and is thrown off, and the ulcer heals by granulation. In such cases the chief danger is from septicemia arising from the absorption of gangrenous matter. It is probable that in such conditions there is a mixed infection from the presence of other bac- terial organisms. When general infection occurs the swelling increases and becomes doughy, the lymph channels are detected as reddened lines of induration, the glands become swollen, and burning heat is felt in the part, which gradually becomes very painful and later is the seat of stiffness and numbness. The veins are often seen as dark-colored channels, and are sometimes plugged by thrombosis. The foregoing appearances are caused by the local multiplication of the bacilli of anthrax in the part which is the seat of the primary infection. The germs may be found in the central part of the car- buncle and in scattered groups in the rete Malpighii. At times large interwoven masses of them are found in the tissues at this early period, and may be ob- served to spread into the neighboring parts by ex- tension beneath the epidermis. In a carbuncle extirpated by Bardeleben on the twelfth day, which measured five centimeters in diameter, the bacilli were present in such enormous numbers that the tis- sues were eve^where crowded with them; they even filled the spaces between neighboring cells and ob- scured the normal structures of the part. In a car- buncle examined by Wagner the bacilli were so abundant as to hide the normal tissues. The center of the pustule is generally the seat of hemorrhage, and the effused blood is prone to undergo putrefactive changes. This accident is also frequently observed in the edematous tissue immediately surrounding the pustule. From this center of the disease gen- eral infection of the body (third stage) may now quickly take place, sometimes requiring but a few — REFERENCE IIAXIHWniK of THE MEDICAL Si'llAU - Anthrax hours (so-called cas fovdroyants), while others occupy from three to four, sometimes eight to ten days for general poNoning of the system. \ second form of the disease is the "ccdema carbun- o uiaseu malignum,""Milzbrandoedem." Thisis observed in rases in which inoculation occurs: in pails ered with thin delicate skin, such as the eyelids, axilla, and occasionally the extremities. In the e . the local sore, the pustule, is not formed, there is no crust, no central gangrene, nor an erupt i f icles, but a rosy, bluish, or even livid swelling appears at the scat of primary infection, and rapidly spreads in all directions. Generally the spot « here t he Illation occurred may be seen as a dark point more or less elevated above the surface, but sometimes there is no visible point of origin. The swelling is [uently enormous, so that the arm may be three or four times its normal size, or the eyes may be en- tirely closed by large effusions of translucent fluid in the tissues. Like the previously described local manifestations of anthrax, this malignant edema may subside spontaneously without causing destruction of issues, and the part may be restored to its normal condition. There is generally abundant desquama- of epidermis after the disappearance of the na. At times the swelling is so enormous that the skin becomes gangrenous to a greater or less it, and often the edematous area is the seat of vesicles or blebs which are filled with a bloody serum, and at the base of which is generally found a slough comprising the entire thickness of the skin. When the neck is the scat of extensive edema and sloughing, the loss of tissue may be so great as to lay bare the i vessels or other important structures, and death may ensue from hemorrhage or from some other it not belonging to the course of anthrax. < leneral infection of the system corresponds to that period in the development and multiplication of the illi in which they have penetrated beyond the seat of primary infection, have reached the internal organs by means of the blood channels or other paths, and ■ commenced to multiply in these structures. The bacilli are probably carried by the blood corpus- el,-,, which often contain them in considerable num- bers. The disease progresses much more rapidly in the intestinal form, probably from the sudden libera- tion of larger numbers of bacilli, which enter the circulation from many points at once. The local tissue changes which ensue upon inoculation with bacillus anthracis whether the seat of infection be in the skin, the lung or the intestine, are due to a block- ing up of the capillaries of the part by the multiply- ing bacilli. The blood-stream is further impeded by the inflammatory swelling of the tissues sur- rounding the vessels, due to the irritation of the ba- cilli or their toxins, causing ischemia and necrosis. When the bacilli enter the blood stream directly or through the lymphatic system, and the infection becomes general, the bacilli are found most abun- dantly in the spleen; and the inflammation and swelling of that organ are characteristic of systemic anthrax. They are found, too, occluding the capil- laries of the liver, kidneys, and brain, causing tume- faction and hemorrhagic infarction of internal organs, and multiple hemorrhages into the skin and mucous membranes. The anatomical appearances in anthrax are those de- pendent upon a multiplication of the bacillary organ- isms in the body, and there is hardly a structure or a tissue in the dead body in which they may not be found in great abundance. They form thrombi in the capillaries, the lymphatic channels and glands; th ■ brain, kidneys, and intestinal glands are found more or less crowded with them. The most striking changes are hemorrhages in the tissues, varying in amount from mere points to large extravasations. Edematous exudations and serous effusions in the various cavities, and serous infiltration in internal ■ ■mans frequently ensue. The abdominal organ generally found in a normal condition, with the ex- ception of the spleen, which is usually enlarged and softened iii structure, and contain- enormous col- lections of bacilli. There is a marked increase in the number of white corpuscles, and death is quickly followed by strongly developed rigor morti . In general appearances the clinical picture of fatal anthrax closely resembles that of other Form virulent blood-poisoning. As a rule, cases of malig- nant pustule terminate fatally in from three to seven days, though in cases of special virulency death may occur within a few hours. The General symptoms of anthrax are usually the following: Chilliness, or a well-marked rigor, faint- ness, pains in the limbs, loss of appetite, sometimes seven' distress in the region of the stomach, colic, meteorism, vomiting, and diarrhea, frequently accom- panied by bloody stools. There is excessive thirst. The patient retains consciousness to the end, unless coma should supervene shortly before death. Fre- quently there is great agony with distressing anxiety; the patient begs for relief in the most piteous manner, and feels that dissolution must soon ensue. In other cases there is stupor from the first, or the patient becomes delirious, or sinks into a deep coma, or the body may be convulsed by clonic cramps or contin- uous trismus or tetanic contractions. Occasionally there are harassing cough and dyspnea with bloody expectoration. There may be frequent hemor- rhages in the tissues or from the mucous membranes, and sometimes secondary pustules are formed which are similar in all general characters to the primary lesion. Usually there is considerable elevation of the body temperature at the period of invasion of anthrax, the thermometer often registering 40° C. (104° F.), or higher, for some days, when there is a sudden fall to a temperature at or below normal, frequently as low as 36° C. (97° F.). The pulse is generally acceler- ated, and increases in frequency until death. The action of the heart is often feeble, and the sounds are hardly audible. Death usually occurs from collapse and general cyanosis. Cases of intestinal anthrax are generally more virulent than the ordinary forms of malignant pus- tule, and they result fatally sooner than those in which the infection takes place from the external surface. These effects seem to depend upon the me- chanical action of enormous masses of germs within the body, and upon the destruction of large portions of tissue by the growth and multiplication of the bacilli, together with the added action of the specific toxin produced by these organisms, which may be sup- posed to be more rapidly disseminated from this origin than when the initial lesion is situated upon the cu- taneous surface. See a very interesting account of "Charbon" by Larrey in his "Memoirs," vol. i., p. 59, an abstract of which, by Sir H. G. Howse, appears in the Lancet, December 23, 1S99, p. 1720. The progress of anthrax when acquired by inhala- tion is variable, but usually the course of the disease is rapid, and tends toward a fatal termination. The symptoms are often unimportant or insignificant until near the end. In some cases the invasion of anthrax is followed by sudden collapse with speedy death of the patient, as from shock; but generally there is more or less reaction, followed by collapse and death, without the signs of any inflammatory lesion in the lungs. When the patient survives a sufficient time for inflammatory processes to develop in the lungs, the risk from the anthrax poison is reduced. The duration of pulmonary anthrax varies from one to ten days. A large proportion succumb to the disease within the first four days. The bacilli may or may not be found in the blood, but if the disease is really anthrax, the subcutaneous injec- tion of the blood in a mouse will certainly prove fatal. 463 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The specific action of the bacillus upon the body of its host, aside from its presence in enormous numbers, has been sought in the morphological char- acter of the organism; the germ belongs to the aero- bic class of organisms, and is a greedy consumer of oxygen; and it has been thought, that the great pros- tration of the system, and the signs of the destructive action of the disease, as well as its rapid progress, may be due to the fact that it depletes the red blood cells of their supply of oxygen, and thus induces a sudden collapse of the vital powers. This view is supported by the appearances presented by the dis- ease in grave cases, in which there is cyanosis to a marked degree, and the patient dies with all the appearances of asphyxia. In this respect the organ- ism of anthrax produces in the animal system an effect similar to that of certain poisons of the cyanide group, in which death is uniformly associated with asphyxia. In cases in which the disease progresses slowly, the secondary toxins formed by the bacilli are probably the cause of the fever and other constitutional disturb- ances. "There can be but little doubt that in the living body the bacillus elaborates bodies which either directly or indirectly are toxic to the tissues. In no other way can the extensive inflammation and edema be explained. It is perfectly possible that in the body substances are formed which are not elaborated in cultures." Osier, "Modern Medicine," iii. 46.) The dissemination of the bacilli through the sys- tem is chiefly by way of the lymphatic channels and the glands. Only after passing these physio- logical barriers can they obtain entrance into the general circulation and pass to all parts of the body. Therefore they would not be detected by microscop- ical examination of the blood, as an aid to diagnosis, until a period when the condition of the patient is beyond relief. Very instructive results relative to the patholog- ical activity and the paths of dissemination of the anthrax bacilli in infected animals have been observed after injection into the anterior chamber of the eye of the guinea-pig. After aseptic introduction of a pure culture of anthrax bacilli in this location, the death of the ani- mal is often delayed until the fourth or the fifth day or even longer. No trace of macroscopic suppuration can be observed in the eye ; and aside from a more or less evident chemosis of the conjunctiva bulbi, one would from external appearance consider the eye perfectly normal. Examination of the aqueous humor shows that it is swarming with anthrax bacilli. By microscopical sections the path of the bacilli may be distinctly traced from the anterior chamber through the space of Fontana, following the lymph channels of the sclera and conjunctiva, as has been demonstrated by Weigert. After similar injection into the vitreous humor, according to Clifford's statement, the bacilli are transported by means of the lymph stream which leads from the vitreous through the central canal and the central vessels to the posterior part of the orbit, and from here to the cavity of the skull, from whence they are carried along the sheath of the optic nerves to both sub- arachnoidal spaces. From this location they are borne by recognized lymph channels to the thoracic duct, and thus enter the blood stream. After entrance into the general circulation, the organisms of the disease invade every tissue and organ in enormous numbers. Bacterial embolism is common; the heart muscle is invariably swollen and anemic, and at times the seat of petechial hemor- rhages. The same appearance with more or less ecchymosis may be observed beneath the endocar- dium, pleura, and pericardium, as well as in the sub- stance of the lungs. The same condition may also exist in respect to the vessels and serous membranes around and within the brain. Diagnosis. — The diagnosis of anthrax is often very far from easy. Dr. Bell says: "The slightest illness occurring in those exposed to infection from anthrax should be looked upon with suspicion until tin' possibility of its being anthrax has been nega- tived. Often it is impossible to make an early diag- nosis, as the symptoms may resemble those of ordi- nary illness. The progress of the disease is frequently not characterized by alarming indications until mar the end of life, hence not infrequently it is unre riized until the patient is cold, livid, almost pulsi and dying." The bacillus anthracis will be found in blood ob- tained from the initial lesion, both by culture methods, and from stained smears, and by inoculation of animals. The urine becomes scanty, darker, and of high specific gravity. In 1908, Royer and Holmes reported the following data: Anthrax bacilli were frequently discovered in the circulating blood both in smears, and by cultural methods. In thirteen cases, study was made in reference to the leucocytes, and in these, leucocytosis was the rule, the highest count obtained being 25,000 in a cubic centimeter, whereas the average count for all the cases was 13 In two fatal cases the leucocytes numbered 12,000 and 9,600 respectively. In eleven eases differential count gave the following averages: Polymorpho- nuclears 77.6 per cent., large lymphocytes. 17.7 per cent., small lymphocytes 5.3 per cent., eosinophils :; c per cent., basophiles 0.1 per cent., myelocyte- 0.4 per cent. The occupation of the patient may afford a valuable clew, or at least awaken suspicion of the disease in a given case. Under such circumstances, a papule upon any exposed surface of the body would exi apprehension of the disease, thoi gha positive diagi might at this time be impossible. When the di has advanced to the vesicular stage with serous exuda- tion, there would be less uncertainty as to its nature. Implication of the lymphatic channels and swelling and tenderness of the neighboring glands would add weight to the probable diagnosis, though all these symptoms may be associated with other infections diseases. The most certain method is that of taking a drop from the contents of the pustule or vesicle, and subjecting it to microscopic examination. If the case is one of anthrax, this fluid will be seen to con- tain the bacillus. This at once establishes the character of the disease in distinction from simple non-specific carbuncle and furuncle. In doubtful cases the liquid may be subjected to cultivation in a moist chamber, when a definite result may be obtained within a few hours. Or the experimental inoculation of guinea-pigs and rabbits or other animals susi tible to the disease may be carried out; and if anthrax develops in them, there will then be no doubt in regard to the nature of the malady ; but a negative result does not entirely exclude malignant pustule. In districts in which malignant pustule is known to prevail, the surgeon would suspect this disease in the early stages of simple carbuncle, or of furuncle, and in the stings of wasps and other insects. Malignant pustule also resembles to some extent the early stages of erysipelas. Boils or furuncles are frequently very similar in their early stages to the first appear- ances of anthrax. In certain tissues they often commence by the development of a vesicl the seat of irritation. In furuncle, however, there is not so extensive inflammation in the vicinity, and the central gangrene, the crust, the wreath of vi - ieles, and the febrile action are absent ; these symptoms belong exclusively to anthrax. The ordinary simple carbuncle is very painful, the carbuncle of anthrax, on the contrary, is only slightly sensitive. Bites of insects generally show a small yellowish point, which is not observed in anthrax. Erysipelas, especially when accompanied by serous effusions (bulla:), re- sembles the malignant edema of anthrax to some 464 REFERENCE HANDBOOK OF Till'. MEDICAL SCIENCES Anthrax extent, but in erysipelas the chill and lever usuallj precede the eruption of the disease, while in anthrax these occur simultaneously. Anthrax distinguishes itself from erysipelas in the following ways: Erysipelas begins most often with a chill; in anthrax edema the fever appears afterthe edema is present. Erysipelas has always the vivid , ,1 border, which is slightly above the level of the normal skin in the vicinity; its accompanying edema is much less pronounced than is that of anthrax, and is limited to the immediate vicinity. In anthrax the redness gradually shades to normal color and the edema extends beyond it into the tissues of the parts. The Ascoli reaction by precipitin makes possible the diagnosis of anthrax even in cases in which the microscopical and cultural evidence and that from inoculation of animals have proved negative. There- in is specific, as the characteristic "ring-forma- is never obtained with material or organs from ces not containing the anthrax infection. The establishment of the diagnosis succeeds also with organs infected with anthrax even when they have been preserved in alcohol for four months, whether or not these organs have previously given a positive ! act etiological diagnosis. The "ring-formation," a peculiar cloudiness, appears most promptly and distinctly by employment of extractive sub- es from the spleen. This method makes it possible to prove the precipitinogen of anthrax not only in fresh filtrates of visceral organs, but also in material which has been preserved on ice for more than three months. The extractive may be prepared by means of physiological salt solution, or by dis- tilled water or ordinary water. The intensity' of the reaction and the promptness of its appearance are modified by the dilution of the extractive, and by the reduction of the amount of precipitin contained in the serum; while putrefaction of the extractive - not materially interfere with its accuracy. This new test and its technique are thus described by Prof. Dr. Alberto Ascoli, in Zeitschrift fur Initnii- mtatsforschung vnd experimentelle Therapie, 1911, Erstes Heft, Lifter Band, p. 103. The technique of the thermoprecipitin methods consists of the two follow- ing proceedings: (1) Boiling of the suspected mate- rial in five to ten volumes of physiological salt solu- tion, which may be rendered acid by addition of acetic acid in proportion of 1:1,000, if desired: this need occupy only a few minutes, and the resulting fluid is filtered, preferably by means of an asbestos filter. (2) Examination of the clear filtrate by means of a layer of precipitating serum, with a control-tube treated in the same way with normal M'i am, This method has been in constant use in the vet- erinary high schools of Milan, Modena, Parma, and Naples, and the author has employed it in hundreds of personal examinations, with the result that its '""elusions in every instance agree with those of microscopical examination, and also prove effective even when the material obtained for examination is already in a stage of putrefaction. This peculiarity pecially recommends the method when the sus- pected material is obtained from animals which have been found dead, or are removed from a distance to 'he place of examination. lor the ready performance of this test, the author has recommended the following simple appliances; ( I I A tall, slender reagent-glass with a suitable foot for support; (2) a small funnel, with an attachment at the lower end, which is drawn out into a long tube, bent at nearly a right angle, and ground at an angle .-o that the resulting filtrate will be discharged on the side of the receiving tube; a portion of asbestos in the bottom of the funnel makes the best kind of filter. The test is carried out as follows: The test-glass is filled to a certain definite point with water, in Vol. I.— 30 which is then dissolved a proper amount of salt, BO as to make the physiological solution. In a test-tube of ordinary character, a leu grams of the -u pected material is suspended in water, and I lie iiiti.' i- placed for a lew minutes in boiling water. When the tube litis cooled, this fluid i poured into the funnel with the asbestos filter, which is placed in the top of the glass first described: as the clear fluid Hows slowly dow n the inner surface of the reagent-glass a ring- formed cloudiness is soon observed if the material added contains anthrax infection. With material which contains no anthrax infection, the te I hi no cloudiness. This reaction therefore would appear to be a valuable and time-saving addition to our pie ent means of diagno is in tin di ease. In glanders the carbuncles are smaller, generally multiple, and accompanied by intense febrile reaction. Cases of intestinal anthrax, mycosis intestinalis, may be very difficult of diagnosis. The symptoms often resemble those of poisoning by arsenic or phosphorus, though the appearances due to anthrax are frequently more suddenly developed and advance i e rapidly to a fatal termination than in cases of poisoning by these substance . Often the patient is dead within a very few hours. Prognosis. — The prognosis in anthrax is always very grave, but is least so in the cutaneous form where the local lesion is well marked and lends itself to local therapeutic measures. When death ensues, it follows as a result of general infection. The pulmo- nary type gives the highest death rate, fifty per cent., according to Eppinger; seventy-five per cent, as estimated by British writers. The collective mortality to be expected from all forms of anthrax in man, treated and untreated, is about twenty-five per cent. In Great Britain during the six years, 1S99-1904, 267 cases were reported, with sixty-seven deaths. Pulmonary and intestinal an- thrax and those eases,- at first localized, in which general infection supervenes are almost invariably fatal. The mortality varies greatly in different countries and climates. Anthrax in the tropics is less fatal than elsewhere, probably because of the attenuation of the virus in high temperature and sunlight. Extensive eruption and multiple pustules render the prospect of recovery less favorable. In children and in feeble persons the disease is almost always fatal. Pregnant women are especially liable to abor- tion from the invasion of anthrax. The prognosis in cutaneous anthrax bears a direct relation to the promptness and thoroughness with which the local lesion is treated. If the seat of the primary invasion be destroyed by efficient cauteriza- tion or complete excision before the bacilli have entered the lymph channels or gained access to the blood-ves- sels, a fatal result need seldom be apprehended. Fagge states: "Hitherto, so far as I am aware, no instance of recovery from the intestinal form of an- thrax has been recorded. In pulmonary anthrax the spleen is less subject to enlargement and softening than in any other form of the disease. The appear- ance of any illness of however trifling nature in a per- son exposed to the infection of anthrax should lead to a very guarded prognosis until such a time as the disease may prove to be some other ailment. The greater number of cases of anthrax are fatal within four days from the appearance of the first symptoms. Pronounced febrile reaction with chill and a tempera- ture above 102.5° F. would be a possible sign of successful resistance to the entrance of the bacilli into the general circulation, and the localization of the disease to the seat of invasion. No recorded case in which the presence of the bacilli in the blood has been proved has recovered." The danger to life cannot be estimated by the extent of the local lesion. The prognosis is more favorable 465 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ■pith a high temperature than with a lower degree of fever. A falling temperature with increase of the gravity of the general symptoms, is a precursor of a fatal result. Duration of illness in intestinal anthrax: Number of cases fatal within 3 days, 3 ; -1 days, 23 ; 5 days, 11; 6 days, 13; 7 days, 12; 8 days, 6; 9 days, 6; over 9 days, 2; total S3. In pulmonary anthrax: Number of cases fatal within 1 day, 5; 2 days, 22; 3 days, 21; 4 days, 16; 5 davs, 7; 6 days, 3; 7 days, 3; 10 days, 2; over 10 days, 3; total 82. Mortality. — In Europe, about twenty-five per cent, of all cases prove fatal. Thus in Great Britain, of 320 reported cases (1899-1905) eighty-five were fatal^ 26.6 per cent. Of these, thirteen were of the internal variety, and all were fatal. Excluding these, the proportion of deaths to attacks in the cutaneous form was 23.4 per cent. In Italv, in eleven years (18S0- 1890), of 24,052 cases 5,812 were fatal — 24.1 per cent. Koch (18S6) noted 422 fatal cases out of 1,473 pub- lished cases of cutaneous anthrax — 32 per cent. In pulmonary anthrax among rag-sorters in Lower Austria (1870-1SS6), the mortality was 88.6 per cent. It is universally agreed that neglect of early treatment in cutaneous anthrax is one cause of its high death rate. At Guy's Hospital between 1S96-1904, of fifty- six cases treated, only four proved fatal — 7.1 per cent. The number of cases of anthrax contracted in factory or workshop (England) during the period from 1899 to 1905 was: males, 270; females, 50; total, 320; fatal, 85; the mortality was therefore 26.6 per cent, of these cases. (Bell and Legge give a valuable resume: ■ of the pathological conditions in cases of the various forms of anthrax, with records of autopsy findings in each form.) Industrial Anthrax. — Anthrax is still a fairly com- mon disease in Great Britain. In the Journal of Hygiene for June, 1912, E. E. Glynn and F. C. Lewis present the following table of cases' of the disease in man in Great Britain and Ireland: 1906 1907 190S 1909 1910 Total Cases 76 71 69 71 79 366 Deaths 26 15 13 15 12 81 The total number of cases among agriculturists was: in 1906, 8; 1907, 12; 190S, 19; 1909, 15; 1910, 24; total, 78. Of these 78 cases, 5 occurred in housewives, 16 in farmers, and the remainder in butchers, knackers, etc. There is no doubt that industrial anthrax is con- tracted by handling infected hides, wool, etc., but the reason for the dissemination among domestic animals is much more obscure. Many believe such animals contract the disease by feeding upon infected pastures, but recently a considerable amount of evi- dence has been collected which indicates that arti- ficial foodstuffs or manures may carry infection. With regard to the former possibility, Stockman (1911) has noted, first, that S3 per cent, of the out- breaks of anthrax, in the six worst infected counties in Great Britain during five years, 1905-1909, occurred upon new farms, that is to say farms in which there had never been a previous case; consequently it was unlikely that the animals contracted it from infected pastures; and second, that in 6S per cent, of the outbreaks the evidence pointed, after careful elimi- nation of other causes, to infection with "artificial feeding stuffs or manures." Again anthrax is least common from July to October when the stock are on grass, but there is a decided rise in the following months when they may be "assumed to be running in and receiving artificial food." B. anthracis has very rarely been found in these artificial foods, though M'l'adyean (1S95) once detected it in a linseed cake, which caused the death of six shorthorns, and ampng .some oats responsible for an outbreak in London horses; similar cases have occurred in Germany (Legge, 1905). We have recently detected anthrax bacilli in a sample of pea meal, used for feeding cattle, one of which died of anthrax; the investiga- tion will be alluded to subsequently. The importance of ascertaining the origin of agri- cultural anthrax is seen from the second table, which indicates that in spite of Government inspection the disease appears to be spreading. In the last five years the number of deaths among domestic animals have increased from 306 to 406 per 100,000, i.e. by 59.3 per cent.; the number of outbreaks have in- creased even more, i.e. 59.3 per cent.; and lastly, t he number of cases amongst agricultural laborers and others have also increased from 8 to 24 per annum. Of course some of this increase may be due to more systematic notification of the disease. Anthrax spores have been demonstrated by the inoculation method in 21.3 per cent, of 141 samples of industrial material, supposed to have produced anthrax in Liverpool amongst those who handled them. Of these samples 286 per cent, were from hides, 20.2 per cent, from wool, 20.6 per cent, from hair, and 7.1 per cent, from bones. The largest proportion of infected samples came from Singapore. Anthrax appears to be steadily increasing among domestic animals, and consequently a larger number of agriculturists are becoming infected. The rea- son for this dissemination amongst animals is still obscure. We have found B. anthracis in a sample of pea meal used for feeding cattle confined to a shippon, one of which died of anthrax. The meal was prob- ably infected from the sack. Anthrax is preventable among men and domestic animals; and its ultimate suppression depends largely upon the certainty with which bacteriologists can demonstrate the presence or absence of bacilli in suspected industrial food, or other materials. (Glynn and Lewis, Journal of Hygiene June, 1912.) Prophylaxis. — As the diseased or dead body of a human being or an animal, and the substances emanat- ing from the same, form the source of danger from anthrax, it is evidently important that these sub- stances should receive special attention. The excreta or discharges of any kind from those sick with the disease should be carefully disinfected and burned, and the bodies of animals or human beings dying from the disease should be immediately wrapped in some efficient disinfectant and cremated. No post- mortem examination should be allowed, as thereby the opportunity for further infection is largely in- creased. The physician should warn the attendants, in cases of anthrax, of the danger of infection from the discharges of the patient. No person having a wound or abrasion on an exposed part of the body should take any part in the care of the patient, or touch anything which has been in contact with or near him. All band- ages, dressings, etc., should be immediately burned. Especial attention should be given to the exclusion of flies and mosquitos, which have been proved to be the active carriers of various contagia. Unneces persons and all visitors should be rigorously excluded. The prophylaxis of anthrax must at present be regarded as unsatisfactory, until other and more stringent precautions are adopted to effect efficient sterilization of the commercial animal products deri from countries in which anthrax is either prevalent as a permanent infection, or at times appears in epidemic form. Osier states: "The ordinary processes of tanning leather do no't affect the spores of anthrax; and the writer has kept them immersed for 240 days in the strongest tanning fluids — twice the usual time required for the process — without any perceptible change in their vitality or viruleney. Spores are not formed in cultures "kept at temperatures below 18° C, nor in those above 42° C. ; when grown at a temperature above 42°, the bacillus loses the power of forming 466 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Anthrax spores, ami becomes gradually attenuated, and ac- quires' vaccinal properties. When brought to this condition, the attenuated bacillus may be cultivated at ordinary temperatures, without regaining virulence or the spore-forming power. The vaccines of Pasteur are prepared in this manner, the degrees of attenua- tion depending upon the number of days the culture is kept at 1-'° I" -13° C. The first or weakest vaccine is grown for about twenty-four days, at I lie end of which nine it has lost the power to kill larger aninals and i guinea-pigs, bin will still kill white mice; the ,1 vaccine is grown for about twelve days, and ild kill guinea-pigs, but not rabbits. In practice, an interval of twelve to fifteen days is allowed to elapse between the two inoculations, which are made itaneously." ("Modern Medicine," vol. iii., p I'''.) Warren-Gould in the last edition of the "Inter- national Text-book of Surgery" (1902), p. 191, when ussing human anthrax, add the following, which M properly be regarded as belonging to the n\ lactic considerations of this malady: "The disease is transmitted to man from infected animals; t he atrium of the microbe is usually an abrasion of the skin, but the bacteria can enter by the lungs and the intestines without the occurrence of wounds. Flies are said to transmit the disease (Koch), and the bristles from which brushes are made have conveyed microbe." "Surgeons have repeatedh' con- veyed the infection by using imperfectly sterilized catgut from sheep suffering from splenic fever." "Pathologists have frequently been infected while making postmortems of experimental animals dead of the disease." The inoculation of the vaccines and toxins of an- thrax is an efficient preventive of the disease in ani- mals. The blood serum from an immune animal, if injected subcutaneously into a susceptible animal, will afford a certain degree of protection against sub- gequent infection with anthrax. The following state- ment is from Sajou's Annual for 1S9S: "A sheep was immunized until it could bear the injection of seven agar cultures with but slight elevation of temperature. A lamb was immunized likewise to the highest degree, and blood was taken from the carotid to obtain serum. With the serum of the sheep it was actually possible save from death a rabbit in which an extremely virulent culture of anthrax was injected either after or simultaneously with the serum. Evident thera- peutic results were obtained with this serum in animals that had received the anthrax bacilli previous to the injection of serum. These results permit us to hope that anthrax in man and the domestic animals may sometime be treated by serotherapy." (Vaughan, "Twentieth Century Practice," vol. xiii.) It is further stated that "French skins, since Pasteurian inoculation has been employed among the French flocks, have been found rarely to cause anthrax." Bell makes the following statement: "No efficient system in relation to the spread of anthrax has been yet possible. To accomplish this end there should be a careful separation of the infected wools, hair, hides, rags, etc., at their source, often in distant countries. This is manifestly very difficult to accomplish." In the subsequent handling of the materials during the processes of preparation and manufacture, every effort should be made to protect the workers from the dust arising from such materials, which should be removed by air draught and burned. Sterilization of all suspected substances by steam under moderate pressure has been found useful in the treatment of other infected substances, and would doubtless pro- vide efficient protection against this disease. Page says (Journal of Hygiene, December, 1909) that "we may conclude that disinfection of horsehair by steam cannot absolutely be relied upon; but that with due care the number of anthrax spores may be diminished, and the vitality of the remainder lowered without appreciable damage to the hair." That steam is ever likely to be certainly effective in disin- fecting horsehair is improbable, since the damper the steam the better chance of destroying the spon , but the greater the damage to the hair; and the dryer t he steam I lie less chance of destroying the spore- and the less damage to the hair. These antagonistic results produce a deadlock, [n Nuremberg, one of the chief brush-making towns in Germany, regulal ions are carried out, all raw materials being disinfected by steam; yet cases of anthrax still occur, though less in number. The vapor of formalin would probably be destructive to the germs of anthrax, and possesses the special advantage thai the texture of the suspected materials is not injured by I he process. Fagge says: "The system of prophylaxis by inocu- lation of anthrax virus attenuated by transmission through suitable animals promises important results, and its study indicates a close analogy to the relation of eowpox to smallpox." Tueatment. — From the earliest times, all writers on the treatment of anthrax have recommended destruction of the primary focus by causticsor cauteries. The actual cautery is still the chief treat- ment in many parts of Russia, Siberia, Persia and other countries of Asia, where the disease is most prevalent. In England, surgical interference in cutaneous anthrax usually takes the form of free excision, and swabbing the wound with pure carbolic acid. At Guy's Hospital, in addition to this, powdered ipecacuanha is commonly dusted on the wound, and is given in ten-grain doses internally. The guide in this treatment was Muskett in South Africa, who regarded ipecacuanha as a specific for anthrax, and by this means had treated fifty cases without a fatal issue. Washbourn also found that ipecac destroyed the bacilli of anthrax, but not the spores; these latter however are not found in the animal body. The usual treatment of external anthrax in the past has therefore consisted in the application of varied medication to the local lesion, or in excision of the pustule: a glance at the mortality shows how ineffectual these measures are. When excision is performed early, it will in many cases be followed by a diminution of the edema and a fall in the tem- perature; but the mechanical injury done to the tissues by the knife, and the opening of new paths of infection through the lymph-sinuses and the blood- vessels, and the resulting scarring and disfigurement, especially about the face, must be regarded as ob- jectionable features to this plan of treatment. More recent observers have discountenanced operative interference in anthrax. In the Muenchener mi ilizinischer Wockenschrift, Dec. 26, 1911, is con- tained a review by Wolff and Weiwioski. This article presents an account of the cases of anthrax observed in that Clinic since 1900, with a short abstract of the clinical history and the course of each case; with the treatment in each patient. There were thirteen cases, of which six are classed as " severe, " and seven as of a mild form. In estimating the gravity of the several cases, the temperature was considered less valuable as an indication than the general appearance of the patient, the location of the lesion, the extent of edema, and the degree of swelling of the lymph glands. In one of the severe cases, a physician had already made an incision into the lesion, and in the Clinic the patient was also treated by the Bier method after operative treatment by another practitioner. This ease was the only fatal one in the series of thirteen; i.e. 7.7 per cent. In one other severe case the primary lesion was on the right thumb: the patient was a brush-maker, and was wounded by one of the implements used in the manufacture of brushes. Three days later, when admitted to the hospital, the 467 Anthrax REFERENCE HANDBOOK OF THE MEDICAL SCIENCES entire thumb as well as the corresponding matacarpal region was of a livid color, and presented several bulla? the size of a pea. The entire hand and the forearm were much swollen and indurated. _ Two very small incisions were made in the diseased tissues near the root of the nail (not in the healthy tissues); no pus was found; but anthrax bacilli were found in the content of the blebs. The patient was discharged on the eleventh day. with the wound nearly healed. The treatment employed in ten of these cases was absolutely conservative, and consisted with slight variations, in dressings of boric acid, tincture of iodine, etc., and light bandaging. The great, -I reliance was placed upon absolute quiet on the part of the patient, with repose of the seat of the disease. The writers add: "In view of these results, we can express ourselves in thorough approval of the con- servative treatment of anthrax." Strumpell ("Handbook of Medicine", 1912) ex- presses his opinion as follows: The treatment of malig- nant pustule is surgical. Cauterization with caustic potash, nitric acid, or carbolic acid has been found ineffective and even injurious. In mild cases moist applications of aluminum subacetate, ice-bags, and the like are sufficient. In severe cases experienced surgeons advocate the division of the pustule, applica- tion of the thermocautery to the circumference of its base, and the injection of tincture of iodine in drops into the border line between the inflamed and the healthy skin. Rigidly conservative measures of treatment have been advocated by many writers. Among these, Mnller treated thirteen cases, and Rammsted seven cases, by rest, fixation, and the local application of mercurial ointment: Strubel recommended applica- tion of very hot cataplasms, supplemented by in- jection of solution of carbolic acid: and Schultze applies hot compresses of one-per-cent. mercuric chloride solution in eighty-per-cent. alcohol. (Musser and Kelly, "Handbook of Practical Medicine", 1911.) The most important progress in recent years is the introduction of the serum treatment for both local and general anthrax infection. Previous to this, we find in the literature the discussion of the following methods of treatment: (1) Expectant, (2) antibacterial, (3) complete excision of the local infection. The expectant treatment is based on the fact that man is not highly susceptible to the anthrax bacillus, and that clinical observations have indicated that manipulation of the local infection is apt to be followed by death from general infection. Bacterial in- vestigations have demonstrated that anthrax is fatal to man only when the bacilli get into the general circulation. Injection of Carbolic Acid. — Strubell is the chief advocate of this method of treatment. It consists in the hypodermic injection of a three-per-cent. solution of carbolic acid, in amounts of ten to fifteen minims. These injections are sometimes given thirty times in a day, and as many as 400 such in- jections have been required in one case. They are made around the area of infection. Combined with this treatment, the infected area is covered with poulti- ces at a temperature as high as 63° C. He reports two cases, both of which recovered. (Musser). This treatment as described by Strubell, on the whole, seems popular. I find a successful case recorded by Voigt; recovery took place after 300 injections of carbolic acid, without symptoms of any toxic effect therefrom. Caforio and Corseri advocate similar in- jections of a one-per-cent. solution of corrosive sublimate. Caforio reports eighteen cases, in some of which the infection was very grave, associated with edema and genera] symptoms. Cipriani advo- cates injection of a one-per-cent. solution of chinosol. His experience with carbolic acid and nitrate of silver solutions indicated danger of intoxication from thee substances. Musser adds: "The good results in these various methods speak favorably for the prognosis of anthrax in man. On the whole, I should recommend the complete excision of the pustule if possible, and the disinfection of the open wound with pure carbolic acid. However in view of the results after conservative treatment, or after injection of carbolic acid, one would hesitate to per- form a mutilating operation. In such an event, I should recommend the injections of pure carbolic acid; if properly performed, it is distinctly a stronger antiseptic, and experience with carbolic acid has cli -a rly demonstrated that there is less danger of poisoning when the pure acid is used, than when solutions are employed. The very hot poultices recommended by Strubell should be used, whether excision is practised or not." Scharnowski treated fifty consecutive cases by subcutaneous injection of carbolic acid with only one death. In a remarkable case reported by Strubell (Muenchener med. Wochenschrift, xlviii., p. 152G), the nose was the seat of inoculation and of the primary lesion: excision was impossible, and the face and neck were extensively inflamed and edematous. The patient received in eighteen days more than 400 hypodermic syringefuls of three-per-cent. solution of carbolic acid in the vicinity of the affected parts, and recovered without having at any time showed toxic symptoms from the drug. In anthrax, there would appear to be a special tolerance for carbolic acid. When the primary lesion is recognizable, and its size and location permit, most surgeons practise exi ision, followed by the actual cautery, or by ninety- five-per-cent. carbolic acid. This is the usual practice in England, even when Sclavo's serum has been employed. Where excision is not possible, free multiple incision with cauterization has been recom- mended. Objection has been raised by Mueller to incision, on the ground that it may open the way for the bacilli, up to that time successfully isolated by nature, to enter the blood stream. Under this idea, Mueller and Ramsted have reported twenty consecu- tive cases of localized external anthrax treated ex- pectantly by no other measures than rest, fixation and elevation of the part, with local cleanliness or antisepsis (in some cases with mercurial ointment), good diet and stimulation. All recovered, though several were severe cases, and in one the tongue was involved in the disease. (See Milroy Lectures, "Industrial Anthrax," T. M. Legge, Brit. Med. Journal, 1905.) If any operation is done in a case of anthrax, it should not be done in the ordinary operating-room of a hospital, but in a separate room. After the opera- tion, the floor and walls should be thoroughly disin- fected, and a bacteriological examination of the floor should be made, in order to determine if disinfection is effective. In Keen's case at the Jefferson .Medical College Hospital, three disinfections were required, with formaldehyde, pure carbolic acid, and strong bichloride of mercury before the floor was germ-free. In the closing sentences of the section on the treat- ment of anthrax in the previous edition of this Hand- book may be found the following: "From the results obtained in the study of other specific organisms affecting the human body, or that of animals, it, would seem reasonable to hope and expect that further research may furnish an efficient remedy in the form of an antitoxin (or vaccine) in anthrax, such as has been obtained in respect to some of the other of the bacterial infections, particularly human diphtheria." This prospective ami desired result has been already realized, in keeping with the progress of serum therapy in other diseases. An immunizing agent has been developed which promises to be .as effectual in the treatment of anthrax, as the antitoxin has been in the treatment of diphtheria. Toussaint in 1880, Pasteur in 1SS1, Marchoux in ISO"), Sobern- heim in 1898 and again in 1902 and 1904, have con- liis REFERENCE HANDBOOK OF TIIK MEDICAL SCIENI ES Anthrax tributed important papers upon the subject of im- munity to anthrax, based on their experimental work. Bclavo in June, L897, began treatment of anthrax in man by means of a serum prepared from animals after combined active and passive immunization treatment (simultaneous inoculations of serum and virus), from which the most powerful serum is ob- tained. In 1903 he collected a series of 104 cases with two deaths, a mortality of three per cent. The serum has no deleterious effects, and in the hands of its originator and others, especially in Italy England, the results substantiate the claims thai have been made for it. It assists in the destruction of the bacilli before they become so numerous that their distribution increases the danger of fatal poisoning by the toxins set free through the disintegration of the bacilli. "Judging from the experience of those who are best qualified to speak, the treatment of anthrax should consist in the administration of o's serum, in the excision of the pustule, and in the application of certain bactericidal agents.'' Prof. Sclavo of Siena, after much experimentation has produced a bacterial protective serum from the a--, which he asserts to be harmless, and 'which he subcutaneously in doses of 20 to 40 e.c. or, in cases, of additional amounts of 10 c.c, intra- venously, to be repeated if necessary. He does not practise excision or cauterization of the local lesion. He states that improvement almost immediately follows the injection of the serum, and reports 16*0 3, with a mortality of six per cent. In two of these cases that recovered, the bacilli had been demonstrated in the urine, and in one of these, in the blood as well. Recovery in a case of anthrax in which the bacilli were found in the blood has never been reported from any other form of treatment. Within twenty-four hours after the treatment the bacilli disappeared from the fluid of the vesicle. In July, 1S97, Sclavo began to treat cutaneous anthrax in man by the curative serum obtained by his method from proper animals. Sclavo directs as the initial treatment, that 30 or preferably 40 c.c. should be injected in four doses of 10 c.e. each, in four different places in the abdominal wall. On the following day, if there be no improvement either in the local or general symptoms, 30 or 40 c.c. should be again injected in the same manner: and where the symptoms are very grave, 10 c.c. additional may be injected intravenously into one of the veins on the back of the hand, and repeated if necessary. A rise in temperature following the injection is regarded as a favorable sign. If kept cool and in a dark place, the serum remains fully active for at least two years. Sclavo would rely solely on the use of his serum. In England, the inclination has decidedly been to employ it in all cases in the doses recommended by him, but, in addition, to excise the local lesion, or inject carbolic acid in five-per-cent. solution into the tissues around the local focus. Sclavo refers to a considerable number of cases of cutaneous anthrax in Italy, treated by his serum with a mortality of 6.09 per cent. as compared with a mortality of 24.1 per cent, for all cases in Italy. Dr. T. M. Legge has published details of sixty- seven cases, in fifty-six of which serum alone was used: excluding one fatal case, and two, in which there was loss of tissue, the duration of the illness from commencement of the treatment until recovery, appears to have been not more than fourteen days in any of the fifty-three cases; and in forty-four of them, the average duration was eight days. Among these cases were none of the intestinal or the pulmonary variety. Mendez of Buenos Ayres (1904) refers to 1,073 cases treated with serum from the horse, im- munized by him in the same way as was done at first by Marchoux and Sclavo, with a total of forty-four deaths — 1.19 per cent. "Sclavo's (1903) claim as to the effects of antianthrax serum may be summarized as follows: (1) Antianthrax serum even in very large doses is inocuous and can be well borne even when introduced into the veins. (2) No case taken in an early stage or of moderate Severity is fatal if treated with serum. (3) With serum a ■ cases arc saved when the condition is most critical, and the prognosis almost hopeless. I I ) When injected into the veins the serum quickly arrest s the extension of the edematous process so a to reduce notably the dancer of suffocal ion which exists in many cases where the pustule is situated on the face or neck. (5) The serum, if used soon enough, reduces to a minimum the destruction of the tissues where the pustule is situated, and tints avoids deformity (6) In some situations of the pustule, as the ej e-lid, serum must be used in preference to any other treat- ment, it being the only our which holds out hope of success without permanent injury, and in cases of internal anthrax the early injection of serum intra- venously is the only remedy likely to be successful." (From contribution to "Industrial Anthrax" in Journal <ymp- tom as in acute poisoning. The stools are at first normal: later, there may be diarrhea, usually alternat- ing with constipation. The time at which death occurs depends chiefly upon the size of the doses and the frequency of their administration. Taylor col- lected five cases, four of which were fatal. In throe, death took place in six, eight, and nine days respect- ively; in the fourth, the poison was administered over a period of three months preceding death. In the treatment of chronic poisoning it is essential to prevent the further administration of the poison. Stimulants, tonics, and nutritious diet are required. In chronic cases elimination can be assisted by ad- ministration of the iodides. Trichloride of Antimony. — Butter of antimony is a transparent, fusible, crystalline substance, which, on exposure to moist air, rapidly deliquesces to a clear liquid. When pure it is colorless, but it frequently contains more or less chloride of iron, which imparts to it a color varying from yellow to dark brown. It is decomposed by water, with the formation of hydrochloric acid and an insoluble white basic chlo- ride, which may be distinguished from the corre- sponding basic chloride of bismuth by its solubility in tartaric acid. A concentrated hydrochloric acid solution of the chloride has some uses, and has given rise to a few cases of accidental or suicidal poisoning. It is a violent corrosive and irritant. The symptoms resemble closely the symptoms produced by the mineral acids. They come on very rapidly, and consist of violent vomiting and severe pain in the throat, stomach, and abdomen, soon fol- lowed by symptoms of collapse. Death has taken place in two hours, and has been delayed for ten and one-half, eighteen, and twenty-four hours. The smallest quantity required to destroy life is unknown. Ninety cubic centimeters (three fluid- ounces), approximately, of the solution has proved fatal to adults in three cases. Recovery has taken place after 30 c.c. (oj). The lips, mouth, and throat have usually been found more or less corroded. The interior of the stomach and upper part of the small intestines are intensely inflamed, corroded, and sometimes black, as if charred. In a case related by Taylor, the whole alimentary canal, from the mouth to the middle of the small intestines, presented this black appearance. The mucous membrane was entirely destroyed, and the parts beneath were so soft that they were easily- torn with the fingers. Fatty degeneration of the liver, kidneys, heart, muscular tissue of the diaphragm, and cells of the gastric glands was observed in rabbits to which small doses of trichloride of antimony were administered ( Salkowsky) . Treatment consists in the administration of sodium Vol. I.— 31 481 Antimony REFERENCE HANDBOOK OF THE MEDICAL SCIENCES carbonate, chalk, or magnesia, to neutralize the free acid, and of preparations containing tannic acid. Edward Curtis. R. J. E. Scott. Antiperiodics — The various malarial fevers are all characterized by a more or less regular recurrence of their characteristic symptoms, to wit: chill, fever, and sweating; the period for such recurrence varying according the the life cycle of the particular organism which causes the special type of fever. These phe- nomena are therefore spoken of as periodical, and the remedies which are known to exert an inhibitive effect upon them are called antiperiodics. This term, how- ever, is a relic of the time when the nature of malarial diseases was not understood and their distinguishing symptom, periodicity, attracted an undue attention. It is not as mere interrupters of a periodic morbid phenomenon that the remedies hereunder mentioned are to be regarded, but as inhibitory of the growth in the red corpuscles of that organism whose successive crops produce the periodic symptoms of chill and fever. The actual antagonisn of quinine in the circulating blood to the development of the malarial plasmodium has been abundantly demonstrated, and with the .laying of stress upon this fact the weakness of the term antiperiodic becomes apparent. It is retained here out of deference to long established usage rather than for its present appropriateness. The symptoms against which antiperiodics are most commonly employed are those constituting the seizure in the estivo-autumnal, tertian, and quartan types of ague, and consisting of the cold, the hot, and the sweating stages. In the milder forms of intermittent and remittent fever, the breaking up of the recurrent chills as soon as possible is important for the comfort of the patient, but in the so-called "pernicious" malarial fevers, it may be a matter of life or death to stop at once those congestive chills whose effects are so alarming, and it is in such cases that the great value of the antiperiodics is seen. Other chronic manifesta- tions of the malarial cachexia, such as neuralgia, are amenable to antiperiodic treatment, but it is notice- able that the success of quinine in the relief of neural- gia is in proportion to the regular periodicity of the attacks, i.e. to the activity of the malarial organism, rather than to its sequelse. By far the most important antiperiodic — of more value, in fact, than all the others taken together — is cinchona, with its derivatives. Ever since the cure of the Countess of Cinchon of an ague at Lima, in the earlier half of the seventeenth century, first gave name and fame to the drug, its value in intermittent fever has been acknowledged. More than any other remedy in the Pharmacopoeia it deserves to be con- sidered a specific. Its direct action on the malarial parasite in the blood has been abundantly shown. Quinine, by reason of its more concentrated and convenient form, is now used almost entirely to the exclusion of cinchona as an antiperiodic. For this purpose the dose must be large, corresponding in quantity to the so-called antipyretic dose of the drug. The quinine should be so administered as to produce a saturation of the patient's system at the time w lien the next seizure would occur. To attain this object we may best give one full dose, one to two grams (gr. xv. to xxx.) on the drop of temperature following a given paroxysm in order to abort the following paroxysm. Or it may be given in divided doses through the twenty-four hours before an expected chill, the last dose being six hours before the time the chill is due. If the interval is much shorter than this, the chance of aborting the very next seizure is diminished. If a single administration of the drug anticipates the chill by only four or five hours, the chances are about equal for and against its success. In no other form is quinine more effective than in that of the crystals of the sulphate in an acid solution (bisulphate) or dissolved in lemon juice. The solubility is usually somewhat impaired in the pill form, and the administration in coffee fails to give the best effect because of the imperfect solubility of the tannate. The manufacturing chemists have put upon the market a "compound syrup of licorice," which quite effectually disguises the bitter taste of the drug, without, so far as the writer knows, interfering with its solubility. When the periodicity of the intermittent fever is irregular, and in cases of remittent fever, cinchonism should be produced as soon as possible after a seizure, and maintained by moderate but sufficient doses for several days. In the cases of pernicious malaria, if there are not ten or twelve hours before the expected time of attack in which to secure complete cinchonism by the oral administration of the drug, it should be given subcutaneously. In order to secure its com- plete solution, acid must be added, one minim of dilute sulphuric acid to each grain of quinine usually sufficing. But this solution has the disadvantage of being irritating, and there is some danger of abscess. This risk, however, should be taken in preference to that of a severe congestive chill. The hydrobromate of quinine is especially adapted for subcutaneous use. It may be prepared according to the following formula: T? Quininae sulph 10 (gr. clx.) Acidi hydrobromici (Squibb) 4 (5 i.) Aqua? (vel spts. fru- menti) ad 30 (3 i.) The kinate and the disulphate of quinine are preferred by some for hypodermic use. The dose of quinine subcutaneously is less than by the mouth, and its action is more prompt. When for any reason neither of the foregoing methods is available, the drug may be given by the rectum in doses somewhat larger than by the mouth. For children and others with sensitive stomachs, when haste is not an especial object, quinine may be given by inunction. For this purpose an eligible preparation is the following: I? Quininae sulph. 5 (gr. lxxx.) Acid, oleic, pur 30 (5 i.) 01. olivarum 30 (5 i.) Dissolve the quinine in the acid with the aid of gentle heat. Add the oil. The solution should be clear. There is considerable choice among the various salts of quinine both as to their strength and as to their solubility. For example, the acetate contains 87 per cent, of quinine, the basic and neutral hydro- chlorate each nearly S2 per cent., the basic lactate 78, the basic hydrobromate 76, the basic sulphate 74, the neutral sulphate less than 60 per cent., while the tannate, much is favor for administration to children in the form of "chocolate quinine tablets," has only 20 per cent. The hydrochlorate is the most soluble salt, and as it is one of the richest in quinine, it is. in spite of its slightly greater cost than some others, the most eligible. The neutral hydrobromate is soluble in 6 parts of water, while the basic sulphate is soluble only in 5S1 parts of water. In old malarial cases, in many of which the liver is enlarged, we must, in order to get the full and prompt effect of quinine, preface or accompany its exhibition by the use of a mercurial, as calomel or blue pill, followed by a saline. The other alkaloids of cinchona, quinidine, chinoid- ine, c'nehonidine, and cinchonine, have some an- tiperiodic value, but are all inferior to quinine, and if used should be given in larger doses. Regarding I lie -IS J REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Antlpyrlne ,\,, f quinine, it should be said that it varies much q I only with the individual, but with the place In the tropics and in the habitat of malaria much larger doses are tolerated and arc necessary to break up a chill than in temperate climates and non-miasmatic localities. The prophylactic value of quinine against ague is even greater than its curative action. A moderate amount— as, for instance, a grain three times a .lay -may he taken constantly for years without any ill effects. This precaution is one that should he taken by every one compelled to live in a malarious country. Even in non-malarious districts persons who have contracted ague elsewhere should, afi r breaking up the chills by the antiperiodic dosi scribed above, continue with small quantities ol quinine for a fortnight or more, or better, with a full dose once a week. Next to cinchona, the most useful antiperiodic which we possess i- probably arsenic. It is to those chronic cases which nave assumed a somewhat irregu- lar type, and in which we hardly know at what time to expect a chill, that arsenic i- particularly adap It may he given in the form of Fowler's solution. beginning with 0.3 gram (n\v.) three times a day, i up to 0.5 or 0.7 or even one gram times a dav. or the arsenousacid may be given in gran- ule- of at first 0.0015 to 0.002 gram (gr ^ to^„) three times a day. pushed till the physiological effects are reached. \'\ itn arsenic we do not attempt to stop the very next paroxysm; hence it is not adapted for perm- eases. It should always be well diluted and given on a full stomach. When treatment has been delayed until the chill is actually "on," quinine is useless for that seizure. Nothing is so efficacious to check a chill actually in progress as a full dose of morphine subcutaneouslv. Chloroform is also recommended for this purpose in a of from two to four grams ( 5 ss. to i.) in sweet- ened water or mucilage. Good effects have been claimed for the administration, during the chill, of nitrite of amyl by inhalation, and nitrate or muriate of pilocarpine hypodermically. Nectandra, or bebeeru bark, has met with some ess as an antiperiodic. The alkaloid, in the form of the sulphate of beberine, contains whatever of virtue the drug possesses, and may be given in the same doses and at the same times as quinine. Warburg's Tincture, formerly in much repute, especially in India, as an antiperiodic, contains some sixty-four ingredients, of which the most active is quinine, in the proportion of ten grains to the ounce. The eucalyptus seems to possess some antiperiodic virtue. Among the peasantry of Southern Europe it has quite a reputation. Careful observation shows that in highly malarious localities it is often without it. The oil of eucalyptus in doses of 0.1 to 0.3 grain (rn_ ij. to v.), may be given, or the tincture in doses of one to two grams (nixv. to xxx.). That it is of use in the milder cases is made probable by the fact of its undoubted power as a prophylactic. Since tree was introduced into Southern Europe in 1856, its growth has much improved the health- fulness of many marshy regions. The Trappist monks devoted themselves to cultivating this tree in the most malarious regions of Italy, with the result of making places habitable that were formerly highly unhealthy. This result is now known, however, to have been due merely to the effect which the trees had in sucking up standing water, which had been a breeding place for the malaria-bearing mosquito. Charles F. Withixgton. Antipyretics. — Antipyretics are therapeutic agents or measures which are employed to lower the body temperature when it is abnormally high. As a rule they exert little or no influence upon the normal body temperature. The temperature of the body may be reduced in two way-: (1) By lessening the production of heat; and (2) by increasing the dissi- pation of leal. The production of heal may bed !: (1) By reducing the circulation; and (2) by a general lessening of the metabolism of the body. Vgents used to reduce the circulation, are; \uliinoi,\ preparations, colchicum, digitalis, trimethylamine, and veratrine: also I he appli I lips, and leeches. General lessening of the metabolism may be brought about by: Act anilide. acetphenet- idin. alcohol, antipyrine and the coal tar denvatj in general), benzoic acid, berberine, camphor, eu- calyptol, phenol, picric acid, quinine and it- alka- loid-, resorcinol, salicin, salicylic acid and the sal- icylates, salol, and thymol. The dissipal i at may be I: (1) By abstracting heat from the body; and (2) by pro- ducing pcr-piration and increasing evaporation. Heat is abstracted from the body by cold baths and sprays, cold drinks, and the application of ice or cold packs to the surface of the body. This method is the readiest, the most rapid, and probably the safest way to reduce the body temperature. Diaphoretics used for this purpose are Dover's powder, spirit of nitrous ether, acetanilide, and antipyrine. Aconite will also reduce the body temperature; so will chloral; but how many of these antipyretic- act is not known. Antipyretics as a class (particu- larly the coal-tar derivatives) are depressing, and dangerous. As in other conditions, the cause of the abnormally high temperature should be sought and, if possible, removed. R. J. E. Scott. Antipyrine. — Axtipyrixa (Y. S. P.). phenazonum ( B. P.), phenyldimethvl-isopvrazolone, C' HX.,0(CH,),. C II, or (CH 3 )N.C (CH 3 ): CH.CO.N(C.H 5 ). This is one of the earlier so-called coal-tar synthetic remedies, obtained by the action of acetyl acetic ether upon phenyl-hydrazine. It occurs in the form of a white crystalline powder or scales, of a bitterish taste, readily soluble in water (the only substance of its class except. resinol having this property), alcohol, and chloroform, and in forty parts of ether. When treated with a solution of ferric chloride it gives a deep red color. It is chemically incompatible with most substances, with some of which indeed, such as amyl nitrite and nitrous ether (when containing free nitrous acid), it forms poisonous compounds, and should therefore always be prescribed alone, or with caffeine, salicylic acid, or potassium bromide. With some substances it combines to form definite chemical compounds, such as salipyrine (antipyrine salicylate), tussol (antipyrine mandelate), hypnal (antipyrine chloral hydrate), etc. Antipyrine is analgesic, antipyretic, hemostatic, and antiseptic. It was introduced as a febrifuge, but, like other remedies of its class, was seen to possess the disadvantage of depressing the heart action and causing profuse sweating, and its greatest value was f. mud to reside in its anodyne and analgesic properties. It may be given for the relief of headache, the crises of tabes dorsalis, neuralgia, dysmenorrhea, and rheu- matic pains, in doses of gr. iv.-x. (0.25-0.6), re- peated with caution every two or four hours. In the pyrexia of pneumonia and other sthenic fevers it is sometimes useful in similar doses, but should not be continued if depression or profuse sweating occurs. Locally it is employed in four-per-cent. solution as an antiseptic and local anesthetic in acute rhinitis, pharyn- gitis, and other mucous-membrane inflammations of the upper air passages. Its hemostatic properties render it of service, applied in powder or strong solution, in epista.xis and in bleeding following the division of urethral stricture. A rash of a purplish patchy character may follow the administration of antipyrine in susceptible in- dividuals. In large doses it causes marked depres- 483 Antipyrine REFERENCE HANDBOOK OF THE MEDICAL SCIENCES sion, cyanosis, sweating, vertigo, shallow respiration and dyspnea, rapid heart action, and convulsions. These symptoms are not common after therapeutic doses, but may occur even after small doses, and caution should always be observed in its adminis- tration. The treatment of toxic symptoms caused by antipyrine consists in the application of heat to the extremities and body and in the administration of stimulants, strychnine, or atropine; inhalation of oxygen may be of service. T. L. S. Antisepsis. — See Asepsis. Antiseptics. — This term was originally applied to those means whereby putrefactive decomposition could be prevented, but has gradually acquired a much broader meaning. We now consider as antisep- tics only those agents which suppress certain functions of microorganisms, inhibiting their development but nut killing them. If the bacteria are removed from the influence of an antiseptic they will be able to resume the function of multiplication. In many instances, substances in a certain dilution act as antiseptics, but when employed in a stronger con- centration have the power of killing bacteria, that is to say, become germicides or disinfectants. There are, however, notable exceptions to this rule. A detailed discussion of the whole subject will be found under the heading Disinfectants. Ralph G. Stillman. Antiseptol is the trade name for a substance pre- pared by mixing a solution of twenty-five parts of cinchonine sulphate in 2,000 parts of water, with a solution of ten parts each of iodine and potassium iodide in 1,000 parts of water. The precipitate formed is washed and dried and constitutes a reddish or dark brown powder, without odor, almost insoluble in water and freely soluble in alcohol and chloroform. It is an odorless iodoform substitute containing fifty per cent, of iodine, and when used internally is given in dose of gr. i. to v. (0.06-0.3). Antiseptol is also cinchonine iodogallate and cinchonine herapathite, although its chemical formula is unknown. W. A. Bastedo. Antisera. — See Antitoxins. Antispasmin is a double salt of sodium salicylate and narceine-sodium, having the formula C, 3 H, 8 No s Na + 3C 6 H 4 OHCOONa. It is a reddish, slightly hygro- scopic powder, which is readily soluble in water; fifty per cent, of it consists of narceine. As an antispas- modic and sedative it is given in whooping-cough, laryngismus stridulus, chorea, asthma, etc., especially in children, and is useful in allaying irritating cough or intestinal colic in adults. On account of its affinity for moisture it is preserved with difficulty in the dry state, and therefore may well be kept in five-per-cent. solution; of this, five to eight drops are given to a child of six months, or forty drops to a child of five years; an adult may take one or two drams. W. A. Bastedo. Antispasmodics — If we are to interpret the term antispasmodic in its literal sense as a means of pre- venting spasm, nothing so completely fills the requirement as ether or chloroform, pushed to complete anesthesia. In conducting a careful phys- ical examination, especially in diseases of the abdomen or pelvis, such relaxation of spasm is often secured by anesthetizing the patient. But as ordinarily used by therapeutists the word antispasmodic is given a somewhat loose and unscientific application to a class of drugs supposed to be of special service in controlling at tacks of muscular spasm depending upon functional nervous derangement. The inappropriate- 484 ness of the name is seen from the fact that it is not alone convulsive phenomena which form indications for their use, but that they are also useful in other of the multiform manifestations of nervousness or of hysteria. The theory of their mode of action — if, indeed, any one method of action is common to all the members usually included in the class — is not sufficiently established to make any discussion of it profitable in this place. Suffice it to say that it is not impossible that at least one important action of these drugs is a local one upon the intestinal tract, where their warming and stimulating character may produce a revulsive effect. For the detailed description of the most important drugs included under this heading the reader is referred to their proper titles. To be mentioned in connection with atropine, which is the alkaloid of belladonna, is homatropine, an artificial tropeine which has been recommended as a desirable substitute for atropine as a mydriatic on the claim (not well substantiated) that it produces no increase in the intraocular tension. Belladonna has a considerable power of relaxing spasm, as, for instance, in the unstriped muscular tissue of the intestine. It and its congeners, stra- monium and hyoscyamus, are also much used in asthma, which is a disease attended by spasm of the bronchi. In the same condition opium is at times of the greatest value, the hypodermic injection of morphine alone causing relief in some asthmatic attacks. In "colic" (meaning spasm of the muscular walls of the intestine) opium is also invaluable. This drug, like the anesthetics already mentioned, while distinctly antispasmodic, has other and more important therapeutic qualities which lead to its classification in another group (see Anodynes). Scopolamine, identical with hyoscine, is of value. It has been combined with morphine, in which com- bination it must be used with care. It has also been used instead of chloral in tedious first stage of labor. It may be given hypodermically in doses of gr. -j-Jj grain. Apomorphine is sometimes employed as an anti- spasmodic in delirium tremens. It is believed by some to be efficient in quieting this mania in less than emetic doses, but is usually employed in doses of gr. ^ to T V hypodermically which not only relieve the excitement but empty the stomach as well. Among other remedies traditionally called anti- spasmodics, we have a group of animal origin, strongly odorous, but of little therapeutic value. Moschus, musk, an oily substance obtained from the preputial glands of the Thibetan musk-deer, is the only one of this class which is used to any extent. In the last stages of adynamic diseases, as typhoid fever, it is given, especially by German physicians, but rather as a forlorn hope than with real confidence. Its former use in hysteria is now quite superseded. Castorcvm, a corresponding secretion from the Castor fiber, or beaver; ambergris, a morbid product obtained from the sperm whale, and the source of the oleum suceini; and the oleum animate of Dippcl, a substance of disgusting origin and nature, obtained from "trying out" decomposing animal structures, deserve mention only as having been at some time used as antispasmodics. Another group consists of drugs of generally feeble action, but occasionally useful in infantile hysteria and allied states. Among these are humulus, hops, and its derivative, lupulin. The former, applied locally in the form of poultices or embrocations, has possibly some virtue, and the latter is somewhat more active internally. Lactucarium, derived from the garden lettuce, is even more feeble than hops, but as some persons are made drowsy by eating let- tuce, it is not impossible that lactucarium may have in certain cases a useful medicinal effect. The claims which have been made for celery as an antispasmodic and anticephalalgic do not seem to rest on reliable REFERENCE HANDBOOK OF TIIF. MEDICAL SCIENCES A III i IK]. .Ill i.^ grounds. Cimicifuga, or black snakeroot, belongs in this group. It has been chiefly used in chorea, and in full doses it has seemed to have some effect Dra- contium, the root of the "skunk cabbage," and gaU ..i ingredient with asafetida and myrrh in the la Oalbani Comp., 1". S. I'. 1880, have also had antispasmodic virtues ascribed to them, but with little reason. \\ ,■ n..u cm 1 1. ■ lo i In- group which contains the most important drugs of this class. They are three in number, viz., camphor, valerian, and asafetida. They ; ill produce a sensation of warmth in the stomach, and probably stimulate the whole alimentary canal. Hut that this is not their sole action is proved by their rioritv in certain nervous states over the essential oils and other so-called carminatives. The intestinal action of camphor makes that drug a valuable aid in the treatment of cholera and choleraic diarrhea. In the delirium of adynamic fevers and as a sedative for "nervousness" it is useful. An especially quieting influence lias been claimed for it in sexual irritation and excitement. For more distinctively hysterical symptoms, camphor is often combined with bromine in the form of bromated or monobromated camphor, which, despite? its disagreeable taste, difficult solubil- ity, and frequent tendency to cause irritation of the stomach, is considerably used for chorea, reflex con- vulsions, etc. Perhaps no drug is more generally used to combat the true hysterical convulsive seizure than valerian, and certainly in many cases it meets the indication better than almost any other agent. The fluid extract and the ammoniated tincture are among the most eligible palliatives of the hysterical attacks, sometimes a single dose serving to restore conscious- ness. For more protracted use in the countless nervous manifestations of hysteria, hypochondria, and neurasthenia, the salts of valerianic acid, notably the valerianates of zinc and of ammonium, are especially adapted, serving to control at times even i positive and conspicuous symptoms as neuralgia. Asafetida, long the synonym for what is most loathsome and offensive to the palate, acts very like valerian in the hysterical attack. The flatus which lias been rolling about in the intestine is expelled, and, as has been intimated above, there is some reason to believe that the stimulation of the intestinal mucous membrane and the revulsion so caused may, with the relief of the tympanites, play a prominent part in the alleviation of the hysterical spasm. In cases in which simulation seems to have any part in the attack, the vile taste of the drug may become of service in adding to its effectiveness. In other cases we may give the drug by enema, and its action upon the intestine and also its effect on the convulsions will be nearly the same as if it were administered by the mouth. While the above-mentioned drugs constitute the more distinctive antispasmodics, there yet remain two groups to which the term is often applied, and of which some part of the action is similar to that above described. The compound spirit of ether, Hoffman's anodyne, is very useful in controlling nervous dis- turbances, as is also the spirit of chloroform, formerly known as chloric ether. The substances from which these are derived — sulphuric ether and chloroform — may, administered internally in appropriate doses, be employed for the same purpose, although, of course, their more proper classification is among the anesthetics. The bromides of potassium, ammonium, and sodium and chloral, though in their most promi- nent action depressomotors, are yet, in moderate doses, used as antispasmodics. Finally, we have the group which includes coffee, tea. mat<5, and guarana, of all which the active principle is practically identical with caffeine. Leaving out of account the important action of this substance upon the heart and circulatory system, and limiting our attention entirely to functional nervous phenomena, we find that in migraine, which in the family of diseases is not distant of kin from hysteria, of the mo i useful remedies are caffeine and guarana. The newer analgesics of the coal-tar series, such as antipyrine, acetphenetidin, acetanilide, etc., are, many of them, constituents of unethical proprietary remedies, which as used by the public for headache and other nervous symptoms are a distinct source of danger, causing s etimes profound cyanosis with fatal re- sult. I lematopot ■phyrinuria has thu been caused. The employment of these drugs, especially as domestic ret lies, should be forbidden. Marked antispasmodic elfects, in many cases fur superior to those obtained by the above mentioned drugs, are to lie gained by the external use of water in the form of the hot bath, the warm pack, and tin; ni her devices of hydrotherapy. Moreover, the latter agency is devoid of some of I he dangerous effects nf the drugs above mentioned. Hydrotherapy is destined to supersede many of the old-time anti- spasmodics. Charles F. Withington. Antisudorifics. — Synonym, antihidrotics. A group of remedies employed to check excessive secretion from the sudoriferous glands. It includes belladonna and allied plants, agaricin, picrotoxin, mineral acids, sulphate of copper, oxide of zinc, and many other drugs which possess astringent properties. What may be termed indirect antisudorifics are creosote, sulphocarbolates, and other antiseptic remedies, also strychnine, iron, and tonics generally, which act by improving the tone of the system and overcom- ing any debility which is often the predisposing cause. Excessive sweating may occur with a marked degree of pyrexia or an entire absence of fever. It may be general or local, affecting a paralyzed limb only, or limited to the hands or feet during perfect health. (See Hyperidrosis.) That form which is of importance to the practitioner is the very profuse sweating met with in phthisis and in all forms of septic absorption. In these conditions the loss of fluid is at times enormous, and as there is also present a large amount of solids, it becomes a very exhaustive drain upon the system. This secretion is not an ordinary transudation of water in the form of serum. It is a special secretion controlled by special nerves, and any depression or paralysis of these nerves at once lessens the secretion. This is well seen in the effect of poisonous doses of belladonna, when the vasomotors are paralyzed and the flow of blood in the skin is increased, but notwithstanding this the skin remains dry on account of the sudoriferous glands being also paralyzed. The antisudorifics are useful in all forms of hyperi- drosis. Their action, however, is but the relieving of a symptom and not the cure of a disease. For- merly they were given very empirically, an immediate effect being desired, whatever the cause. With our increased knowledge of the action of toxins and the production of sepsis, not so much is expected of the drugs. More attention is given to the general health of the patient and to removing the cause of the sweat- ing. In tuberculous and septic conditions an effort is made to lessen the formation of toxins; and we also realize that the excessive sweating is an effort of nature to cast off the poisons, and unless its production is lessened much harm may arise if its excretion is suddenly checked. The most valuable of antisudor- ific drugs is belladonna and its alkaloid. One of its earliest effects is to parah'ze the secreting glands of the skin and mucous membranes, and, aside from its interfering to a slight extent with the digestion, its action is wholly favorable. The effect of belladonna is secured by the administration of atropine by the mouth, or preferably by hypodermic injection. It 485 Antisudorlfies REFERENCE HANDBOOK OF THE MEDICAL SCIENCES may be commenced in moderate doses of gr. yi^, but its full physiological action must be secured and as much as gr. .,'„ may be required. Too frequently the dose employed is insufficient. The rapidity of its action varies. Sometimes the system responds almost immediately, at other times its effect is not evident for three or four hours. Usually the effect of a full dose will last for two or three days. Local application of the ointment and liniment of bella- donna will produce the same effect, but is less under control. Hyoscyamus and its alkaloids have also the same action. Agaric acid has been used with much suc- cess in doses of gr. -fo to J. Picrotoxin has also been recommended in doses of gr. t^j to ^. Zinc oxide, gr. ij. to iv. at bedtime, and sulphate of copper, gr. ss. are very old remedies. One of the oldest remedies, and, next to belladonna, one that is the most generally employed, is the aromatic sulphuric acid. This requires to be given more continuously until it produces its astringent action. At first, ni xx. three or four times a day, should be given for two or three days, after which a single dose at bedtime will continue "the effects of the drug. The dilute phosphoric acid is also of service when administered in the same way. These acid astringents have not the same specific action as belladonna, but are probably excreted in part by the sweat glands, and during the excretion exercise their astringent action. Camphoric acid, gr. vii. to xii., has been highly recommended. Bathing the surface of the body with weak acid solutions assists in allaying perspiration and prevent- ing the "night sweats," for it is known that all acid solutions will lessen the secretion of acid-secreting glands. Dilute acetic acid, or vinegar, one table- spoonful to the pint, applied at bedtime, and in severe cases repeated a short time before the ex- pected "sweat," will allay the trouble and at the same time prove most refreshing. For local sweating of the hands or feet the general health of the patient must be attended to, after which the above drugs may be given in more moderate doses and extended over a greater period. In addition dusting powders and lotions may be used, salicylic acid five per cent, with starch and talcum, oxide of zinc, tannin. Solution of formalin ten to twenty per cent, in water or alcohol is particularly beneficial. Beaumont Small. Antitoxins; Antitoxic Sera. — The word antitoxin is at present usually restricted to substances found in the blood of animals which neutralize the toxins produced by bacterial or other cells. Other substances exist which are slightly antitoxic. These are found in old cultures, and Bolton developed them from toxins by means of electricity. An antitoxin is, to a large degree at least, specific in its effects on poisons; that is, it acts only, or at least chiefly, upon the toxins produced by" one species of organisms. Thus, a given quantity of antitoxic serum from a horse made immune to diphtheria will absolutely neutralize a number of fatal doses of diphtheria toxin, so t hat the mixture injected into an animal will prove harmless. The same antitoxic serum mixed with the toxin from tetanus bacilli will have no appreciable neutral- izing effect. In a few instances some have reported an antitoxin to have an effect on more than one toxin, but even here this effect is always much greater upon some one than upon the others. Antitoxins are present to some extent in the blood of a certain percentage of animals which have not passed through an infectious disease or been injected with bacterial or other cell poisons. For instance, li"i i usually have more or less of a substance an- titoxic to the diphtheria toxin. Thus it will require 5 c.c. of the blood of one horse to protect a 250 gram guinea-pig from ten fatal doses of diphtheria toxin, while in another j'j c.c. will suffice. The blood of these same horses may have no neutralizing effect upon tetanus toxin. Whether these antitoxic substances present in small amounts in normal blood are the same as those present in larger amount in the blood of immunized animals, we as yet do not know. Neither in their chemical nor in their physiological properties can we detect any difference. The Nature op Antitoxins. — Up to the present time we know only that they seem to have the prop- erties of globulins. If it were not for the fact that we have them present in normal blood, we might, in order to account for their specific qualities, consider them as partly satisfied combinations of globulins and specific toxins, but as they occur without the pres- ence of toxins this theory seems to be excluded. Blood from either normal or immunized animalx contains a number of globulins, and some of these, when the blood is antitoxic, prove antitoxic also. By no known method can we separate the antitoxin from all the globulin so that if antitoxin be not a globulin it is at least a substance very closely allied to it. Exactly how the antitoxins are produced we do not know, but we believe them to be cell products. Different antitoxins may be produced by different cells. A relation which exists between the amount of antitoxin in the blood of an immunized animal and the amount of globulins has been noted, in the tests of the different horses under the care of the Department of Health of the city of New York, by Atkinson. He found that the globulin increased and decreased roughly as the antitoxin increased and decreased. Antitoxins are only fairly stable substances. In sera antitoxins more or less slowly deteriorate, largely according to the conditions under which they are kept, but partly also in proportion to the abund- ance of certain blood ferments. In sterile serum, kept cold and free from access of air, antitoxins deteriorate very slowly, diminishing from ten to fifty per cent, in a year. Exposed to light, air, and slightly elevated temperature, they quickly become altered, and especially so if exposed to heat above 50° C. Exposed to 70° C. for ten minutes, a portion of the antitoxin in a solution i-< destroyed. As the antitoxins of diphtheria and tetanus have been the most studied and are by far the most im- portant of the known antitoxins, they will be con- sidered in detail as types of the others. Both of these antitoxins have the power of neutral- izing their corresponding toxins, so that when a certain amount is injected into an animal before or together with the toxin the poisonous effect of the toxin is removed. There is still some difference of opinion as to whether antitoxin acts by direct chemi- cal neutralization of the toxin or indirectly on the cells. The facts in favor of a direct action of antitox- ins upon their corresponding toxins have been briefly summarized by Cobbett as follows. 1. Certain reactions have been observed to take place between these substances outside the animal body (venom, ricin, crotin, tetanus toxin, diphtheria toxin, and their corresponding antitoxins). 2. Various attempts by filtration, chemical means, and heat to separate the toxins and antitoxins from neutral mixtures have been failures. Partial successes have, at least in some instances, been shown to de- pend upon the fact that insufficient time for the com- plete union of toxins and antitoxins was allowed, separation being no longer possible if this were granted. .;. The accuracy of the titration of toxins and an- titoxins to within one per cent, of error. 4. The fact that to save an animal from one thousand fatal doses of toxin requires little more than 1st; REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ rilitin I.- a hundred times as much antitoxin as is required to fully protect for ten fatal doses, the resistance of the animal itself accounting for the difference. ;,. Thefact |liat the potency of antitoxin is greatly Increased if it is allowed I" remain for a sufficient time in contact with the toxin at a suitable tempera- ture to allow of chemical union. On the other hand, the (■(inclusions which Buchner Rous drew from their experiments have been shown to have been based, partly at least, on a mis- eption, for they ignored the capacity of an animal to deal with a certain minimal quantity of poison, and consequently made no distinction be- tween what seemed to be a physiologically neutral and a completely neutral mixture. The facts now known, therefore, indicate clearly that the antitoxins of tetanus, diphtheria, the plague, and cholera, of snake poison, of ricin, etc., enter into direct chemical combination with their respective toxins — a combination which is, perhaps, not exactly comparable to that of an acid with an alkali; for, as we have seen, it is a much slower one, but one which possibly as Ehrlich has suggested — more closely resembles the formation of a double salt. Some facts seem to indicate that the antitoxin has a stronger affinity for toxin than the toxin has for the cells. Many points, however, are still far from clear as to the manner in which both toxins and antitoxins act. The Persistence op Antitoxin in the Blood. — About five days after the absorption of toxin has Ceased, either after a natural disease or after an arti- ficial infection, the production of antitoxin in the body stops, and the amount in the blood gradually ens, partly from its elimination by the urine, milk, and partly, perhaps,by its destruction in the blood. The blood of an animal highly immunized may retain appreciable amounts of antitoxin for from three to six months. When animals are immunized with the antitoxic sera of animals of other species, the antitoxin is much more quickly eliminated than when sera from the species are employed. For this reason the immunizing effect of sera in man against diphtheria, tetanus, and the few other infections for which we have antitoxins, is of quite short duration, much less than if antitoxins had been developed from toxins injected. Thus, immunization of a child with 1,000 units of antitoxic horse serum insures immediate safety, but only ten days of certain protection from diphtheria or tetanus. The diphtheria and tetanus antitoxins are the only two used extensively in treatment. All the other protective -era are largely bactericidal in their action and owe what value they have to this characteristic. The most important of them will be touched upon in the article on immunity, under the bactericidal prop- 5 of the blood. The use of antitoxins in the prevention and treat- ment of diphtheria and tetanus is so important that some details as to how to choose and administer the sera may be of value. All antitoxic sera must be injected subcutaneously, or intravenously, for they are only very slightly absorbed by the stomach or intestines. The sera should be clear and have no odor except in cases in which an antiseptic has been added, such as trikresol or carbolic acid. Let us now sider in detail the diphtheria antitoxic serum. The dosage is regulated by units of effect and not by weight, for we have nofr as yet absolutely isolated antitoxin. A unit is the amount of antitoxin which protects a 250-gram guinea-pig from about 100 fatal doses of diphtheria toxin. Toxins produced in differ- ent ways are found to vary in their relative toxic and neutralizing forms. In Hygienic Laboratory of the U. S. Public Health and Marine-Hospital Service sup- plies a standardized toxin to be used by the different producers. Diphtheria antitoxic serum is put up in dill, tent "grades," the lower grades having 800 to 1,000 units i n each cubic cen timet er(jf globulin solution, the higher grades having 1,400 to 2,000 units. Other things being equal, the higher grades are better and more convenient than the lower ones. Thi concentration should be of antitoxin and not of proteins, for thick sera do not, absorb as quickly as when more diluted. The Amount of Diphthebia Antitoxin to be VdMINISTJ 10 D k.ND THI \ I MBEE OF [NJECTIONS IN A. Single Case. Therei -till ome difference of opinion a ng competent observers as to the answer to the B questions. For immunization, 500 units in infants and 1,000 in adults will suffice. In treatment, our practice is the following: Cases seen early, in which the onset is mild, 2,000 units. Cases seen early, in which the onset is severe, shown either by local sign-, such as swelling, hyperemia, or the extent of the exudate, Or by constitutional symptoms, 10,000 to 20,000 units, according to severity. Cases -ecu after the disease has progressed so far that its probable local extent can be guessed, mild case-, 2,000 to 5,000 units, according to the size of the patient; moderate cases, 3,000 to 5,000 units; severe cases, showing necrotic membrane, swollen glands, or laryngeal sten- osis, 10,000 to 20,000 units. For these severe cases the antitoxin should be warmed to body heat and then injected intravenously. The effects to be expected from the antitoxin are, that the local disease should not extend, that the swelling and hyperemia should lessen and the constitu- tional symptoms abate. If twenty-four hours after the injection these changes have not begun clearly to manifest themselves, the injection of antitoxin should be repeated. The extent of the disease, rather than the size of the patient, guides the dose; still size should be considered, as the concentration in the blood is of course in proportion to the size. When antitoxin is injected subcutaneously it is absorbed very slowly. At the end of twenty-four hours not more than one- half has been absorbed. When given intravenously the whole amount becomes immediately available. Second injections are not usually required if the full sized initial dose is given. Larger amounts of serum are advised by some. There is no objection in giving more except for the expense. With the serums as now used, these large doses have produced in a small percentage very disagreeable results, namely, rashes, fever, and in a few joint inflammation. Whether some samples of serum may or may not cause, along with their beneficial effects, really serious deleterious effects, is still undetermined; but we do know that many samples of serum produce practically not even disagreeable effects. Thus. I have seen sixty cases treated, with only one rash. Serum as such is rarely given, but instead a solution of globulins. Banzhaf, Gibson and Atkinson finally succeeded in eliminating from the antitoxin all the serum constitu- ents except a portion of the globulins. Although rashes occasionally follow the injection of the anti- toxic globulins they are much less frequent than from the whole serum. The Production of Diphtheria Antitoxin for Therapeutic Purposes. — As a result of the work of years in the laboratories of the Health Department of New York City the following may be laid down as a practical method: The strongest diphtheria toxin possible should be obtained by taking a very virulent culture and grow- ing it in slightly alkaline two-per-cent. peptone bouillon. The culture, after a week's growth, is to be removed, and, after it has been tested for purity by microscopical and culture tests, is then to be rendered sterile by the addition of ten per cent, of a five-per- cent, solution of carbolic acid. On the following day the sterile culture is filtered through ordinary sterile filter paper and stored in full bottles in a cold place 4S7 Antitoxins REFERENCE HANDBOOK OF THE MEDICAL SCIENCES until needed. Its strength is then tested by giving a series of guinea-pigs carefully measured amounts. The horses used should be young, vigorous, of fair size, and absolutely healthy. A number of such horses are severally injected with an amount of toxin sufficient to kill 1,000 guinea-pigs of 250 grams weight. After from two to three days, so soon as the fever reaction has subsided, a second subcutaneous injection of a slightly larger dose is given. With the first three injections of toxin about 1,000 units of antitoxin are given. If antitoxin is not mixed with the first doses of toxin, only one-tenth of the doses advised is to be given. At intervals of from two to three days increasing injections of pure toxin are made, until, at the end of two months, from ten to twenty times the original amount is given. There is absolutely no way of judging which horses will produce the highest grades of antitoxin. Upon a very rough estimate I may say that those horses which are extremely sensitive and those which react hardly at all are the poorest, but even here there are exceptions. The only way, therefore, is at the end of six weeks or two months to bleed the horses and test their serum. If only high-grade serum is wanted, all horses that give less than 150 units per cubic centimeter are discarded. If moderate grades only are desired, all that yield 100 units may be retained. The retained horses receive steadily increasing doses, the rapidity of the increase and the interval of time between the doses (three days to one week) depending somewhat on the reaction following the injection, an elevation of temperature of more than 3° F. being undesirable. At the end of three months the antitoxic serum of all the horses should contain over 200 units, and, in about ten per cent., as much as 600 units, in each cubic centimeter. Very few horses ever give above 1,000 units, and none so far has given as much as 2,000 units per cubic centimeter. The very best horses continue to furnish blood containing a large amount of antitoxin for several months, and then, in spite of increasing doses of toxin, the amount of antitoxin gradually decreases. If every nine months an interval of three months' freedom from inoculations is given, the best horses furnish high-grade serum for from two to four years. The toxin injected at one time should be divided into five or six portions so as to reach more tissue and lessen the liability to abscess. The Production of Tetanus Antitoxin. — The tetanus antitoxin is developed in the same manner as the diphtheria antitoxin — by inoculating the tetanus toxin in increasing doses into horses. The toxin is produced in bouillon cultures grown anaero- bically. After ten or fifteen days the culture fluid is filtered through porcelain, and the germ-free filtrate is used for the inoculations. The horses receive 0.5 c.c. as the initial dose of a toxin of which 1 c.c. kills 250.000 grams of guinea-pigs, and along with this a sufficient amount of antitoxin to neu- tralize it. The antitoxin is added to the first few- doses. In five days this dose is doubled, and then every five to seven days larger amounts are given. The dose is increased as rapidly as the horses can stand it, until they support 700 to S00 c.c. or more at a single injection. After some months of this treatment the blood of the horse contains the anti- toxin in sufficient amount for therapeutic use. When the animals' temperatures are normal and they have recovered from the dose of toxin last- given, they are bled into sterile flasks and the serum collected. Technique op Testing Tetanus Antitoxic Serum for Value in Antitoxin. — Tetanus anti- toxin is tested exactly in the same manner as diph- theria antitoxin, except that the unit of measure is different. A unit by the U. S. standard is the amount of antitoxin which will neutralize 1,000 fatal doses 488 of a standard tetanus toxin. A 350-gram guinea- pig is used as the test animal. A unit in the German standard is the amount of antitoxin needed to neu- tralize 4,500,000 fatal doses of toxin for 1 gram of white mouse. In the French method the amount of antitoxin which is required to protect a mouse from a dose of toxin sufficient to kill in four days is deter- mined, and the strength of the antitoxin is stated by determining the amount of serum required to protect 1 gram of animal. If 0.001 c.c. protected a 10-gram mouse, the strength of that serum would be 1 to lo.ooo. Guinea-pigs are frequently used in place of mice. Knorr's method of preserving toxin is by precipitating it with saturated ammonium sulphate and drying and preserving the precipitate in sealed tubes. As required, it is dissolved in ten-per-cent. salt solution, as above stated. For small testing stations the best way is to obtain some freshly stand- ardized antitoxin and compare serums with this. The Dosage of Tetanus Antitoxin. — For im- munization, one dose of 1,500 units U. S. standard is given. This will suffice unless the danger seems- great, when the injection is repeated at the end of a week. For treatment, an intravenous injection of 15.000 to 20,000 units should be given, according to the severity of the case. Not a moment's unneces- sary delay should be allowed. In the gravest cases ao curative effect will be noticed from the use of the serum, but in many moderately severe cases it is very beneficial. The symptoms cease to grow worse and then gradually lessen. It is sometimes injected into the spinal canal, the lateral ventricles, or even into the brain substance. Both the theoretical rea- sons for, and the actual results obtained from, this method of treatment are open to criticism. The first dose, in severe cases, should be given intra- venously, but if for any reason the physician hesitates to give it in this way it should be given subeutane- ously, rather than allow of delay. It is well to give 5,000 to 10,000 units daily until the symptoms markedly abate so as to keep up the antitoxin con- tent of the blood. William H. Park. Antitrypsin. — Blood serum contains a substance, called antitrypsin, which is able to neutralize the action of trypsin. The expression of the quantity of antitrypsin thus contained is called the antitryptie index or titer of the serum. There are two methods for the determination of this index. One, that of Jochmann and M tiller, depends upon the digestive action of trypsin on serum albumin. Loefner's blood serum plates are used and the time necessary is about twenty-four hours. This method will give results of only relative value. The incubation is carried out at 55° C, which is higher than the optimum tempera- ture for tryptic action. The variability of the reac- tion and composition of the serum, the method of measurement by loopfuls, and the possibility of bacterial contamination, all may prove sources of error. The other method, introduced by Gross and Fuld, is much more exact. It is based upon the diges- tion of a clear casein solution and the precipitation by acid of any casein remaining undigested at the end of the period of incubation. Citron thus de- scribes the performance of the test. The casein solution is made up by dissolving one gram of casein in 100 c.c. of A'/ 10(decinormal solution) NaOH, neutralizing with A'/iO HC1, using litmus, and diluting to 500 c.c. with physiological salt solution. The trypsin solution is prepared by dissolving 0.5 gm. of trypsin in 50 c.c. of NaCl and 0.05 c.c. of normal sodium hydrate solution and diluting with physiolog- ical salt solution up to 500 c.c. The acid solution consists of 5 c.c. of acetic acid with 45 c.c of alcohol and 50 c.c. of water. The trypsin solution is first titrated. "Gradually REFERENCE EANDBOOK "1 THE MEDICAL SCIENCES increasing amounts of trypsin (from 0.1 to 0.6 c.c. are placed into six test-tubes and to each 2.0 <■.<■. oi casein solution is added. These tubes are placed In an incubator at 37 c C. for one-half hour, and then several drops of acid soution are placed into each tube. The first tube, and all of those above it that n't. iain absolutely clear, contain enough trypsin fully i" digest the 2.0 c.c. of casein." For the test Itself: "Into each of eighl to ten test-tubes, are placed 2 c.c. of the casein solutionand 0.5 c.c. of a two-per- cent, dilution of the serum for examination; to these is next added the trypsin solution in successively increas- ing amounts, beginning with the smallest quantity which in the first part of the test was sufficient com- pletely to digest the given amount of casein. Salt solution is then added to each of the test-tubes so that all con lain an equal quantity of fluid, and the mixtures arc placed into an incubator at 37° C. for one-half hour. At the end of this time, several drops of the acid arc added to each tube. Those tubes which become cloudy or -how a precipitate, designate the amounts vpsin solution which have been neutralized by the C. of diluted serum." The quantity of trypsin solution in the first tube to remain clear is considered the antitryptic titer of the serum. That is. if the tubes containing 0.4, 0.5, and 0.6 c.c. of the trypsin solution yield a precipitate with the acid and those with 0.7 and 0.8 c.o. remain clear, the antitryptic index of the serum is 0.7. The test has a certain amount of diagnostic value. The antitryptic index is increased in from seventy to ninety-five per cent, of patients suffering with cancer, also frequently in acute infections, in chronic Infections, as tuberculosis, in diabetes, severe anemias, and in Graves' disease. It has also been noted in infants on the inauguration of artificial feeding and in pregnant women at the onset of labor. It evi- dently occurs in too many conditions to have the value of a specific symptom, but on the other hand it has a distinct negative value. A low index, for instance would be a good argument against the diagnosis of cancer. The nature of antitrypsin is but little understood. It is probably not a highly .specific immune body, but on the other hand it is almost certainly not a non- ific antiferment. It will act only in the presence of lipoids. Weil concludes that "the antitryptic function is exercised by an albuminous substance, thermolabile, indeed, like the true antibodies, but differing essentially from these in the lack of speci- ficity." The normal antitrypsin probably is entirely distinct from that produced in the body following the injection of trypsin. The theory of its origin is that it is produced by the body, stimulated to that effect by the presence in the blood of a certain amount of trypsin, which latter is, in part at least, a secretion of the polynuclear leucocytes. In fact, in infections there is a definite relation between the antitryptic index and the polynuclear leucocytosis. In cancer this ferment may very conceivably be produced by the cancer cells. At the present time, however, the proved facts as to the chemical and biological nature of antitrypsin are so few that no definite statements can be made concerning them. Ralph G. Stillman. Anuria. — By this term (derived from a-privative and oipon, urine) is understood a total suppression of the secretion of urine. It is to be distinguished from retention of urine, in which the kidneys are performing their function, but through atony of the bladder, spasm of the vesical sphincter, enlarged prostate, or calculous impaction or stricture of the ureters or urethra, no urine is passed; and from oliguria (iklyos, little, and ofrpov, urine) in which the secretion is greatly diminished, though not entirely suppressed, the very -mall amount formed being retained for a long time in the bladder until this viscus is sufficiently distended to excite the urinary reflex. Anuria occurs rarely in uremic attacks accompanying acute nephritis, in conditions in which there is extreme loss of' fluids through the other emunctories, as in cholera, colliquative diarrhea, profuse vomiting, etc.. and sometimes in hysteria. ahus. Diseases of the. See R ' Anus, !>.■■■ Anytin i- a derivative of ichthyol introduce, 1 by TJnna in dermatological practice. It is a thirty-three- per-cent. aqueous solution of sulphoichthyolic acid and the aromatic oily sulpho-compound contained in ichthyol. Dark brown in color, if contains l(i..j per cent, of sulphur and 4.5 per cent, of ammonium. It is decomposed by acids and strong alkalies, and possesses the peculiar property of rendering such sub-tances as phenol, guaiacol, cresol, camphor, etc., freely soluble in water. These solutions are called "anytols" and promise to be valuable additions to our antiseptic materia medica. Koelzer used a 7.5-per-cent. aqueous solution of metacresol anytol (metacresol, forty per cent.) in erysipelas. By painting it on frequently over an area extending some- what beyond the inflammation he obtained a good result in every case. These anytols, especially those of phenol and cresol, may be used in five- to ten-per- cent, dilution for disinfection of the hands or for vaginal or intrauterine douches. They then have much the same effect as creolin. Anytin itself is capable of setting up an active dermatitis, but diluted to ten per cent, it is very useful in chronic eczema, sunburn, ami ivy poison- ins. It is stated to be directly antagonistic to the diphtheria bacillus. W. A. Bastedo. Aorta. — From the Greek, aoprr/, from aeipeh, to lift, to carry. Synonyms. — Arteria magna (Harvey); haemal axis lOwen). French, aorte; German,; grosse Schlagarlcr. Originally, in the plural, aortae iaoprai) signified the bronchial tubes (Hippocrates). Definition - .- — The main trunk (single in mammals and birds, double in cephalopods and most reptiles, triple in the crustaceans) of the systemic arterial system, by means of which the oxygenized blood is carried to all parts of the body. Embryology. — According to Gibson, "the single median tube," which is seen at one stage in the development of the vascular apparatus, begins to pulsate before the appearance of either muscular or nervous elements. "The heart movements must be due to some as yet unknown indwelling property of the embryonic heart tissue." In the development of the embryo there are two primitive aorta 1 . These unite early, and to them four lateral pairs are succes- sively added, and all develop into the artery seen at birth — the aorta and its branches. Anatomy. — The aorta, although the main arterial trunk, is at its commencement generally a little smaller than the pulmonary artery, but in the aged it is usually slightly larger than that vessel. Its position, like that of other arteries, is protected in proportion to its importance. It takes its origin from the upper part of the left ventricle, extending upward and to the left for a short distance; then curving over the root of the left lung, it descends in front of the spinal column, passing through the aortic opening, hiatus aorticus, which is in the middle line behind the diaphragm, and which also transmits the vena azy- gos major, the thoracic duct, and occasionally the left sympathetic nerve. The vessel descends to the left side of the fourth lumbar vertebra, where it termi- nates, dividing into the right and left common iliac 4S9 Aorta REFERENCE HANDBOOK OF THE MEDICAL SCIENCES arteries. In its course it gradually decreases in size from twenty-eight to seventeen millimeters, giving off at different points branches of varying caliber. Quain divides this artery into the ascending aorta, the part within the pericardium; the arch, that part extending backward from the pericardial limit to the spine at the lower margin of the fourth thoracic verte- bra; the descending thoracic aorta, from this point to the diaphragm, and the abdominal aorta, the part below the diaphragm. This method of division is founded on the fact that the first part is intrapericardial and has its origin from the fetal aortic bulb; while the third part of that section, which was formerly known as the arch, does not differ in relation, direction, or origin from the rest of the descending portion. The 2 3 4 5 678 9 10 11 12 13 Fig. 257. — Anterior View of the Great Vessels of the Heart. (From His's "Handatlas der Anatomie des Mensehen.") 1. First rib; 2, subclavian vein; 3. subclavian artery; 4, internal jugular vein; 5, right branch of pulmonary artery; 6, vena azygos; 7. inferior thyroid vein; 8, left innominate vein; 9, trachea; 10, arch of aorta; 11, ductus arteriosus; 12, left pulmonary artery; 13, subclavian vein; 14, right lung; 15, right pulmonary veins; 1»>, vena cava superior; 17, left atrium; IS, ascending aorta; 19, pulmonary artery; 20, left pulmonary veins; 21, left lung. older anatomists treated the arch as consisting of three parts — the ascending, transverse, and descending, and comprising that part of the artery found between its ventricular origin and the lower border of the fifth dorsal vertebra. This latter division seems far less logical than the former according to the reasons ju-t given. The first parts of both the aorta and the pulmonary artery are regarded embryologieally as parts of the heart. Ascending Aorta. — The ascending aorta springs from the upper and fore part of the left ventricle on a level with the lower border of the third costal cartilage behind the left half of the sternum. It passes up- ward, forward, and to the right in a line with the heart's axis till it reaches the upper border of the sternum, at which point its direction changes and the arch begins. The ascending aorta measures about two inches or two inches and a quarter in length, and it curves upward, backward, and to the left. Just ab.,\ ,■ its origin this part of the aorta shows externally three -mall dilatations of about the same size, known 490 as the sinuses of the aorta or sinusi s of Valsalva. ( fne of these sinuses is anterior, the other two posterior. The anterior and left posterior give origin to the two coronary arteries of the heart. Opposite to these three sinuses are the semilunar valves. A cross section of the vessel at this point is rather triangular in form, while below the valves it is circular. At the commencement of the arch and along the right side of the ascending aorta there is generally found another bulging, the great sinus of the aorta. Now and then this sinus is not present. It is seen more distinctly in the aged. The fibrous pericardium embraces the whole length of the ascending aorta, while a tube of serous membrane extends up from the cardiac surface to invest this vessel together with the pulmonary artery, except where they are in contact with each other. Relations.- — At its commencement the ascending aorta is covered anteriorly by the pulmonary artery and the right auricular appendix. Higher up, the directions of these vessels diverge, the aorta passing forward and to the right and the pulmonary artery backward and to the left. At this point the aorta closely approaches the sternum, being separated from it, however, by the pericardium, the right pleura, the narrow part of the anterior mediastinum, the anterior edge of the right lung, besides a little fat and areolar tissue, as well as the remains of the thymus gland. Posteriorly are the left cardiac auricle and the right pulmonary artery. At its right are the right auricle and the superior vena cava. On the left is the main pulmonary artery. Branches. — The ascending aorta has two branches only, the right and left coronary arteries. These vessels, relatively small, spring generally from that part of the vessel which is just above the free margin of the semilunar valves, in the upper part of the two sin- uses of Valsalva, and they supply the heart. The right coronary artery is about the size of a crow 's quill, while the left is somewhat larger. Variations. — The ascending aorta and pulmonary artery may be transposed, i.e. the former may rise from the right ventricle and the pulmonary artery from the left. There may be a communication be- t w cen these two arteries by abnormal openings. One may be wholly or partly obliterated, while the other selves as a passageway for the blood of both by means of communications between them. There is now and then seen one simple tube connected with a simple heart like that in fishes. , Sometimes the coro- nary vessels arise by a common trunk, or at times from the same sinus of Valsalva. As many as four arteries have been observed, in which case the sup- plementary vessels are smaller than normal and play the part of branches of the main coronary trunk, near which they take their origin. An extra coro- nary has even had its origin in the pulmonary artery. When one of the arteries is unusually small, the other is correspondingly large and supplies a greater area, especially at the back of the heart. Arch of the Aohta. — The arch or transverse aorta begins at the upper margin of the second right costal cartilage at the right border of the sternum and arches around the trachea, in its course passing upward, backward, and to the left of the fourth thoracic vertebra. At this point it passes downward, and at the inferior margin of this vertebra the tho- racic aorta begins. The arch at its superior border is generally about an inch below the upper margin of the sterum in the median plane. Relations. — The arch of the aorta is situated in the superior mediastinum, and is covered in front by the pleurae and lungs, and the fatty remnant of the thymus gland. ()n the left it is crossed by the left pneumogastric and phrenic and the superior cardiac branches of the left symphathetic nerve and by the left superior intercostal vein, while the left recurrent REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aorta laryngeal benda upward beneath it. Posteriorly and to the right lie the trachea, the deep cardiac plexus, the lefl recurrent laryngeal, the esophagus, the tho- racic duct, and the body of the fourth dorsal verte- bra. The anterior part of the upper margin of the arch is in contact with the left innominate vein, and gives a to the large arteries— innominate, left caro- tid, and left subclavian —which supply the head and upper limbs. The border is just above the left bron- chus and the bifurcation of the pulmonary artery. and is joined with the left branch of that vessel a fibrous cord, representing the remains of the ductus arteriosus, which is connected with the aorta just beyond the origin of the left subclavian. Be- tween the arch and i lie bifurcation of the pulmonary artery are found the superficial cardiac plexus and a few large bronchial lymphatic glands. To its infe- rior, anterior surface the fibrous pericardium is at- tached. After giving off its branches, the arch is re- i i i : e to some extent (23 mm.). There is 12 .11 —10 8 Fig. 258. — Arch of the Aorta with its Branches (anterior and from the left). After a plaster-of-Paris cast. (From His 's " Hand- ler Anatomie des Menschen," Band ii., S. 387.) 1, Right subclavian artery; 2, right common carotid; 3, innominate artery; 4, arch of aorta; 5, ascending aorta; 6, bulbus aorta-; 7, right coronary artery; s. sinuses of the ai irta ( Valsalva); 9, left coronary artery; 10, thoracic aorta; 11, aortic spindle; 12, aortic isthmus; 13, left common carotid; 14, left subclavian artery. often seen at that point where the ductus arteriosus is attached, a constricted part, which is called the aortic isthmus. The isthmus is far more marked in the fetus from the expan-ion caused by the open- ing of the ductus arteriosus. Beyond comes a fusi- form dilatation reaching to the thoracic and called the aortic spindle of His. Branches. — The aortic arch has three branches springing from its upper surface — the innominate or brachiocephalic artery, the left common carotid, and the left subclavian. The left carotid and the in- nominate arteries are generally nearer together than the left carotid and the left subclavian. These ves- sels supply the head, neck, upper extremities, and part of the thorax. I arialions. — The upper limit of the aorta may be found in some subjects as high as the third thoracic bra, at the level of the top of the sternum, while in others it is as low as the fifth thoracic. Sometimes there is complete lateral transposition of the aortic arch and pulmonary artery together with the great veins and the divisions of the heart (dextrocardia). This abnormality may be confined to these parts or may embrace all the viscera (situs inversus). The aortic arch has been observed to be completely double. It has also been seen to pass to the right of the trachea and esophagus instead of t.. the left, and to continue its downward ci 'he riL'ln 9ide mI' the pine.. I" 'his case the three branches h an arrangement the reverse of the usual Variations in the number ami position of the branches of the arch are frequent. There may be only one trunk, or there may be fj i i\ inclu Descending Thoracic Unn. - At the termina- tion of the arch, at the lower border of the fourth thoracic vertebra, the d< cending aorta begins at d continues down along the -pine to the fourth lumbar vertebra, where it divides into the two common iliac arteries. Its direction is not vertical, for as it rests against the spine ii rily follows the spi- nal curve . being concave forward in the dorsal region and convex forward in the lumbar, As it- com- mencement is to the left of the spine and its termina- tion nearly in the median line, its general direction throughout its whole length is inward, this being more marked in its upper part. The lower limit of the thoracic aorta is the hiatus aorticus at the level of the diaphragm. This part of the aorta is from seven to eight inches long and is contained in the back part of the posterior mediastinum, where it rests against the spine. Its branches are small, and equently its diameter is little diminished (from 23 to 21 mm.). Branches. — The branches of the descending thoracic aorta, though numerous, are small. They arc the pericardial, bronchial, esophageal, posterior mediastinal, and intercostal. Variations. — Now and then an obliteration of the aorta at the point of junction of the arch and thoracic portion is observed just below the connection between the ductus arteriosus and the arch. This condition, known as coarctation of the thoracic aorta, results in the establishment of an interesting collat- eral circulation. Xot infrequently variations in the number and position of the branches of this section of the aorta are observed. Abdominal Aorta. — This name is given to the vessel between the diaphragm and its bifurcation into the two common iliac arteries. In relation to the spinal column it begins about the lower margin of the last thoracic vertebra and ends at a point about the middle of the fourth lumbar vertebra, most g inerally slightly to the left, sometimes almost exactly in the median line, at other times slightly to the right. This point almost corresponds to the level of a line drawn between the two iliac crests or to a point just below and to the left of the umbilicus. In length it is about five inches. As its branches are both numerous and large, its size rapidly di- minishes. As mentioned before, its curve as it rests against the vertebrae has its convexity forward, being most prominent at the third lumbar vertebra, slightly above and to the left of the umbilicus. Relations. — Anterior to the abdominal aorta are the lesser omentum and stomach, the solar plexus, splenic vein, pancreas, left renal vein, transverse duodenum, mesentery, aortic plexus, peritoneum, lymphatic vessels and glands, and dense areolar tissue; posterior to it are the bodies of the vertebrae and the left lumbar veins, the thoracic duct, and the cisterna (receptaculum) chyli. On the right are the inferior vena cava, right crus of the diaphragm, vena azygos (major), thoracic duct, and right semilunar ganglion. On the left are the sympathetic nerve and the left semilunar ganglion. Branches. — These may be classified under two heads: (1) Visceral — celiac axis (gastric, hepatic, splenic), superior mesenteric, inferior mesenteric, suprarenal, renal, and spermatic or ovarian. i2) Parietal — phrenic, lumbar, and sacra media. The branches of the aorta mostly pass off at right angles. Variations. — Instances are known in which the aorta 491 Aorta REFERENCE HANDBOOK OF THE MEDICAL SCIENCES | — -16 — 15 is divided by a septum for either a part or the whole of its course, so that two closely united tubes are the resull. Sometimes this condition has a pathological foundation, at other times M#>| a . 21 it is due to an embryological defect in the fusion of the ' 20 double fetal aorta. The 19 vessel has been known, as i S in certain quadrupeds, to 1 7 divide into an ascending and a descending branch, the former subdividing into three trunks to supply the head and upper extremities. The abdominal aorta may vary in position and extent. Its lower limit may vary to the depth of a lumbar verte- 14 bra, so that its bifurcation may take place at the third, or even lower, at the fifth. 13 Its deviation from the normal position with refer- ence to the vertebral column is generally due to patho- logical changes rather than to congenital causes. Quain speaks of two cases of a large pulmonary branch springing from the aorta very near the celiac axis, which, after having passed upward through the esoph- ageal foramen in the dia- Chragm, separated into two ranches and entered the lungs near their bases. Bal- four, in writing of the simu- lation of aneurysm by mal- position of the aorta due to rickets, says: "In rickety chests the aorta may be so deflected, without any marked dila.tation, as to make its pulsation visible either to the right or left of the sternum, and so to sim- ulate an aneurysm. It is of even greater consequence to have proof that in certain comparatively rare cases a similar abnormal pulsation may be due to a trifling divergence from the normal course of the vessel itself, apart from any marked change in the bony skeleton. But we must never forget that aortic aneurysm may coexist with malformation of the thorax with or with- out scoliosis, and whatever may be the condition of the skeleton, any abnor- mal pulsation must be care- fully considered from every point of view before we are able to give any defi- nite opinion as to what it really is." Virchow has pointed out the relation of the reduction in size of the aorta to chlorosis, and he named the condition aorta chlorotica. Con- genital stenosis of the aorta is seldom seen. Rosen- Bach Iris noted this condition found together with hypert rophy of the heart. It may cause sudden death, and when it is present, otherwise unimportant affections may assume a grave aspect, from sudden untoward cardiac symptoms. In congenital stenosis Fig. 259. — View of the Thoracic and Abdominal Aorta. (From Joessel- Waldeyer: " Lehrbuch der Topographiseh - Chirurgi- schen Anatomic ") 1. Right common carotid; 2, innomi- nate artery; 3, right sub- clavian artery; 4, right lymphatic duct; 5, right innominate artery; 6, su- perior vena cava; 7, pos- terior intercostal glands; 8, vena azygos; 9, inferior vena cava; 10, right lumbar lymphatic duct; 11, left lumbar lymphatic duct; 12, receptaculum chyli; 13, thoracic duct; 14, posterior intercostal glands; 15, aorta; 1G, left innominate vein; 17, left subclavian vein; IS, left ■subclavian artery; 19, mouth of thoracic duct; 20, internal jugular vein; 21, left common carotid. of the aortic system, a striking characteristic is the continuous subnormal temperature present in infec- tious diseases which normally show a high temper- ature. In women this condition is generally asso- ciated with infantile uterus and other signs of ar- rested development. Structure. — The aorta is very strong and elastic and is enclosed, like most other arteries, in a sheath, which has more connective than yellow elastic tissue, so that, when cut, the vessel shrinks within the sheath. It is composed of three coats — (1) tunica Ultima; (2) tunica media; (3) tunica adventitia, The internal coat, smooth and offering but little, if any, resistance to the blood, consists of three layers (a) Epithelial layer or arterial endothelium. This is made up chiefly of irregular, flat, polygonal cells with round or oval nuclei with nucleoli. (6) Sub- epithelial layer, which is well marked and consists of numerous anastomosing cells resting in a delicately fibrillated ground work of connective tissue. There are, besides, elastic fibers which are in connection with the next layer, (c) Elastic layer, which forms the principal part of this inner coat. Sometimes this network assumes characteristics which have caused it to be designated as the "perforated" or "fenes- trated" membrane of Henle. At times it is rep- resented by a longitudinal network of fibers. The middle coat is muscular, consisting of bundles of plain muscle fibers, which are disposed circularly around the vessel, although not forming a complete ring. These fibers contract and relax, thus changing the caliber of the vessel. Elastic fibers are also found well developed in this tunic, and there is also considerable connective tissue. This coat is thicker than the corresponding coat in other arteries. It has also relatively more elastic tissue and less muscular tissue than is found in other arteries. The external coat consists of white connective tissue and elastic fibers. The connective-tissue bundles run chiefly diagonally around the vessel and connect it with its sheath. This is the strongest and densest coat. Vessels and Nerves. — Both small arteries and veins (xmsa vasorum) ramify in the external coat of the aorta. They serve as nutrient vessels. Ranvier states that in health in the human subject they never penetrate to the middle coat. The inner coat is thought to be nourished by the blood circulating through it. Alt hough the aorta is supplied by nerves, it is insensi- ble when in a healthy condition. These nerves are chiefly non-medullated. The finer branches are dis- tributed chiefly to the muscular tissue of the middle coat. The aorta is supplied by both vasoconstrictor and vasodilator fibers. Nerve plexuses are formed around the vessel. Physiology.- — The second heart sound, short and sharp, occurs just at the closure of the two semilunar valves, that is, immediately after the end of ventric- ular systole. This sound is best heard over the second right costal cartilage close by its junction with the sternum. At this point the aortic arch is nearest to the surface, and here sounds generated at the aortic orifice are best transmitted. The sound is due to the vibrations of the semilunar valves which are made tense by their sudden closure. The sound is not exclusively of aortic origin as is instanced in those cases in which the action of the semilunar valves on the two sides of the heart is not absolutely simultaneous. For then the sound is double ("reduplicated second sound"), one due to the aorta, the other to the pulmonary artery. A murmur may replace the normal sound when the semilunar veins are diseased. If the closure of pulmonary and aortic valves were absolutely synchronous the second sound would be shorter and sharper. But due doubtless to local pressure variations that sometimes occur in the aorta and pulmonary arteries, the closure of one 492 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Aorta, Diseases <»f valve may lake place just a trifle earlier than thai df the others. The sound is increased by the trem- bling of the blood column set in vibration by the ven- tricular systole and by the closure of the valves on the sudden passive recoil of the arterial walls. Sudden relaxation follows contraction of the ven- tricles, intraventricular pressure falls. The pres- sure of the blood column as it tries to regurgitate closes the semilunar valves, the central orifice is closed by the corpora Arantii, and both aorta and pulmonary artery are cut oil from the heart. By means of a pair of elastic manometers or by the differential manometer the pressure-curve oi the aorta may !»■ compared with thai of the left ventricle and thus may be determined the instant at which the .semilunar valves open and close. Tin closure of these valves is estimated to occur at a period corresponding to a point on the upper portion of the descending limb of the intraventricular curve. Clinically speaking, the semilunar valves may be said to close "0.03 second before the bottom of the aortic notch in sphygmographic tracings from (he carotid, this being approximately the average time taken by the pulse-wave in traveling from the aorta in the carotid." At the abrupt end of systole when the ventricular outflow ceases, the aortic blood col- umn continues to move on in accordance with the law of inertia. As the pressure diminishes there is a recoil of the aortic walls behind this blood column • just as a negative wave is set up in the central end of the elastic tube when the stroke of the pump is over." Now before the semilunar valves are com- pletely closed the blood is forced back against them under the combined influence of lower pressure from relaxation of the ventricular muscle and diminished pressure in the beginning of the aorta. The valves are ton I'd slightly into the ventricular cavity and a neg- ative wave — "a wave of diminished pressure, rep- resented in the pulse-curve by the 'aortic notch' — travels out toward the periphery." A rebound quickly follows in this elastic system and "the re- coiling blood meets the closed semilunar valves." Again the aorta expands; this expansion spreads throughout the arteries and is known as the dicrotic elevation. When the blood pressure within the contracting ventricles exceeds that in the aorta and pulmonary artery respectively, the closed semilunar valves are burst open and the oncoming blood torrent is forced from the ventricles into these arteries. In other words, the valves open when the pressure below becomes greater than that in the arteries. With the distention of the great arteries the sinuses of Val- salva become filled. At the completion of ventricular systole when intraventricular pressure ceases to in- crease, the passive recoil of the distended walls of the arteries forces more blood into the sinuses, thus pushing together the cusps of the semilunar valves, and aided by the corpora Arantii they entirely ob- literate the openings. In regard to the relation between respiration and blood pressure, it may be said briefly that unless the respiratory movements are very shallow a record of blood pressure gives a tracing showing waves that are synchronous with the respiratory move- ments. During inspiration the aortic pressure rises. This is due to the larger output of blood from the heart. During expiration, on the other hand, the reverse occurs. The arteries are always somewhat distended with blood but with each cardiac systole from two to four ounces of additional blood are suddenly forced into the already distended aorta. With ventricular diastole the aorta recoils, so forcing the blood for- wardin a steady stream. But this arterial contrac- tion is no more powerful than the force exerted by the heart in distending the artery. Consequently the force propelling the blood must be referred to the heart. The extra aortic distention due to ventric- ular systole gives rise lo a v\ a \ e in the blood which is transmitted throughout the arterial tubes. This wave as felt in uperficial arteries is known a- the pulse. The pulse is merely a wave in the steady stream of blood, for tl (foci of an ela tie tube on an intermittent Bow of Quid is to converi it practi- cally into a continuous stream. The average bio. id pressure in the aorta is about l"'ii millimetei Emma K. Wai k i r Aorta. Diseases of the. — Congenital Am tions: (1) Defects «./' Me Aortic Septum. — These result from failure in the division of the primitive aorta, into its two daughter vessels, the aorta and I he pulmonary artery. In both its complete and incomplete forms, this a i aly is rare. The complete defect known as persistent truncus arteriosus may be associated with absence ..I I he cardiac sept uin, but in all cases this sepi urn is deficient. The truncus may in Hie latter case override the septum, receiving blood from the two ventricles, or may spring entirely from the right side, in which case the blood from the left enters through the septal delect. The pulmonary blood-supply may arise 'near the origin of the main trunk or may come off at the site of the ductus arteriosus. Partial Defect of the Aortic Septum. — This may take the form of an opening between the aorta and pulmonary artery just beyond the origins of the two vessels, or a communication may occur between the aorta and the conus arteriosus. (2) Transposition of Aorta and Pulmonary Artery. — This, according to Abbott after Rokitansky, may result from alteration in the direction of the aortic septum, which alteration may give rise to a number of varieties of transposition. In the complete form the aorta arises from the right and the pulmonary artery from the left ventricle. Both vessels may also arise from one ventricle, right or left, or again both may arise transposed from a common ventricle. In the complete form of transposition, the cir- culatory embarrassment may be understood when it is seen that venous blood from the right heart passes to the body by the aorta and the aerated blood passes from the left heart to the lungs by the pulmonary artery. Fortunately there is nearly always an associated defect such as a patent foramen ovale or ductus arteriosus which allows of mixing of the bloods. Cyanosis appears usually within a few weeks of birth. Clubbing of the fingers is usual. The cardiac signs are inconstant and the majority of cases die before the second year, though some have reached adult life. (3) Congenital Narrowing of the Aorta. — This may be (a) Subaortic, in which a ring-like thickening occurs just below the valves which becomes the seat of a chronic inflammation which results in still greater constriction. (6) Stenosis of the orifice is very rare and is ascribed to fetal endocarditis. (r) Coarctation, occurring at the isthmus near the opening of the ductus arteriosus, may be in one form developmental, in the other or adult type an abrupt strangling of the aorta by the presence in its wall of fibers similar to those in the ductus itself, which tends to contract after its function has ceased. In this type is seen the excessive development of the cephalic vessels and atrophy of those in the lower part of the body with a consequent extensive collat- eral circulation between them. (4) Hypoplasia of the Aorta. — This affection, in which the vessel and its branches are small of caliber 493 Aorta, Diseases of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES and thin of wall, was connected by Virchow with chlorosis and by others with a tendency toward tu- berculosis and poor resistance to other infections. Cases of death from cardiac disease with this lesion as a cause have also been reported. On the other hand, Suter, from measurements of 2,719 cases, considers that hypoplasia as such has no causal relation to these affections. (5) Double Aortic Arch. — This rare anomaly con- sists of the division of the main aortic trunk into two branches which surround the trachea. The posterior branch is regarded as the fourth right arch and the anterior as the fourth left arch, which join to form the descending aorta in the am- phibia (Abbott). Aortitis. — That such a condition as aortitis does ex- ist is nut debatable, but concerning the place it should hold as a clinical entity there is wide difference of opinion, English and German writers looking upon it witli distant politeness, while the French embrace it as an old friend. A natural conclusion is that on the one hand a real condition may often be overlooked, or its symptoms attributed to some other cause, while on the other hand the early stages of a purely regressive process may be classed as an inflammation. French writers divide aortitis into three groups: (a) with gelatiniform plaques; (b) the ulcerovegeta- tive form; (c) suppurative form. Concerning group (a) with gelatiniform plaques, it is difficult to consider this as other than an early manifestation of the intimal proliferation of arterial sclerosis and not a true inflammatory process. (6) The vegetative form may occur alone or with valvular vegetations. Its usual seat is in the first part of the ascending aorta, and it may be the source of embolus or the seat of a rupture of the vessel. (c) Suppurative aortitis is practically always associated with ulcerative endocarditis; the inflam- mation commences between the outer and middle coat and may extend like a dissecting aneurysm or may rupture into the lumen of the vessel. Aortitis, acute or subacute, is always of infectious origin and though it may occur in the previously healthy vessel it more readily attacks one already atheromatous. Etiology. — It may occur by extension from tumors or abscess of the mediastinum or from tracheal ulceration or in the course of the infectious fevers. Typhoid fever, chiefly during the third week, may initiate it, and in syphilis in the secondary stage an acute form may arise. The symptoms of aortitis are vague, though an elab- orate symptomatology has been formulated by some. Dj'sphagia from pressure of the food bolus, epigas- tric pain, and vomiting have been described and J. Tessier mentions crises of pain in the abdomen and diarrhea in inflammation of the abdominal aorta. Fever is absent. Though the symptoms may be obscure or even absent there are some which are rather characteristic. Dyspnea is most important. It may be of the ordinary type or be severe and paroxysmal even in the absence of effort. Inspiration is prolonged, painful, and difficult, expiration is free and short. It resembles respiratory obstruction without its signs and has been attributed to bronchial spasm from reflex vagus irritation. Such intensity of symptoms in the absence of physical signs is diag- nostically important. Cough when it occurs is dry and sometimes strident. Pain. — At first this is a sensation of substernal constriction which later may appear as a burning or tearing at the base of the neck spreading to both shoulders and down the back. The ]iain is anginal in character but persists between the paroxysms and may appear during rest as (veil as on exertion. The physical signs consist in the aortic pallor with usually a quick and often dicrotic pulse and in cases of some standing the signs of dilatation of the aorta described below. Prognosis. — The outlook in aortitis is not good. After from two to six months of symptoms, as a rule death ensues. The fatal ending may result from an anginal attack or acute edema of the lungs or more slowly from progressive cardiac failure. Recovery may take place chiefly in the typhoidal form. Other cases may drift into a condition of chronic aortitis. Diagnosis. — From its constant association with other diseases the recognition of an acute aortitis is no easy matter, its sign^ and symptoms being usually attributed to the coincident malady. In the words of Barie whose description of the condition I have largely followed — "IV aortite aigue demande a etre cherchee.'" With dyspnea and pain of the character mentioned, in association with a bounding and dicrotic pulse and the signs of aortic dilatation, increase of aortic dulness and elevation of the subclavian artery, the diagnosis is fairly well assured. Treatment, aside from that of the primary disease, is symptomatic — morphine and belladonna for pain, ire or dry cupping to the sternal region, amyl nitrite for the anginal attacks, and when the acute attack has passed, iodides given over long periods. Chronic Retrogressive Conditions.- — Though some of these are primarily inflammatory and may be spoken of as chronic aortitis, the majority are degenerative rather, and by the seat and the type of the degeneration are to be classified. The investigations of recent years by Jares, Klotz, and others have done much to classify this group of diseases. They found that the injection of such drugs as adrenalin, barium chloride, and digitalin, as well as diphtheria toxin into rabbits resulted in destruction of the muscle cells of the media which later under- went calcification, while injection of cultures of B. typhi and streptococci of low virulence gave rise to proliferative intimal changes without degeneration of the media. Klotz points out the similarity between the first or adrenalin type with the common or Monckberg type of nodular arteriosclerosis in man, The second or "infective" group is represented in man by a true inflammatory endarteritis. So far then as the aorta is concerned, the following groups may be recognized: 1. Chronic Aortitis. — An inflammatory endarteritis following typhoid fever and other infections. 2. Syphilitic Aortitis. — This is primarily a peri- arteritis and mesarteritis, the destructive changes being found in the muscular and elastic tissue with infiltration about the vasa vasorum running in from the adventitia, Thickening of the intima follows as a reactive change, but when the process is acute, aneurysm results. The site of election of this type is at the root of the vessel, in the lower part of the thoracic and lower part of the abdominal aorta. The patches may be of small size and separated. Irregularly radiating grooves or puckerings are seen on the intimal surface. Such a condition has also been reported by Klotz in an infant with congenital syphilis. 3. Atheroma. — Intimal proliferation, non-inflam- matory. Following weakening of the media _ there develops a proliferation of the cells of the intima and subendothelial connective tissue. These patches occur in order of frequency in the ascending aorta, anh, thoracic and abdominal portions. In time they undergo hyaline and fatty degenera- tion and calcareous deposition forming atheromatous plaques which are most marked over the curves, 1« in lings, and divisions into branches of the vessel. The aorta may be markedly atheromatous with 494 REFERENCE IIWHH00K OF THE MEDICAL SCIENCES Aphasia but little sign of thickening of the peripheral arteries and via vi a. I. Medial Degeneration. — 11ns, the Monckberg type, has been mentioned above as analogous to lie "adrenalin" type of experimental arteriosclerosis. [n the aorta it is this type which is chiefly associated with thinning of the walls and diffuse dilatation and in the peripheral vessels with the nodular form of gdero i I, EClotz makes mention of a group of eases in which the aorta is macroscopically healthy but in ch microscopical examination shows a marked deposit of calcium in the degenerated muscle cells of the middle layer of the media. The outer layer nourished from tin' vasa vasorum ami the inner from the blood stream being little affected. This form was found in patients in the latter half of life. \tion or thi: Aorta. — This condition is in which tln> vessel, instead of giving away at one point with the gradual development of an aneurysmal tun, or. becomes uniformly enlarged and this enlarge- ment may be present in the first part only or may Oi i upy the whole vessel as far as the opening in the diaphragm. As distinguished from aneurysm again, dilatation of the aorta is not a sequence of syphilis which causes calized weakening of the aorta, but rather of an acute aortitis or of tin/ Monckberg type of arterio- sclerosis, in both of which the aortic weakening is, uniform and diffuse. [t is commoner in males than in females in the proportion of 9 to 1. I'd, iw the age of thirty and over that of sixty years it is relatively rare, the three intervening decades con- tributing most of the cases in equal numbers. Alcohol, tobacco, and hard work, especially periodical exertion, are figures in the etiology, but as mentioned above syphilis appears in the minority of as against the majority in aneurysm. Causation. — Granted a diffuse weakening of the aortic wall, the impact of the blood column causes not only a widening but a lengthening of the artery and as it is fixed at the heart end, it N pushed sidewise and upward as well as having its caliber increased and its walls thinned. Symptoms are sometimes absent but usually the two complaints are made of dyspnea and pain under the sternum. The pain may be referred to one or the other shoulder or the root of the neck. The physical signs correspond with the anatomical condition. They are (a) visible pulsation in the ud space with some lifting of the manubrium. McCrae points out the contrast between the marked visible and the slight palpable lift of the sternum. (b) Increased dulness over the sternum. The following figures are given of the dulness in the second space transversely. Average Mliii 5 cm. Woman 3 cm. If the figures are greater than these, dilatation is suggested. A^ a matter of fact measurements of 7 to 10 cm. or more are found in dilatation. The dulness is Usually greater to the left than to the right. (c) Elevation of the subclavian artery so that its pulsation is felt above the sternal notch and above the inner end of the clavicle. The aortic second sound has usually not only the high pitch of increased tension but a clinking amphoric character, and this may be made out by auscultation in the suprasternal notch more readily than in the second interspace. Contrary to what might be expected, the blood pressure is raised little, if any, above the normal. (e) The fluoroscope shows a shadow to the left and sometimes to the right of the usual aortic area. laximum Minimum 5.5 cm. 4 cm. 3.5 cm. 2.5 cm. Diagnosis. — from trui oi the pp ence of the above sign-, the absence of localized pre signs and of expansile pul ation, and the r-ray picture b ill usually m:ii e the destine! ton. Hodgson's D ■••■ i thi name given to dilatation of the aorta which involves the aortic ring, cat coincident aortic insufficiency. Thrombosis of the Aorta. — 'this is rare. It oeriiis in atheromatous arteries nearly always in the abdominal aorta a short distance above the bifurca- tion. In Barth's case it extended up to the renal arteries. The thrombus is stratified, with a soft center, the periphery showing primary clotting at the intiina. If the thrombosis is complete ii results in severe jiaiu, paraplegia, later gangrene and death. If incomplete, p;iin and 1 1 1 1 111 1 mess in the legs ap- pear, followed by weakness amounting to paresis. In one case the patient is reported to have lived two years when paraplegia became complete. Embolism results from endocarditis, simple or malignant, or from atheroma. The onset is sudden with severe abdominal or leg pains, sometimes with rigidity or convulsive move- ments. The legs become cold and blue and gangrene later develops. Rupture of the Aorta. — This is usually an accident of later life and with but few exceptions oceius in vessels previously diseased. Acute aortitis, atheroma, and tuberculosis have been found, while invasion of the aorta by cancer of the esophagus has also occurred. The rupture is usually intrapericardial and the tear is usually single, but occasionally multiple. The rupture is nearly always in two stages, through the intima first, with the formation of a dissecting aneurysm and from minutes to days later and at another level through the other coats. The symptoms are sudden, severe, thoracic pain with syncope and death. The rupture may occur into any of the neighbor- ing organs. A. H. Gordon. Aphasia. — See Speech, Disorders of. Aphonia signifies loss of the voice. It may result from disease or injury of the vocal apparatus, particu- larly the larynx, maybe a congenital affair (see Deaf- mutism), may result from paralysis of one or more of the laryngeal muscles, or be purely ideogenic in origin, forming a constituent part of a neurosis, psychoneurosis, or psychosis, as, for instance, in anxiety neuroses, hysteria, compulsion neuroses, or dementia pra?cox respectively. Only the neurological types of aphonia are discussed here. These result. from paralysis of the laryngeal muscles, either from definite pressure or from inflammation of the motor nerves or from psychic causes. The superior laryn- geal nerve sends motor filaments to the cricothyroid muscle only, the recurrent laryngeal supplies the greater motor innervation to the larynx, and disease of this nerve is responsible for most of the aphonias, partial or complete. Complete aphonia usually results from bilateral lesions; unilateral recurrens palsy may cause an initial aphonia, but later the voice can be used, although it is much modified. Central laryngeal paNies resulting in aphonia are most frequent in tabes. Aphonia is often then associated with Iaryngea, crises, excessive coughing, huskiness, loss of voicel and pain. A few rare instances are due to syringo- myelia. Rethi, in his monograph on laryngeal symptoms in multiple sclerosis, has collected a comparatively large number of palsies in this disease. Other syphilitic disorders than tabes may account for recurrent laryngeal palsies. Among the rarer 495 Aphasia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES causes are various growths of the neck and mediasti- num pressing on the nerve — carcinoma, enlarged lymph nodes in the posterior mediastinum, foreign bodies, aneurysm, esophageal growths. Occasionally overuse may cause fatigue palsy. Acute toxemias, diphtheria, measles, typhoid fever, lead, alcohol, copper, antimony, arsenic, etc., may occasionally be the etiological factor. Hysterical aphonias vary considerably. Here the mechanism causing the conversion may be very .superficial, in which case almost any hocus pocus, from a faradic spark to making a few hypnotic passes may. for a time at least, efface the symptom. Many of "these aphonias have owed their origin to acute psychical shock: they do not represent the conversion of long suppressed complexes. Many of the so-called cures, however, prove to be fallacious. In dispensary as well as in private practice such patients go the rounds. Those patients, whose aphonia represents a definite psychic conversion, either as a defense or a retention mechanism, are rarely cured by the superficial psychotherapy of suggestion, no matter what its particular form may be. Such patients are usually cured only by a complete psychoanalysis. Smith Ely Jelliffe. Aphrodisiacs. — These are agents, medicinal, physical, psychic, or hygienic, which increase sexual desire or ability. Some act by increasing desire, others by increasing or restoring the ability to perform the sexual act. Loss of sexual power may have origin in various ■ways and is frequently divided into organic, psychic, irritable, and paralytic. A distinction is also to be made between anaphrodisia, or absence of desire, and impotence, or inability to perform the sexual act. Organic impotence is dependent upon structural change, either congenital or acquired, such as anoma- lies, malformations, new growths, etc., for which relief must be sought by surgical or other special treatment. For nervous or irritable impotence, which is due generally to weakness of the genital organs and ab- normal excitement of the reflex centers causing pre- irature ejaculations, or due to irritations caused by some morbid condition of the urine or by the presence ot strictures, recourse must be had to measures such as the passage of a cold sound and other local treat- ment, which will relieve the causative factor. In paralytic impotence, caused by disease of the central nervous system, syphilis, anemia, systemic poisoning from lead, tobacco, etc., the indication is to remove the cause, when possible, to build up the patient by general tonic treatment, and to restore sexual tone by electricity, mix vomica, and other aphrodis- iac drugs. Psychical loss of sexual power is best treated by suggestion combined with the exhibition of strychnine or mix vomica. Most cases are due to nervousness, overwrought desire, indifference, grief, fright, and mental preoccupation. If the case has its origin in nervousness caused by fear of the consequences of early abuse, psychotherapy is the most effective measure. Tin' patient must be told to abstain from any attempt at sexual intercourse for one or two weeks and at the same time be given strychnine in small doses or cannabis indica. Those cases depending upon overwrought desire, frequently seen in newly married men after long engagements or sexual abstinence, are best treated by tin- temporary use of the bromides, together with suggestion. For these and for the remaining class of cases indications will be found for prescribing such general measures as hydrotherapy with massage, tonics, such as mix vomica, a diet consisting of highly seasoned food, red meats, and freedom from exhausting mental or physical work. Among the aphrodisiac drugs, mix 496 vomica (strychnine) and phosphorus enjoy the most repute. Ergot is said to be of value in those case-, of impotence which depend upon lack of erectile power and among drugs of use in pure anaphrodisia as distinguished from impotence, damiana, caffeine, and cannabis indica are recommended. Alcohol in small il(i1 ii 'resins cause irritation of the urinary tract and may indirectly stimulate the sexual appetite, but their use is to be condemmed as unscientific and dangerous. Other agents used are alternate applications of hot and cold water locally, electricity applied to the urethra or to the rectum, and the passage of a sound reinforced either by electric stimulation or by cold. In general more can be accomplished by hygienic and moral measures, tonics, rest, long hours of sleep, and the avoidance of worry than by the use of any of the so-called aphrodisiac drugs. Charles Adams Holder. Aphthae. — See Mouth, Diseases of the. Aphthae Tropica. — See Sprue. Aplasia. — See Agenesia. Apnea. — See Asphyxia. Apocodeine. — A grayish-yellow amorphous powder, C ls H 19 N0 7 , soluble in water and alcohol. It bears the same relation to codeine as apomorphine does to morphine. The hydrochloride which is readily soluble in water is the salt employed. Physiologically it has the remarkable property of depressing or paralyzing the sympathetic nerve-endings, and for this has come into extensive use in experimental work. It is directly antagonistic to adrenalin. Therapeutically its only use is as a purgative that can be administered hypodermatically, its action being to cut off the splanchnic impulses which are the normal inhibitory stimuli of the bowel. It has not proven to be of very great value, and its use is not without the danger of arterial relaxation with fall in blood-pressure. The hypodermic dose for cathartic purposes is half a grain (0.03). W. A. Bastedo. Apocynacese. — (The Dogbane, Oleander or Stro- phanthus family.) A great family of 130 genera and more than 1,000 species, very abundant in the tropics of both hemispheres, a few extending into the temperate zones. The plants are almost all trees or erect or climbing shrubs, with milky juice, and are highly ornamental and frequently cultivated for decorative purposes. The juices of Landolphia, Hancornia, and some others are utilized in the production of rubber. Valuable timbers are yielded by several species. The most noteworthy characteristic of the family is its poisonous nature, few other families being able to compare with it in this respect. Many of the species have been utilized as arrow poisons, and a number of these have been in- troduced into the materia medica. The active consti- tuents are mostly glucosidal, uncommonly alkaloiihil. The action is chiefly upon the heart, stimulant in small doses, ultimately paralyzant, and thus fre- quently powerfully diuretic. Often, also, they are irritant emetico-cathartics. Their action is so powerful that even minute differences between them are of importance, and new remedies introduced from this family are always worthy of careful atten- tion. The important medicinal genera are strophan- tus, aspidosperma, apocynum, and alstonia. The poisonous principles are widely distributed through the plant bodies. H. H. Rusby. REFERENCE HAXDROOK OF THE MEDICAL SCIENCES Ippendlcostom; Apocynum. — Canadian Hemp, Dogbane. The root of Apocynum cannabinum L. (Fam. Apocynaceai) l . S. P. Up to a comparatively recent period the fenus Ipoeynum was supposed to contain, in the Astern United States, bul two species, A. canna- binum L. and A. andro&amifolium L. As the latter was known to have but a weak physiological action, it was supposed to 1"' necessary to exclude only this well-known species from the drug in order to insure it- full properties. It is now known that the several supposed varieties of A. cannabinum are perfectly distinct species. A. cannabinum, then-fun', as it has been understood and collected, is in reality several ibably four, at least) distinct species. That some one Or more Of these species is a powerful and im- int medicine is indubitable, in view of the evi- dence presented; hut in view of the aumerous recorded failures, it is equally certain that not all of them are SO. Wo are at present quite ignorant as to which is the ac- tive species, all statements of manufacturers, as well as tlie Pharmacopoeia, to the contrary notwithstanding. The entire comparative study of these species is still before us. Under these circumstances any specific pharmacological account of the drug is out of the question. The plants are erect, perennial herbs, growing by preference along railroads and roadsides. They propagate by long, horizontal underground struc- tures, which appear to combine the characters of both root and rhizome. The latter is the part used. The aerial portion may be smooth or pubescent, and is usually purple or purplish. The leaves are oppo- site, oblong, or oval-ovate, thickish, mucronate. The stem is branched above and bears very small white or greenish-white flowers in close cymes. The fruit is a pair of long slender follicles, filled with small plumose seeds. The entire plant exudes an abundant milky juice. The drug occurs in long, rather straight pieces, of about the thickness of a lead pencil and sparingly branched. It is of a brown color, having an orange shade if not old and stale. The very thick bark exhibits few coarse wrinkles, finer nerves, and coarse circular fissures, and is pinkish-white internally. The wood is yellowish, very soft and brittle, its pores large enough to be visible to the naked eye. It contains resin, tannin, starch, an amaroid, and the peculiar crystalline body apocynin, soluble in alcohol, and the glucoside apocynein, soluble in water and of feeble action. The chief activity is believed to reside in the crystalline bitter principle cynotoxin, which occurs in white rhombic pyramids, insoluble in water and melting and decomposing at 165° C. Quinemore assigns to it the formula C\, H 2S O . Apocynum is a cardiac stimulant and a diuretic, as well as a nauseat- ing expectorant. The most important use of the drug is in causing the removal of dropsical effusions. Y fluid extract is official, the dose of which is irt; v. to xxx.(0.o to.'.O). H. H. Rusbt. Apomorphine fC,,H n NO,). — Apomorphine is an alkaloid derived from morphine by abstracting from the latter a molecule of water. This is done by heating it in sealed tubes with zinc chloride or hydro- chloric acid. It may also be derived from codeine. Jt is commonly used in the form of the hydrochlorate, which is official. The Pharmacopoeia describes it as in minute, grayish-white shining, acicular crystal-, without odor, having a faintly bitter taste, and acquiring a greenish tint upon exposure to light and air. Soluble in 39.5 parts of water, or in sixteen parts at Su° C, in 38.2 parts of alcohol, or in thirty parts at f.o° C: verv little soluble in ether or chloro- form. When heated to near 100° C. (212° F.), the salt is decomposed, rapidly if in solution, slowly when dry. The properties of apomorphine are totally distinct from those of morphine. It is primarily an emetic, Vol. I.— 32 acting altogether centrally, and with great prompt- ness and power. It is secondarily an expectorant, increasing and greatly thinning the bronchial mucus. In poisoning, there is intoxication or delirium and paralysis of the motor nerves, with failure of respira- tion and especially of t he heart . In use, apomorphine i- probably our most prompt and energetic emetic, it special value being the promptness and certainty with which vomiting can be induced by hypodermic injection when, for any reason, the stomach cannot be acted upon to produce it. As an expectorant, it is perhaps our most useful agent for relieving a "dry ''cough. [f given early, it will do much to avert bronchitis, and it is also e eially useful in the hacking cough of tuberculosis. In infants, or in the aged, it is possible for large doses to suffocate by the excessive transudation into the bronchioles. The emetic dose for an adult is gr. ,'„ to J (0.006 to O.01); as an expectorant, gr. f to ..'„ (0.0015 to 0.003). II. II. Rusbt. Aponomma. — A genus of parasitic ticks usually found on reptiles. The body is ornate as a rule, and broad-oval in shape. See Arachnida. A.S.P. i Apoplexy. — See Cerebral Hemorrhage. Apoplexy, Spinal. — See Spinal Hemorrhage. Appendicitis. — See Cecum and Appendix, Diseases of the. Appendicostomy. — The operation termed "appendi- costomy" is done with the purpose of utilizing the appendix as a means of irrigation as well as for the introduction of medicaments through its lumen into the large intestine. The operation was named appendicostomy, according to our usual rules of nomenclature, by the present writer. History. — The operation was conceived and first carried out in 1902 by Dr. Robert F. Weir of New York City. He was to operate on a greatly reduced man thirty-one years of age, who had been suffering for three years from frequent bloody, thin stools, due to obstinate colitis. Dr. Weir entered the abdomen with the intention of doing a cecostomy, according to the Kader-Gibson method; however, "as the cecum was exposed, the appendix rose so suggestively into view" that he "determined to employ it to make a fistula." It was accordingly fastened to the skin and the rest of the wound closed; soon after it was used for irrigating the large bowel. The final result proved very satisfactory. Indications. — As stated above, the operation was originally designed for the surgical treatment of chronic colitis and sigmoiditis after internal medica- tion and high irrigation had proved ineffectual (Weir, Willy Meyer, Tut tie). Within a few years it was tested with success in all subdivisions of this trouble, i.e. the mucous, membranous, ulcerative, dysenteric, tuberculous, syphilitic, and amebic types. It has steadily grown in favor with surgeons all over the world and its indications have been gradually widened. It was but natural that soon its application was extended also to chronic intractable constipation. • Splendid results were seen. It was further found useful in the following diseases and conditions: Acute appendicitis (stump not to be tied, amputated, and inverted, but stitched into the abdominal wall for saline infusion in place of rectoclysis) ; acute septic general peritonitis with meteorism; in the treatment of enteric ulceration in cases of typhoid fever; for the more effectual introduction of nourishment, as a substitute for rectal feeding; to prevent recurrence in cases of intussusception of the ileocecal variety; as 497 Apdenplcostomy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES appendico-enterostomy in order to reach for irrigation also the lower end of the ileum. (See below.) Technique. — Examination of the appendix in a hundred autopsies selected at random, showed that appendicostomy could have been done in ninety-six per cent. The operation (as carried out by the writer) can be done under general, regional, or local an- esthesia. McBurney's intermuscular abdominal in- cision is used; the cecum is pulled forward, or, in the presence of adhesions, loosened, so that the base of the appendix corresponds to the level of the parietal peritoneum. Careful palpation of the appendix is made to determine the presence or absence of foreign bodies or fecal concretions. If any are present, an attempt is made to press them gently into the cecum or tip of the appendix; if this be impossible, careful tamponade, incision, removal of the body, and suture of the opening are called for. The further steps of the operations are: ligation of the distal half of the mesenteriolum; continuous catgut suture of the peritoneal wound, allowing the appendix to emerge at about its middle, one to two stitches to catch the caput coli near the base of the appendix (care must be taken not to injure or constrict the blood-vessels of the mesenteriolum) ; layer suture of the abdominal wall; one stitch to fix the mesenteriolum; (care must be taken that fascia does not strangulate the appendix); one subcuticular suture to penetrate the appendicular wall superficially, for proper outside anchoring; layer of sterile gauze dressing on sutured skin wound, divided to surround the appendix; gauze mops on top near base of organ; amputation about one-third to one-fourth inch above the level of the skin, secretion caught on mops, latter exchanged; introduction of small flexible bougie to ascertain the permeability of the appendicular lumen; (slight strictures can be immediately stretched, in which event a small Nelaton catheter remains in place) ; if no strictures are found removal of bougie; gentle bow-knot closure of the stump with catgut; final dressing; removal of the bow-knot after twenty-four hours; beginning irrigations. Varieties of Technique. — 1. Sharp muscular and peritoneal division in the same direction as the skin and fascia, exit of the base of the appendix at the lower angle of the peritoneal wound, the organ being then run up to the upper angle of the skin wound — or reversed, the base of the appendix emerging at the upper angle of the peritoneal wound, the organ being run obliquely downward through the abdominal parietes. The oblique course of the appendix can also be arranged for, when using the inter- muscular incision; the organ would then run sub- fascially above the muscles for some distance. Neither modification is recommended, as the re- quired frequent introduction of catheters or rubber tubes may cause traumatic irritation or even ulcera- ton at the kink (base of the appendix). The straight outward way appears to be the best. 2. Total ligation of the mesenteriolum. This is not advisable as a rule, since it may cause necrosis, especi- ally in diabetics. It may be indicated in cases of acute appendicitis in order to produce gangrene and more rapid closure of the hole in the cecal wall later on. However, this appears unsafe; complications may occur in the healing of the wound in the abdominal .wall. It is undoubtedly best to preserve the mesen- teriolum either entire or at least up to the place where amputation is comtemplated. This can be well determined by putting the appendix on the stretch when closing tin- wound. 3. Suture of the appendix in place, without fastening the caput coli to the parietal peritoneum. This is dangerous, as the intraabdominal part of the appendix would present a band that might, cause intestinal obstruction. The intraabdominal portion might also become perforated if the use of stiff bougies or catheters (silver) became necessary in order to pass the narrow lumen of the appendix. One such case has been observed in which perforation resulted, followed by general peritonitis and death. 4. Amputation of the appendix twenty-four to forty-eight hours after operation. This certainly guards best against possible infection. However, if the lumen be found absolutely impermeable, cecostomy would become necessary at a second operation; whereas, if it were so found at the comple- tion of the appendicostomy, the sutured abdominal wound could be quickly opened and cecostomy added at once. This is an important point. With ordinary precaution, soiling of the freshly sutured wound can be well prevented. It is self-understood that, if the appendix as such appears large, and its walls show no infiltration suggestive of strictures, it will always be safer for the patient if the amputa- tion be performed twenty-four hours later. 5. Appendico-enterostomy (Pringle). Anastomo- sis of the tip of the appendix with the lower end of the ileum. The appendix is fastened in the abdom- inal wound in such a manner that its middle projects; it is fixed to the abdominal wall; after forty-eight hours, an incision is made and a catheter is introduced to either side, thus reaching the large intestine as well as the ileum above the ileocecal valve. Choice between Appendicostomy and Cecos- tomy. — Appendicostomy appears to be the operation of choice in all cases in which the appendix is per- meable. It is simple, safe, and effective, and is also better as regards the after treatment. It does not necessitate the continuous wearing of a rubber tube within the canal. Possible Late Complications. — Aside from the one case of perforation of the intraabdominal portion of the appendix mentioned above, prolapse of the cecum through a large appendicular stump has once been observed by the writer. (Amebic dysentery; appendix led out straight; gradual prolapse; cured by operation. See Annals of Surgery, 1908, vol. xlvii., p. 808.) In one case the catheter left in place slipped into the gut and was later passed per rectum (Dawson). The catheter or drainage tube should always be secured with a safety pin outside, better still, be introduced for each irrigation and removed again after this procedure. After Treatment. — There is usually no leakage; a small dry gauze or ointment dressing is all that is required. If there should be some slight leakage from the stump of a large-sized appendix, a gently pressing truss with rubber pad, filled with water or glycerin, might be worn on top of the piece of gauze covering the opening during the time of utilization of the appendicostomy. Once or twice a day a rubber catheter or small rubber tube is introduced through the appendicular stump into the cecum, and the colon is flushed. Quinine solution 1:1500 alternating with nitrate of silver 1:2000, or a solution of sodium bicarbonate two per cent, and one of thymol 1:1000, alternating ice cold or hot, according to subjective prefer may be used for amebic dysentery; bichloride solution 1:2000, or thymol 1:1000, with antispecific general regime for chronic syphilitic ulcerative colitis; saline solution for cleansing, to be followed by pure balsam of Peru and iodoform emulsion injections in tubercu- lous ulcerative colitis, giving creosote or guaiacol internally, with a carefully selected diet, and, of course, the observance in addition of a general hvuienic regime; weak solution of epsom salts and cascara, etc. in small doses, even plain warm water, in cases of chronic constipation. Two quarts of fluid introduced through a tube Nos. 12 to 14 (French scale), can be made to pass the ■His REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ !•■•■- 1 i I .- entire large intestine within ten or fifteen minutes. During this time l lie patient had best lie on a Kelly Eits apron hanging into a pail, or on an ordinary ed-pan. Patients easily learn to flush the colon themselves; they certainly are not in need of hospital treatment during this period. In view of the obstinacy of chronic affections of the lame intestine and the tendency of the trouble to t. it is unwise to bring about definite closure of appendicular opening at too early a date. It represents a safetv valve in the true sense of the I. and may persist, just covered with a crust, oticed by the patient (writer's observation). If t!i g is to be kept patent and more secre- tion than usually seen is present, the serous cover of the projecting portion of the appendix above the skin may be removed and the remaining portion inverted into the lumen of the proximal portion. If, after a time, reopening of the appendicular lumen be desired, this is a simple matter, inasmuch as only the most distal (intracutaneous) part contracts; the rest of tlie canal remains patent ( Keatley). Definite Closure of the Appendicular Opening. — erization with nitrate of silver stick, or some kind of acid, better still, with a pointed Paquelin cautery, will be found effective. Results. — The mortality of the operation is practically nil. The few deaths that have been reported were not due to the operation as such. Immediate as well as late results have been very gratifying, especially in cases of amebic dysentery and .he various forms of chronic ulcerative colitis, that had baffled internal medication and irrigation and colonic flushing from below. The great majority of patients were cured, gaining many pounds in a short time. It has also been very gratifying to see cases of chronic syphilitic ulcerative affections of the colon, but particularly those of tuberculous character yield to irrigation and medication through the appendic- ular stump in a way that one might rightly call the patients cured (Pringle, Willy Meyer). There can be no doubt that the operation of appen- dieostomy represents a most effective addition to our surgical means of treating diseases of the large intestine. Affections that proved extremely obstin- ate, if not incurable by former methods, have been Been to yield nicely to the treatment made possible by appendicostomy. The operation has also proved useful in a number of other intraabdominal troubles and as an operative preventive against recurrence in cases of intussusception of the ileocecal variety. Willy Meyer. Appetite. — While frequently used to include sexual desire, the craving for various narcotics and stimu- lants, and while it might appropriately include the appreciation of a need for water, oxygen, etc., the term appetite is commonly limited to the desire to ingest more or less solid and nutritious material. Hunger indicates an actual deficiency of nutriment, with or without the realization of such deficiency. Appetite implies a mild degree of hunger, but em- phasizes the subjective sensation and implies, also, a greater or lesser anticipation or realization of gustatory pleasures. The more closely we approch natural con- ditions, the more nearly synonymous do appetite and hunger become; that is to say, appetite consists more of an actual desire for food, without much re- gard to its taste and flavor, while the more artificial the conditions and the less genuine hunger exists, the more appetite involves social, esthetic, and gustatory pleasures. But, even in a state of nature, most ani- mals exhibit certain preferences for food, not en- tirely explicable on metabolic grounds, and are liable to overeat if opportunity presents itself. However, in general, the rat me of appetite indicated by the herbivorous, graminivorous, carnivorous, omnivi u corresponds quite clo ely to the digestive and metab- olic capacities of the organism Vn artificial appetite i nut, as is sometimes imagined, confined to human beings, but is displayed by many lower animals in captivity or actually domesticated. Cattle are said to be fed to some extent on salt fish in arctic region cats, dogs, and horses usually develop a taste for sugar, and in the la-t feu years it ha- become quite common for eats kept in drug stores to eat ice , i ea Da, while dogs not belonging on the premises often hang about soda fountains on the chance of having this appetite gratified. < hie of the strangest appetites among the lower animals that has come to the at ten- don of the writer was instanced by a cat for musk melons. Appetite is commonly regarded as a pneumogastric reflex and properly, in so far as it is appeased by the distention of the rugs with even innutritious material and brought into play by the emptiness of the stom- ach. Except in this transitory sense, appetite cor- responds fairly well, both quantitatively and qualita- tively, to the actual needs of the body, for caloric energy, protein, carbohydrate, salines, antiscorbutics, etc. No adequate explanation of this can be offered. In diabetics, the use of saccharin temporarily cloys the appetite for sweets but does not satisfy the ultimate desire for carbohydrates. In certain in- dividuals, the carbohydrate appetite is mainly for sugars, in others for starches, but free indulgence in cither satisfies the appetite for both, though not necessarily changing the general personal appetite; which indeed is usually persistent. There is also a qualitative appetite for protein, especially for meat protein which is not appeased by food in general, though obviously habit has much to do with such appetites and a mera preference for an excess of meat may be controlled by an abundance of other food. It is doubtful whether an appetite for iron, iodine, and various salines can be demonstrated, but there is a distinct appetite for salt, seen in both man and the lower animals; and, on account of the formation of HC1 from NaCl and the special need of HC1 in pro- teolysis, the craving for salt is especially marked in persons with relatively carnivorous tastes and ten- dencies to hyperchlorhydria. There is also a dis- tinct appetite for antiscorbutics. For instance, dur- ing the Civil War, a company of soldiers who had subsisted largely on hardtack and salt meat for some weeks and among whom cases of camp diarrhea and mild scurvy had developed, entered a field of half frozen and decayed cabbages. Some of the sick men were so ravenous for fresh vegetable food that, despite the protests of their comrades, they ate large quantities of cabbage — and were cured of their prostration, skin lesions, and diarrhea. The antiscorbutic appetite is sometimes depressed by overindulgence in candy, etc., or, more frequently, in alcoholics. The writer has had two marked cases of scurvy develop in persons with no other reason for deprivation and cured by diet of fruits. Occasionally, although the hunger is assuaged by meals and the appetite is small, there is a vague hankering after something which the patient cannot identify. Finally, usually quite accidentally, some particular viand is encountered which "hits the spot," satisfies the craving, and improves the appetite and the nutrition. There is considerable dispute as to the degree to which a natural appetite is protective against actually toxic or harmful substances. Barring actual adultera- tion or tainting of food, many persons can eat with impunity anything for which they have an appetite, however unwholesome it may seem, while, owing to some idiosyncrasy, even very slight amounts of theo- retically wholesome food which is distasteful will cause nausea, diarrhea, etc. The lower animals are often 499 Appetite REFERENCE HANDBOOK OF THE MEDICAL SCIENCES supposed to be protected by instinct against toxic and harmful foods. This is not, however, the case. It is also contended that a perfectly natural appetite corresponds quantitatively to the demands of the system, and that ingestion in excess of metabolic demands is an artificially acquired vice. Observa- tion, however, shows that, on the one hand, the average appetite of civilized persons is not much beyond the theoretical demand in calories, not far- ther beyond this limit, indeed, than a fair margin of safety requires. On the other hand, among both human savages and the lower animals, we find that periods of enforced abstinence alternate with periods of excessive ingestion. The relation of the appetite curve to fasting periods is another interesting problem. The herbivorous animals spend most of their time when awake in eat- ing. Carnivorous animals, including omnivorous and primitive man, eat at irregular intervals, but it is not far from the truth to say that they eat whenever and as much as they can. In a state of civilization, most individuals and races or social groups have established customs regarding the frequency and relative amounts of different meals. To some degree, these customs depend upon occupation, wealth, etc., but only approximately so. The change in meal hours, in the relative importance of different meals, etc., which has occurred in this country within the last one or two generations, is largely due to diminu- tion of physical exercise and the impossibility of reaching home in the middle of the day. The relation of appetite to physiological conserva- tion of nutriment is an interesting corollary. Not to mention the various problems in regard to storage and utilization of fats, it is commonly held that the body has extremely limited capacity for storage of protein and carbohydrate. Yet we are developing on a large scale an appetite for a very small breakfast, a moderate luncheon, and a hearty dinner, the last, representing at least half the caloric energy of the total ration, being taken at the close of one day's work and about fourteen hours before the next begins. With so marked a discrepancy between empiricism and theory, the whole question of conservation of protein and carbohydrate needs further study. Appetite is well known to depend upon a great variety of sensory impressions and mental concep- tions. Taste, smell, and to a scarcely less degree sight, may either stimulate or inhibit appetite. Sensations of temperature and touch have a similar action, according to rather arbitrary customs that certain foods shall be hot, others cold, and that homogeneity and softness are a desideratum in some, while in others, as crackers, bread, mousse, etc., the opposite qualities are desired. The sense of equi- librium has an important negative bearing on appe- tite, as illustrated in seasickness. Sound can scarcely be said to have any influence on appetite except in the general way that any agreeable or disagreeable sensation may act upon the mind. Excessively loud noises, however, if continued, may affect the appetite on account of the simultaneous vibrations of the semicircular canals. Any conception, however suggested, as directly through any of the special senses or indirectly through memory, may affect the appetite in either way. Thus there is a germ of truth in the old story of the man who tied his com- panion before taking poison but whose life was nevertheless saved by the latter's presence of mind in narrating a disgusting tale. Pawlow's investiga- tions have verified and extended what has long been known: That smell, taste, and sight of food produce appetite by stimulating digestive secretions which, on the contrary, are inhibited by fear, anger, and excitement. Disturbances op Appetite. — Anorexia, lack of appetite, though usually a symptom of disease, 500 locally digestive or general, is often conservative. Even when there is interference with the special senses of taste and smell, appetite commonly remains, indeed in a purer type than usual because these two special senses are eliminated. Occasionally, howe\ er. there is no true appetite and the individual eats merely on account of a feeling of weakness or as an intelligent act to furnish nutrition. Such cases seem to.be due mainly to stoicism and habitual repression of self-indulgence, but they are also found in mild cases of melancholia among which may perhaps be included nostalgia. Hi/pcrorexia or Bulimia. — As the limitation of appetite depends mainly on a reflex from the disten- tion of the gastric rugae, bulimia is not so much the cause as the result of dilatation of the stomach, without marked pyloric obstruction. It is also encountered in various conditions in which excito- reflex stimuli are obtunded; as in general paresis, various forms of insanity, often in old age. Some- times, the enormous appetite is merely an expression of a delusion of grandeur. Bulimia is popularly regarded as a symptom of tape-worm and ascribed to the demands of the parasite. This explanation is, of course, absurd, as even the development of the fetus, whose size and metabolism are very much greater, causes no marked bulimia. The more accepted explanation is that the craving is due to the toxic or mechanical irritation of the parasite but, in the writer's experience, it is very seldom that an explanation is required, as the bulimia does not exist except in a small minority of cases. It should not be forgotten that the diagnosis of bulimia, like that of gastric dilatation, requires a weighing of conditions and not merely a measurement of ingesta. An ox-appetite is normal for one doing ox work. The excessive mental and physical activity and actual building of tissues by growing boys, require an amount of food that the larger adult, repeating the same mental tasks instead of passing constantly to new ones, exercising gently, and merely making good the waste of fully formed tissues, is inclined to regard as excessive. In young adults, an excessive ingestion is often due not to a genuine appetite but to the notion that physical and mental strength can be increased by depositing nutriment as one would deposit money in a bank. Idle persons also eat as a means of diversion and it is probable that, in addition to mild pathological failures of digestion and absorp- tion, the physiological economy of utilization really relaxes so that more food is needed. It is said that under the Roman empire it was quite a common practice to prolong the pleasure of eating by thrusting the finger down the throat after the stomach had been filled, so as to allow a repetition of the process without delay. The writer has encountered one such ease, in an otherwise dainty and refined old maid. This patient is thin. Indeed, bulimia is very apt to be attended by poor nutrition and slight deposition of fat and, conversely, fat persons are usually light eaters. Perverted Appetites and Cravings. — It is extremely difficult to draw hard and fast lines between natural and artificial appetites and between the latter and perverted cravings. At one time or another, nearly every plant and animal has been used as a food, and the esthetic notions with regard to what substances are proper and what improper foods, are difficult to explain. Many persons would no more eat frogs' legs than snakes; or horse meat than dog or cat flesh. In the eighteenth century, tea leaves were eaten like greens. Until about the middle of the nineteenth, tomatoes were called love apples — the term persists in some sections — and were used only as table orna- ments. Urodipsia may be merely suggested by olives but has a close analogue in the use of kidney. Coprophagia, at first thought not merely a perversion but an insane perversion of appetite, is duplicated by REFERENCE HANDBOOK 0] THE MEDICAL SCIENCES A|ir;i \la (he routine and inevitable use of deer intestine with oontents by the Indians, as affording the only avail- ; ,i,;. anti scorbutic food in winter; also by the practice of serving with game the " trail" which is the intestine and usually infested with parasites. We may also pause to reflect thai the hulrs in Swiss cheese are §ue to the colon bacillus and that, in cheeses, high meal, sour milk delicacies, liqueurs of various kinds, etc., nearly every possible method of decomposition is duplicated in food stuffs. Pica, the eating of gravel, clay, plaster, magnesia, tale, slate, etc., is often seen in very small children, nt puberty, especially in girls, sometimes in pregnant v, , wnen. Among savages and sometimes among the poorer classes of civilized nations, clay eating is a re-ort in famine. The clay habil favors the entrance of the hook worm. When we consider the custom of Qg children, of putting all sorts of articles in the mouth, and the pleasure which many adults derive from "dry smoking," holding a tooth-pick, straw, etc., in the mouth, and the commercial importance of chewing, we must analyze each case carefully, to distinguish between a genuine perverted appetite and a men' habit. It is also worth while to remember that a good many vegetables consisting of leaves, stalks etc., are only slightly richer in nutriment than the mineral matters discussed under the head of pica. Peculiar and often highly individualized cravings are quite often encountered in pregnant women, sometimes in fever patients, often in invalids, espe- cially in the neurotic. It should not be forgotten that some such cravings, as for pickles, salt, etc., may possibly represent a genuine need of the body. At any rate, if the craving can be gratified with a flavor, without introducing any appreciable quantity of a deleterious substance, it is much better to gratify it. For instance, a few whiffs of a cigarette after an operation, or during typhoid fever, may cause greater subjective relief than three centigrams of morphine, the actual amount of toxic substances introduced being infinitcssimal. In other instances, the craving may be for something not deleterious at all except that it is not ordinarily given in the particular condi- tion and that it should not be given in any consider- able amount — for example, a very little sugar or soft fruit, weak coffee, chocolate, or the like, may be introduced into almost any dietary. A. L. Benedict. Apraxia. — This term was first used by Gogol in is;:; in a Breslau thesis on Aphasia. His patient ate his soap, urinated in his water pitcher, and was de- BCribed as having lost his understanding for objects. Such defects had been noted before, and it is worthy of note that Hughlings Jackson in 1866 called atten- tion to a similar type of phenomenon, and attached much importance to it. Quaglino in 1S67 described a case, Finkelnburg in 1S70 another, in which recog- nition of tilings and people was lost, and he created the term asymbolia. Wernicke in 1S74 expanded the term asymbolia, while Freud finally utilized the term agnosia to cover all types of loss of sensory or motor object images, apraxia then being arranged as a form of loss of knowledge of objects, really a form of visual agnosia. From this early use of the term apraxia there has been a distinct variation, brought prominently into the foreground by Liepmann in 1900. He defined the disturbance as a lack of knowledge of the use of objects, although there was no true agnosia or loss of recognition of what they were. Out of the later studies of Liepmann, Pick, von Monakow, D'Hollander and others has come the following general definition of apraxia: It consists in an inability to perform certain sub- jectively purposeful movements, or movement com- plexes, the motor power, sensation, and coordina- tion being intact. Such an inability will naturally depend upon at least three factors; one may be unable to recognize the object which is to be u ed, in which case we can speak of a sensmv apraxia. in the sense as one speaks of a sensory aphasia, or a visual agnosia. Should the patient recognize the object, call it perhaps by name, slate its use, and yet in attempting to use it totally fail in proper motor act, one speaks of a motor apraxia. It being under- stood here that, there is no necessary change in the motor tire, with either incoming sensory or outgoing motor side. Thus one can speak, as \\ ilsmi has done, of a motor aphasic as having an apraxia of his speech musculature. In grave intracerebral changes the knowledge of the proper kinetic images to carry out purposeful actions in the arms and legs may be com- plexly involved. Hen' one speaks of an intrapsychic •da. Clinically it is usually overlaid in the gen- eral psychic loss, often spoken of loosely as dementia. Apraxia may be then either sensory or motor; it may be unilateral or bilateral, it may be extensive, involving many muscular groups or may be limited to a few, such as an inability to protrude the tongue on demand with perfect power in other movements, or closure of the eyelids, etc. A certain patient with motor apraxia on being given a cigarette holder and cigarette recognized the objects, said they were for smoking, but on being told to put them together was unable to make the correct movements, and finally gave up. Another patient was given a candle and a match-box. She took out a match, made rubbing movements with it in the air above the candle, and then reinserted it in the box. In Liepmann's celebrated case the patient was able to do things with his left hand, but failed entirely with Iris right. When told to brush the examiner's coat, he picked up a corner of it carefully in his left hand, then picked up the brush in his right hand, with which he made movements as if to brush his hair. Asked to pour water into a glass from a carafe, he grasped the carafe with his left hand to pour water into the glass held in the right hand, after which the glass was brought to the mouth without any water in it. These patients fail to carry out the simple commands to blow a kiss, make a threatening fist, soldier's salute, etc. In ideomotor apraxia the situation is more compli- cated. One patient given a tooth brush recognized it, then began to brush his beard with it clumsily; another being given a pistol which he named cor- rectly, on being told to shoot it grasped the barrel, blinked and put the muzzle into his left eye. Another patient, being given a cigar and a match-box opened the latter, stuck the cigar in it, and tried to shut the box as though it were a cigar cutter. Then taking the cigar out rubbed it on the side of the box as though it were a match. The entire order of pro- cedure was badly devised. Like aphasia, apraxia is largely implicated in left hemisphere lesions. It is usually due to a supra- capsular lesion. In left hemisphere disease, the apraxia may be homo-or heterolateral, and in homolateral apraxias the corpus callosum is usually involved. In left frontal disease apraxia has been found especially with lesions of the first and second frontal convolu- tions. Anything that brings about an isolation, diaschisis of the left frontal area from the right, frontal area will seem to bring about an apraxia, or when there is any isolation of the left frontal from other parts of the cortex. Naturally a great diversity of pathological condi- tions may happen to bring such associations to pass. Thus an apraxia is to be looked for in tumors, paresis, multiple sclerosis, hemorrhages, etc. The subject of apraxia is well discussed bv Wilson, Brain, vol. xxxi., 1908, p. 164; by D'Hollander, Bull. 501 Apraxia REFERENCE HANDBOOK OF THE MEDICAL SCIENCES delaSoc.de med. mentale de Belgique, 1907; by Liep- mann, Drei Aufsatze, Berlin, 190S; Pick, Studien iiber motorische Apraxie, 1905; and Glascock, Journal of Nervous and Mental Disease, 1903. Smith Ely Jelliffe. Aquas. — Waters, or medicated waters, are clear, aqueous solutions of volatile substances; these latter may be solid, liquid, or gaseous. They are prepared in various ways: By simple solution in cold or hot water, by nitration through an absorbent powder, by percolation through cotton saturated with the substance, and by distillation. As a class the aquffi have but slight medicinal value, and deteriorate if kept for a long time. They are mainly used as vehicles and solvents. In the U. S. P. there are nineteen official waters: V. S. P. Latin Title. Aqua Aqua ammonue Aqua ammonia fortior. . - Aqua amygdalae amane... Aqua anisi Aqua aurantii florum Aqua aurantii florum fortior. Aqua camphora 1 Aqua chloroformi Aqua cinnamomi Aqua creosoti Aqua destillata Aqua fcrniculi Aqua hamamelidis Aqua hydrogenii dioxidi. . Aqua menthre piperita?. . . Aqua mentha? viridis Aqua rosse Aqua rosa? fortior Water. Ammonia water Stronger ammonia water. Bitter almond water Anise water. Orange flower water .Stronger orange flower water. Camphor water Chloroform water Cinnamon water Creosote water Distilled water. Fennel water Witch hazel water Solution of hydrogen di- oxide. Peppermint water Spearmint water Rose water Stronger rose water HJxv. 5i 5ss. 5«s. oij- 3>.i- 5ss. oss. 3u- 5ss. 5i.i. 5i. Sss. 3ss. 5ss. 3ij. R. J. E. Scott. Aquifoliaceae. — Ilicineoe (the Ilex or Holly family.) A family of three genera and some 200 species, chiefly of North and South America. It is chiefly notable for the presence of an appreciable amount of caffeine in the leaves of at least two species, on account of which they have been used as bever- ages (see Mate and Cassine). Other species have been used as bitter tonics and alteratives (see Alder, Black, and Holly). H. H. Rusby. Araceae. — Aroidere (the Arum family.) A largo family, of more than 100 genera, growing mostly in the tropics of both hemispheres. Many species, as the cultivated calla, are highly ornamental. Calocasia produces an important starch-yielding corm, and monstera, an edible fruit. Many of the tropical species are known as poisons, but their constituents and actions are little known. It is remarkable that a few northern species in the genera Spathyema, Acorus, Arum, and Ariswma, should represent about all the medicinal contributions of the family, and more active agents may be expected to be made known in it in future. H. H. Rusby. Arachnida. — In the branch or phylum Arthropoda, characterized by bilateral symmetry, by meta- meric segmentation of a heteronomous type, and by the possession of jointed appendages, typically a single p.'iir for each mctamere of the body, may be distinguished five great groups: the Crustacea, includ- ing crabs, lobsters, water fleas, etc.; the Onychophora including but a single genus, Peripatus; the Myria- poda, including millipeds, centipeds, etc.; the Insecta, including the true insects; and the Arachnidaor Arach- noidea. The latter may be defined as air-breathing arthropods, characterized by the fusion of head and thorax into a single region, the cephalothorax, which is without antennae, but bears two pairs of appendages more or less closely connected with the mouth, and four pairs of walking legs. The abdo- men, which may or may not be segmented, is usually distinct from the cephalothorax, though in the mites it is fused with it. The class Arachnida is subdivided by various au- thorities into from seven to nine orders, among which are the Scorpionida or true scorpions, the Pseudo- scorpionida or book-scorpions, the Phalangida or "Daddy Long-legs," the Araneida or true spiders, the Acarida or mites, and the Linguatulida. The true scorpions have the power to inflict a pain- ful wound by the sting located at the tip of the abdo- men. In the case of large tropical species the effect, of the sting may even cause the death of small children, but only in the most exceptional cases does it seriously affect an adult. There is injected at the time a quantity of poison from a gland in the last joint of the abdomen; its action is in general to irri- tate nerve centers while at the same time producing paralysis of motor nerves. The sting of the smaller species found in the United States is harmless, giving rise to a slight irritation, which lasts at most seven or eight days. Mr. Herbert H. Smith, the well-known col- lector in South and Central America and the West Indies, after enumerating symptoms and results in a number of carefully observed instances, says: "Prob- ably death might result in some cases, as (if reports are true) it does, rarely, from bee stings My wife was stung by a small one; the wound was exceed- ingly painful. By the advice of a servant, she held the finger for an hour in hot sweet oil, mixed with an equal measure of laudanum. There was no swelling and three hours after all pain had left her." In Africa scorpion sting is not regarded so lightly and the occurrence of gangrene as a result is on record while a brawny swelling and more or less collapse are the usual sequels for adults save in natives who seem to have developed some immunity. In children under twelve the sting produces an effect not unlike tetanus. An antiserum for scorpion venom has been prepared and used by Todd at Cairo and in upper Egypt. It appears to have a marked palliative effect on the intense pain following the sting, but in spite of its use some young children have not survived the effects of the scorpion poison. Among the spiders also there are those that are able to pierce the human skin by the action of the jaws or chclicerce which also contain the orifices of a pair of poison glands. The effect of a spider's bite on an adult has, however, been much exaggerated; of itself the bite produces at most a slight dermal swell- ing which soon disappears. The large hairy thera- phosids, popularly known as tarantulas, are not to be called dangerous. Their bite is painful, but the inflammation, though often violent, subsides rapidly. On the other hand, several cases on record of death from spider's bite have been traced to a small spider (Latrodectus viactans) which is related to supposedly poisonous species in other countries of the world, and it is not unlikely that the spiders of this genus secrete a more powerful fluid than others. The condition of the patient, his susceptibility to poison, and other important facts are not on record in these cases, and it may happen that the chance introduction of extra- neous matter through the bite has given rise to the more serious and rarely to the fatal results noted. There are no spiders in this country of which it may positively be affirmed that they are venomous, though certain South American species enjoy an evil reputa- tion which is undoubtedly well founded. 502 REFERENCE HANDBOOK OF THE MEDICAL Si'IKVKS Arachnlrla I.i\i;i!.\tulida. — The highly modified forma in- cluded in this group have a certain superficial resem- blance to tapeworms, From which, however, they differ radically in structure. Their closest affinities are doubtless to be found among the arachnids of which they arc here considered as an order. Accord- ing to Sambon their structure, their blood-sucking habit, and the pari they play in fostering the sporogonic cycle of the haunogregarines peculiar to their respective reptilian hosts, suggest relationship to the ectopara- site Ixodidse. The body (Fig. 260) is elongate, cylindrical or flattened; the anterior end (cephalothorax) is more or less clearly marked off from the rest (abdomen), which is subdivided by ambulations variable in number and distinctness. At the blunter, ante- rior end the mouth is located on the ventral surface and provided on either side with two protractile hooks, con- tained in sheaths or pockets. These hooks represent the mouth parts of other arachnids, while other append- ages are entirely lacking. There is no special respiratory apparatus, and the so-called stigmata are but the orifices of dermal glands. At the posterior end may be found the anal opening. The linguatules are of separate sexes, the males being much the smaller. The female genital pore is located near the anus, the male on the ventral surface near the anterior end of the abdomen. The adults live in the nasal cavities and lungs of mammals or reptiles, and the eggs, produced here in large numbers, must be imported by chance into a suitable guatula rhinaria, secondary host in which they give female. Natural rise to tetrapod, acariform embryos size. (After (Fig. 261, b) that metamorphose into Br»un.) a second stage (nymph, Fig. 261, c), manifesting the main features of the adult. By a migration usually semi-passive, this form reaches the primary host and attains full de- velopment in it. Linguatula Frohlich. — Body flattened, with arched dorsum and crenated margins. Body cavity extend- ing into the lateral regions of the rings (pectinate). Fig. 261. — Linguatula rhinaria, Stages of Development. ( After Leuckart.) a,_ Egg with embryo; 6, free embryo; c, nymph or pupa. Magnified." Linguatula rhinaria Pilger = Pentastoma tmnioides Rud. — Larva = P. denticulatum Rud. and P. ser- ratum Frohlich. — Body lanceolate, attenuated pos- teriad; head rounded, annuli circa 90, hooks acumi- nate, enlarged toward the base, with basal joint elongated proximad. Female S0-100 mm. long, 8-10 nun. broad anteriorly, 2 mm. posteriorly. Male 1 8-20 mm. long by '■'> mm. broad, decreasing to 0.5 mm. The adult inhabits the nasal cavities of many mammals, particularly the carnivora, among which the dog is perhaps most- commonly infested. The larva occurs in the viscera of the herbivorous mam- mals. The masses of eggs containing well-de- veloped embryos are deposited by the adult female n the nasal mucus and distributed over grass, etc., with which they are swallowed chiefly by rabbits, but even, as on salads, by man himself. Hatched in the stomach the larva; penetrate the intestinal wall and encyst in liver or mesentery, where after nine eedyses covering a period of from five to six months, they reach the second stage, characterized by the rows of retrorse spines on each an- nulus. From the liver they may, as some maintain, wander out actively and if eaten by a dog reach the nasal cavities di- rectly; or they may await the consumption of the flesh by some carnivorous form, in which case they are set free in the stomach and wander through the tissue to the lungand thence by the air passages to their final location. Some authorities deny the possibility of the larva deserting its cyst and wander- ing out, and maintain that the transmission is always passive. In man older cysts regularly become calcified. Rare instances of the occur- rence of the adult in man are on record, probably due to tin 1 consumption of poorly cooked flesh (mutton) containing the larva3. The larva (Fig. 262) has been reported frequently as a human parasite, chiefly from Germany and Austria. Most commonly found in the liver, it has also been met with in other viscera. Here it occurs in sharply defined yellow tumors, embedded in the sub- stance of the liver or protruding somewhat from its surface. The tough capsule contains caseous or cal- careous contents, and varies in diameter from about 1 cm. to the size of a pea. The capsules are less fre- quently found scattered irregularly over the surface of the peritoneum. The parasite is probably innocuous, as its presence has not been suspected previous to autopsies, at which Virchow reported the parasite in Wurzburg and Berlin and Wagner in Leipsig. Frerichs found it in Breslau five times in forty-seven autopsies, Zenker found it in Dresden nine times in 168 cases, Heschl at Vienna five times in twenty; Klebs at Basel, however only twice in 1,914 cases. Laengner recently records fifteen in 500 autopsies in Berlin; the larva? were found seven times in the liver, seven t imes in the intestinal wall and once in the mesentery. He believes this parasite is frequent and often over- looked. The adult occurs in seven per cent, of the dogs examined in Berlin. I have one record of its presence in man in this country, although it has been reported rarely from other hosts (rabbit and cattle). This case of infection with Linguatula serrata, the larval form of L. rhinaria, has been reported by Darling and Clark from the Canal Zone. At the autopsy of a Nicaraguan, a larval linguatulid was found crawling over the cut surface of the lung and along the pleura. It was the only specimen present and its exact location during the life of the host could not be determined in spite of careful search. This is the first instance on record cf the occurrence of this Fig. 262.— Lingua- tula denticulata, Larva of L. rhinaria. (After Leuckart.) Magnified. 503 Arachnida REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 263. — Nymphal Stage of Porocephalus arinillatus in the liver. (After Sambon.) parasite in a native of the American continent. Two cases have been observed at Ancon Hospital during the past six years. The other, a larva also, having been taken from the feces of a resident. _ The adult parasite has never been found in that territory. Porocephalus. — Body cylindrical; body cavity con- tinuous. Porocephalus arniillatus (Wyman) = Linguatula armillata Wyman. — Larva = L. diesingii van Ben.; Pentastomum constrictuin v. Siebold; Nematoideum hominis (viscerum) Diesing. Color in life lemon yellow; in preserved specimens ivory white. Elon- gate, vermiform; female 9 to 13 mm. long by 5 to 9 mm. broad, with eighteen to twenty-two rings in body; male 3 to 4.5 mm. long by 3 to 4 mm. broad, with sixteen to seventeen rings, cylindrical anteriorly, tapering poste- riorly, end bluntly conical. Eggs double shelled, 0.10S by 0.08 mm. Embryo 0.092 by 0.072 mm. Nymph when encysted coiled in a more or less complete circle with ventral surface convex (Fig. 263) occurring in a great variety of hosts. Sambon lists sixteen positive cases from man; the list would doubtless be greatly extended by full records from Africa where the parasite certainly is common. It may be looked for in travelers, missionaries, and others who have visited the in- fected region. Discovered in a West African python by Dr. Savage and described by Dr. Wyman of Boston, it has been found since then in other pythons and puff adders throughout the Ethiopean region. It is the larval form which occurs in man, encysted in the liver, lungs and mesenteric glands. This species is frequently reported in Africa and once from Jamaica in a recently introduced slave. Other records, such as those of Flint from Missouri, Sanchez from Mexico, and Osier from Johns Hopkins Hospital, are at least in fault in diagnosing the species pre- sent ; in some of these cases it is clear that the para- site did not belong to this group at all. Successful artificial infection experiments were carried out in Africa on natives suffering from sleeping sickness. Porocephalus moniliformis (Diesing) Adult = Pen- tastomum moniliforme Leuckart. Much like the former species but slenderer, tapering more caudad. Male 2o mm. long, 2.5 mm. broad, with twenty-six rings; female with twenty-eight to thirty-one, 70 to 90 mm. long, 4 to 7 mm. broad in maximum. This species belongs to the Oriental region: India, China, Philippines, East Indies, etc., where the adult occurs in the pythons and the nymph encysted in many hosts, including man. Of the two human cases on record, that of Herzog and Hare concerns a native Filipino who died in Manila of tuberculosis. A single parasite was found in the liver at necropsy. Acarida. — The mites are throughout of small size, even the largest ticks attaining a length of only half an inch and the majority being but a fraction of this. The body is circular or oval in outline, with flattened ventral surface and arched dorsal. Ordina- rily it manifests no separation into parts, though in some forms a distinct groove makes two regions distin- guishable. While the skin is commonly marked by transverse striations or folds, traces of metameric segmentation are only rarely to be found. The chitinous covering is frequently provided with plates or shields, and bristles are characteristically pres- ent. A small projection (rostrum or capitulum) carries the mouth parts, which are often more or less fused into a beak and modified for biting, piercing, or sucking. As mouth parts are distinguished (1) the mandibles or chelicerae; (2) maxillipeds or pedipalpi, the most prominent part of which are the maxillary palps, jointed, highly mobile structures, located at the sides of the mandibles. The lower lip (hypos- toine), anterior and inferior to the maxilke, is ordina- rily fused to their bases. The four pairs of legs, composed of from three to eight joints each, are terminated by claws, bristles, or suckers of various sorts. They may be attached directly to the skin or reinforced by a chitinous framework (epimeres) which may join to form a median ventral ridge (sternum). A special respira- tory (tracheal) system is lacking in most parasites, though present in some; it opens by paired stigmata with sieve-plate coverings (peritremes) the location of which is characteristic for various groups. Eyes are also usually wanting in the parasitic forms. The separate sexes may be distinguished generally by difference in size; in some forms a marked sexual dimorphism exists. The genital orifice is surrounded by a system of chitinous thickenings known in the male as the epiandrium and in the female as the epigynium. The vulva serves as birth opening, whereas a special copulatory orifice occurs at the posterior end of the abdomen. The acarida are usually oviparous, and from the egg emerges a hexapod larva which metamor- phoses into an octopod nymph, and finally by the development of the sexual organs becomes adult. This metamorphosis is accompanied by a variable number of moults, and in the SarcopticUe by histoly- sis and complete regeneration of the animal at each ecdysis. The following table, taken -from Railliet, will be convenient in recognizing the various sub-orders and families: o> No tracheae. Legs with epimeres. No trachea?. Astigmata. Legs with epimeres. Trachea? opening in the anterior portion of the body, atro- phied in the aqua- tic forms. Prostigmata. Legs with epimeres. Two pairs of legs. Palpi unarmed. Mandibles styliform. J Four pairs of legs. ] Palpi uncinate. [ Mandibles styliform. J Palpi joined at base, i unarmed. Mandibles chelate. J Palpi free, unarmed, i antenniform. M ri in li 1 ill--- chelate Palpi free, armed (rapaci). M andibles with, hooks, or styliform. Trachea? opening in the posterior por- tion of the body, at the base of the legs, sometimes atro- phied. Metastigmata. Legs without epi- meres. Palpi free fusiform, mandil ilea chelate. Palpi free, filiform or valvate. Mandibles, pseudo- chelate. Palpi free, filiform. Mandibles chelate. Phytopticke. Demodicida?. Sarcoptidae. Bdellidfe. Murine: Halicaridae. Freshwater: Hydrachnidse Terrestrial: Trombidiidffl. Oribatidse. Ixodidx: Argasidse. Gamasidae. DemodicidcB (the Follicle Mites). — Small, elongated mites; anterior region undivided, in adult with rostrum and four pairs of short legs; the posterior transversely striated, without appendages. Tracheae, stigmata, and eyes wanting. No marked sexual dimorphism. Oviparous. Larva without legs or with three pairs of tubercles, nymph with four pairs of. rudimentary legs. Parasites of hair follicles and sebaceous glands of mammalia. Only a single genus with several Species. Demodex folliculorum (G. Simon) =D. foil. var. hominis auct.; Steatozoon foil, E. Wilson. Rostrum short, anterior region of body approximately one- third of total length. Egg eordiform, 0.06 to 0.0S by 504 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arachnida Fig. 264.— Dem- odex canis. Ven- tral view of female and of egg. X 100 diameters. (After Megnio.) nil I to 0.05 mm. Male 0.3 mm. long; female 0.38 mm. to 0.045 nun. long. This form, which presents a characteristic appear- ance ( Fig. 264), is a common parasite of the sebaceous elands of the human skin. It is easily discovered in the sebum from the glands of the nose, lips and forehead; also in the ceruminous and Meibomian gland . and from the abdominal and pubic regions. Normally the mites resf in the gland, head inward (Fig. 265), and but a few arc presenl m each V gland; occasional increase in numbers is said tn give rise to stoppage of the dud and from five to twenty may be found in a comedo plug. The state- ments of some authors, according to which these parasites occur in two- thirds of the persons examined, are held by other investigators to be far beyond the usual percentage of in- fection. Precise data are lacking. Henle, who discovered this species in 1841, obtained living specimens of the mite from a cadaver six days after death. In spite of the fact that this species is difficult to distinguish from related forms of the dog, cat, and other domestic animals, with a single doubtful exception, no case of infec- tion transmitted in either direction is on record, and all efforts to accomplish this experi- mentally have failed. Although D. cants gives rise in the dog to a serious dermal disease (Fig. 265) which is rather difficult to handle, no similar difficulty is reported for man with D. folliculorum, even in the case of those individuals habitually regardless of personal cleanliness; and an etiological relation between these mites and acne, as maintained by various observers, has not been satis- factorily demonstrated. Sarcoplidce. — Small, pale mites, w r ith soft body, not elongated, separated into two regions by a more or less distinct transverse groove. Mandibles chelate, maxillary palpi styliform. Four pairs of five-jointed legs with epimera,. in two groups corresponding to the regions of the body, terminal joints (tarsi) with one or two claws, a sucker, or both, or with long bristle. Trachea? wanting. Sexual dimorphism general. Met- amorphosis with hexapod larva and two nymphs, oft i'n complicated by the appearance of a h\ r popial nymph. Of the seven sub-families only the Sarcoptinae or itch mites, and the Tyroglyphinae or cheese mites, are of importance here. Sarcopiince (the Itch Mites). — Parasitic mites with transversely striated integument, with campanulate pedunculate tarsal sucker, often atrophied and re- placed by bristles on the third and fourth pairs of legs. Vulva transverse. Found in the skin of mammals and birds, where they produce the various forms of scab and itch. Sarcoptes (the Itch Mite of Mammals). — Body round or slightly oval. Rostrum short, and thick; posterior feet entirely or nearly hidden by the body. Tarsal suckers with long, simple peduncle; in female on the first and second pairs of legs, in the male also on the fourth pair. Anus terminal. Some authors distinguish but a single species with numerous varieties; it seems better, however, in spite of the often insignificant and in part inconstant specific differences thus far known, to follow the later authori- ties in regarding these forms as different species, even though physiological characters must still be used in part for their distinction. They apparently do not interbreed, and certainly are permanent only on the appropriate host from which in some cases they can- not be transferred to any other, even for a short time, A earns scabici de though usually such transfer results in temporary existence without the di ea e reaching a serious si i and often disappearing spontaneou lv . Sarcoptes scabiei (de Geer) (the Human Itch) Acarus siro, .1. exulcerans, Linn. Geer; Sarcoptes hominis Hering; S. se.var. /mini n is Megnin. Dorsal scales pointed, longer t ha n broad. Anterior projections of e p i a n d r i u m short , scarcely reaching the epi- meres. Posterior spines long, pointed. Male (Fig. 267) 0.2- 0.24 mm. long, 0.1.5-0.2 mm. broad: female (Fig. 266) 0.3 to 0.45 mm. long, 0.25 to 0.35 mm. broad. The history of the disease caused by t he itch mite is con- nect e d with some of the most momentous dis- putes in medi- cine. The com- plaint is recorded in the earliest writings, ami the mite may have been known to Aristotle; but the Arabian physi- cians in the twelfth century were the first to state clearly the existence of a minute charac- teristic animal which could be removed from the skin and "cracked" on the finger nail. FlG o 63 ._ Transectioll of skin o( Dog , Ine galleries Showing Demodex canis in Position in Hair bored in the skin Follicle and also in Sebaceous Gland. (After were discovered Laulanie, from Neumann.) e. Epidermis; in the fourteenth /"• hair follicle containing two hairs, p, the centurv and the hulbs of which can be dislinquished at 6 '(--> Hn nrilinrl a "d &' I at the points, a, ai, aii, aiii and a&, H " escrlDe J? the follicle has undergone dilatation, by and figured reas0 n of the accumulation of the follicle clearly in the mites, d\ sb, sebaceous glands one of which s e v e n t e e n t h , («&i) contains the mites^ sd, sudoriferous while in a letter glands. X 40 diameters, to the famous Italian anatomist Redi, in 16S7, Bonomo and Cestoni gave a precise description and figures of the mites and their eggs, inferring correctly that the animals were of separate sexes and were the actual cause of the disease, so that a cure depended upon their complete destruction. Others of prominence in dermatology, however, attributed the trouble rather to "destructive juices," either denying the existence of the mites or their relation to the itch, or holding that a poison was inoculated into the blood by their bite. Early in this century the French Academy offered a prize for the rediscovery of the mite, whereupon a certain Dr. Gales 505 Araclinlda REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 266. — Sar copies seab- iei, female, in Dorsal Aspect. X 100. (After Fiirsten- berg.) E aimed off cheese mites on a learned jury, pocketing oth the medals and the prize! Finally, in 1834, Renucci demonstrated in Paris the method by which Corsican women were accustomed to remove the mite on the point of a needle from the end of its tunnel, and thus established its actual presence in the disease. The male was discovered by Kramer in 1S45, and the pathology of the disease established upon unimpeach- able experimental and clinical evidence particularly by Hebra. The mite appears to the naked eye white and glisten- ing, and was aptly described by Bonimo as like a little bladder of water. Viewed under the microscope there is seen a tortoise-shaped head with a pair of short, heavy legs on either side, which have a framework of chitin- ous bands like the garters of an Italian bandit. The third and fourth pairs of legs are concealed under the posterior margin of the body. The male is much smaller than the female and has the fourth pair of legs terminated by a sucker instead of the bristle which is on the fourth pair in the female. There is also on the ventral surface of the male a complicated chitinous frame-work wanting in the female. The human itch mite lives in the skin in which the female tunnels an irregular winding passage, where she passes her entire existence (Fig. 268). These burrows vary in length from a few millimeters to two or more centimeters and are excavated preferably where the skin is thin, as between the fingers, in elbow or knee joint, on mamma? or penis. The gal- lery, directed first downward through the stratum corneum, is extended through the softer cells of the Malpighian layer just above the papilla?. Eggs and fecal matter fill the most of this tunnel, at the inner end of which may be found the female. The male is much rarer; its existence is passed on the surface of the skin, hiding under scales and in furrows. After an incubation of only a few days there emerges from the egg a hexapod larva, which bores through the roof of the tunnel and gains the surface of the skin, where after three or four moults and the acquirement of a fourth pair of legs the development of the sexual organs is com- f)leted. Copulation is fol- owed by the last moult on the part of the female. The latter now pregnant, begins the construction of a gallery in the epidermis (Fig. 2i>9) and once buried in the skin, the recurved dorsal spines prevent her escape. This species is probably distributed over the entire world; it is very common on the Continent and among the poor in England where it constitutes eight per cent, of dermatologieal cases in hospital practice and three per cent, in private practice. It is much rarer in the United States and is inn I frequent in the East; in New York Bulkley had two per cent, in the hospital and one-fourth of one p«-r cent, in private practice. In Boston White noted an increase from nine cases in 1880 to 16.5 in L888. Of 318,500 cases recorded by the United States Dermatologieal Association within a period of Fig. 267. — Sarcoptes scabiei, male, in Ventral Aspect. X 100. (After Fiirstenberg.) a little over twenty-one years (from July, 1877, to January, 1898), it was found in 3.66 per cent, of the total number. Although rare under ordinary circum- stances, it increases rapidly under conditions of crowd- ing; thus in 1S93, the year of the Chicago Exposition, 901 cases were reported in the United States, while in 1895 the total was only 3S3 cases. Where such crowd- ing is combined with faulty sanitary conditions, it becomes epidemic in a severe form. Thus during the Civil War, the "army itch," "Jackson's itch," and Fig. 268. — Sarcoptes scabiei. Impregnated female (s) in cunic ulus. i Ain-r Ilaillu-t; somi-diagrammatic figure adapted from Ger lach.) oe, oe', oe", Eggs, those farther away from the mite being older; c, an empty egg shell; o, orifice through which a larva has escaped; e, excrementa. "seven years' itch," which are merely aggravated forms of the disease, followed the movements of the troops. The disease is produced by the transfer of the parasite by actual contact from an infected person to one not infected. Such infection must transport both sexes, or at least pregnant females, and under such conditions that they can successfully form bur- rows. In spite of the fact that in large continental hospitals and clinics, yearly thousands of cases are treated and handled by nurses and students without any precautions whatever in the way of disinfection, no trouble is experienced from the disease. Infection is easily and most commonly brought about by long-continued and intimate contact, and the nocturnal habits assigned by some to these mites 506 REFERENCE BANDBOOK OF THK MEDICAL SCIENCES \r.n hnlil:i arc due to their increased activity under the influei of the warmth of the bed. The disease is also mo I imon among men and of such classes and occu- pation- as arc wont to sleep together. A transient infection may be induced by the transfer of this species to the horse, dog, or ape, but the cat is ap- ently immune toward it. The itch mite excites at first only a moderate irritation, which gradually grows in intensity and becomes an extensive pruritus, accompanied by ecze- niaiic inflammation with the formation of papules and vesicles. The malady increases in severity with dura- tion, and especially as the result of scratching, until %faJ\S vv \y^< i^AA/J 8 c g^ Fig.269. — Acarian Furrows, a, Position of mho; A, themitehas gone down beneath the epidermis; B, the mite has commenced to dig a longitudinal burrow, and the place (/) where it was in A, has by the growth of cells come up nearer to the surface; C, the point (/) pecies, which normally attack- the swallow, has been known to pass from the nests under the eaves into sleeping-rooms and to attack the occupants of the r i giving rise to severe itching. Holothyrus coccinella, which is found on the island of Mauritius, is a serious pest of the ducks and g( I e. It attacks man frequently and incites an acute derma- titis. H often migrates into the buccal cavity with great danger to children especially. Several other Gama ids have been reported in Isolated cases from the human host. Trombidiidce (The Harvest Mites). Soft-skinned, velvety, often highly colored mites, with tracheae opening at the base of the rostrum or on the cephalo- thorax, and usually with eyes. Sucking rostrum with styliform mandibles and uncinate palpi. Legs six- jointed, terminated by a double hook together with a .small sucker. Of the large number of terrestrial mites included in this family only a few species are parasitic, but some of these, though only occasionally at lacking man, are yet among his most disagreeable chance par- asites. Doubtless many other species than these noted here may be found to attack him in one place or another; it is desirable that accurate data regarding all such species be on record. According to Joly and others, these mites are the passive carriers of infectious agents, but Nuttall doubts this and thinks the cutaneous affections produced by their presence on the skin are due to irritating secretions of the mites. The effect Megnin pro- duced by binding on the skin the dead bodies of one of the most toxic species tends to support this view. To secondary bacterial infection brought about by scratching the skin and to reduced vitality of the latter referable to the mites, are to be attributed the extreme effects manifested in the formation in some cases of ulcerous and running sores. Pediculoides ventricosus (Newport) = Hcteropus Vi ntricosus Newport. Male 0.12 by 0.0S mm., oval, with six pairs of bristles and a pyriform plate on the dorsal surface. Female cylindrical, 0.2 by 0.07 mm., with four pairs of bristles. When gravid with poste- rior region inflated to a sphere filled with developing eggs, nearly 2 mm. in diameter, viviparous. This form lives parasitic on insect larva?, particularly those of grain. Numerous cases of accidental para- sitism on grain shovellers, or those otherwise engaged in handling it, are reported from different parts of France and Germany. The bite of the mite produces insufferable itching and excites a considerable cutane- ous inflammation. Similar troubles have been produced by Tarsonemus intectus Karpelles from Bulgarian grain and Pi/ymc- phorus uncinatus (Flemming) from Russian wheat. Chelytus eruditus (Schrank). Pale, rarely reddish in color, with bifid hook on the palpi. Length, 0.S mm. This mite occurs at times in old books, or among dusty rags, but more commonly in stables, chicken or pigeon houses, in old feed bins and in tobacco store- houses, or wherever mites are abundant. In spite of 509 Arachnida REFERENCE HANDBOOK OF THE MEDICAL SCIENCES its predacious habits, it has not been known to attack man, and its presence in fecal mailer and in pus collected from the ear, as reported in various medical works, was undoubtedly due to accidental intro- duction. When St. Peter's in London was restored, this form swarmed in myriads over workmen engaged in repairing the ancient tombs. Nephrophages sanguinarius Miyake et Scriba is a related species which two Japanese physicians found daily in the bladder of a patient afflicted inter alia with hematuria. Although its presence was noted for a week, its relation to the disease was by no means established. They showed that it was living in the bladder, but had to leave undetermined how it reached that location. This may have been due to contamina- tion of instruments and such contamination in one way or other serves to explain most similar cases. The mites which van der Harst discovered in urine he showed had really come from the cork of the bottle in which the sample had been sent to him, and similar confusion has arisen in other cases. Yet such mites may be, if rarely, still sometimes actually, endoparasites of man. Miyake and Sciba in Japan found one species in a cyst of the wall of the vena cava; and Castellani in Uganda discovered another in a cyst of the omentum of a negro. New- stead and Todd described mites of this family as endoparasites in apes, and among birds such an occur- rence is very common. Leptus irritans Riley. Color brick or blood red; legs terminating in two stiff hairs. Mandibles tridentate at end. Length, 0.24 mm. (Fig. 273, C). Adult unknown. This is the larval form of some unknown adult, not a plant-feeding species, as formerly believed but of a form parasitic in the adult condition on grasshoppers and other insects. The allied European species are found on mammals, birds, and Arthropods. The latter, especially the Insecta, appear to be the normal hosts. The American larva under consideration occurs in enormous numbers on grass and herbage and its normal habits are unknown. But under temptation it adopts a habit as fatal for itself as it is uncomforta- ble for man. Brushed from grass or shrubbery on to human clothing, it finds its way to the skin into which it burrows until entirely buried, following usually the duct of a sebaceous gland. The skin forms a fibrous sheath about the proboscis of the larva in the midst of a dermal swelling the size of a pin-head. The re- sultant irritation varies considerably with the indi- vidual and in some cases produces extreme torture. The inflammation gives rise to a large red blotch with paler spots and spreads rapidly when the body is scratched in consequence of the itching. This mite occurs over much of the eastern, central, and southern portion of this country, extending in the Mississippi valley as far north as central Iowa and being very abundant in parts of Indiana, Illinois, and Ohio, even as far north as the islands in Lake Erie. In Washington it is abundant from June throughout the summer, and farther south the season is longer. Osborn speaks of the same species as annoying in Southern Mexico in January. Those who are sus- ceptible to the pest are accustomed, on returning from field excursions, to resort at once to a hot bath with strong soap, or to the use of a wash of dilute carbolic acid to kill the mites before they become embedded in the skin. Dilute alcohol is also recommended. At this time it is also possible by close scrutiny to recognize the mites in the center of the inflamed area and to remove them individually, doing away thus with the subsequent discomfort to a large extent. It is interesting to note that the invasion of the human skin causes the death of the mite and prevents it- reaching maturity, a perverted habit being thus fatal to the species. As a result the adult form is not known, but assumed as possibly one of the genus 7 otnbidium. 510 Leptus americanus Riley (Fig. 273, B) is an associ- ated form, the effects of which are very similar. The Continental species is L. autumnalis Shaw. Similar forms are known from all regions: among these the one known as Tlalsahuate in Mexico, and the Colorado of Cuba deserve mention. Fig. 273. — B, Leptus americanus. Greatly enlarged. (After Riley.) C, Leptus irritans. Greatly enlarged. (Alter Riley.) (In B and C the dots underneath indicate the natural size.) The Kedani mite of Japan also known as Tsutsuga- mushi or Akamushi, is a small hairy mite with two red eyes; it measures 0.1(3 to 0.38 mm. long by 0.1 to 0.2-1 mm. broad. When the mite is torn in removing it from the skin or by accident, a small blister with a painful swelling is formed at the site of the bite. This is accompanied by enlargement of neighboring lymph glands, with fever and general prostration, which in extreme cases leads to sudden death. Tanaka has isolated from the body of the mite a toxic substance to which he attributes the effects described. The mite occurs in widely separated provinces of Japan and is greatly feared by the populace. Telranychus moleslissimus Weyenberg from Uru- guay and Argentine, which lives normally on an aster, is of like evil repute. The case of Tydeus molestus Moniez, a blind, rose- colored mite of the family Bdellidaj or snouted mites, which was discovered on a large estate in Belgium where it first made its appearance in 1S64 after an importation of Peruvian guano, illustrates the chance introduction of an undesirable species. Each year it appears at mid-summer and remains until frost, so abundant that it constitutes a veritable pest. It throws itself on man passing through the grass or shrubbery and produces an insupportable itching, lasting several days. Ixodoidca (Ticks). — Among the ticks, which con- stitute technically speaking the superfamily Ixodoi- dea of Banks, two families are recognized: the Argasida; and the Ixodidre. The former are covered by a uniform leathery integument without a hardened shield or scutum. The Ixodicke possess such a scutum covering the entire body of the male t hough on the back of the female it forms only a small patch at the ante- rior end while the distensible posterior region pro- jects to a variable extent behind it. In the Arga- sicke the sexes are much alike, whereas the Ixodidse showed marked sexual dimorphism. Moreover the former feed moderately and both sexes change thereby only slightly in thickness when gorged. The replete females of the Ixodida? are enormously in- creased in size and changed to a shapeless round mass. Numerous other minor features in structure and habits serve to justify further the separation of the two families but may be omited here. The work (if recent years has disclosed the hygienic importance of this group since at least two important human and REFERENCE HANDBOOK OF THE MEDICAL SCIENI ES \ i.ii liin'i.i many animal diseases are transmitted specifically by tin' ticks. The Argasidse are mostly found in warm dry regions and attack primarily birds and bats, but sev- eral species seek out man when occasion offers and from their nocturnal habits as well as their flattened form when fasting they arc mistaken for bedb Two genera only arc recognized: Argas and thodoros; both of them attack man and both serve at times as transmitters of human as well as animal diseases. Mos( if not all of these species are noted for their powers of endurance, specimens having withstood absence of food and water for months and even for two to three years. This characteristic accounts for the sudden appearance of diseases transmitted by such ticks in houses or shelters that arc rarely used or been abandoned for a long period. The genus Argas is defined by Xultall as follows: y flattened, oval or rounded, with a distinct flattened margin differing in structure from the ral integument; this margin gives the body a sharp edge which is not entirely obliterated even when Hi,' tick is fully fed. Capitulum (in adult sand nymphs) entirely invisible dorsally, distant in adults by about its own length from the anterior border. On both dorsum and venter there are numerous symmetrically arranged disks, generally round or oval, more or less disposed in radial lines. Elsewhere the integument is minutely wrinkled into irregular zig-zag folds. Eyes absent. This same author recognizes six valid species and four that are doubtful among w'hich the following onlv are of importance here: Argas persicus (Oken) 1818 (Fig. 274) = Rhyn- ekoprion perscium Oken; Argas persicus Fischer de Waldheim; Argas mauritianus Guerin-Meneville; Argas miniatus C. L. Koch; Argas americanus Packard; s sanchezi Alf. Duges; Argas chinche Goudet; radiatus Railliet. Fie. L'74. — Argas persicus; Dorsal and Ventral Aspects. En- larged. (After Marx.) Body oval, widest posteriad. Margin striate with quadrangular cells. Spiracle half as wide as anal ring. Male 4 by 2.5 to 5 bj' 3 mm. or rarely S by 5 mm. Gravid female 7 by 5 to 10 by 6 mm.; when gored 11 by S.5 mm. Nymph 4 to 4.5 mm. long in first stage; 5.5 to 6.7 mm. in second stage. Larva 0.7 to 0.8 mm. in length. Egg spherical, 0.6 to 0.S mm. in diameter. Host: primarily a parasite on domestic fowl; this species has been reported also from duck. -e, turkey, quail, canary, ostrich, and once from cattle in Texas, as well as from man. After leaving the host it hides in cracks in floors or walls, or under the bark of trees. Though originally described from the East and sepa- rated from our native species this form is truly the same. It is cosmopolitan in its distribution even though it is most abundant in Persia where its frequence and bad reputation are historic. It occurs widely on the North American continent and in the United States has been recorded often from Texas and also from New Mexico, Arizona, California, and Florida. In many places it is a serious fowl pest. Arga / IS is popularly known in this country as the fowl tick, or adobe tick it, Arizona and New Mexico. In Persia it is called the Miana bug and is said to behave like the bedbug, being at times so numerous as to drive out the inhabitants from infested villages. The early reports regarding the fatal re ult attending its bites are probably exaggerated and il has not been shown that this | Veys to man any specific infectious disease as it does to fowls to whi< h it transmits Spirochceta < thi cau e of a fatal malady capable of destroying all fowls within a in the course of a few day-. 'J here is, however. evidence that in man also its bite ] lui il effect . Mans, m states that miana fever is certainly trans- mitted to man by this tick and this view is generally found in scientific literature, but Nuttall questions the truth of the statement. In cases, especially a 1 1 mug infants and children, or individual 3U Ceptible to urticaria fact it ia. the bite causes edema of the part, or even of the entire body, together with intense pruritus lasting several days. Argus reflexus, the common European species, regularly infests pigeon coops, from which it enters dwellings, and has been found in large numbers in house lofts, and even in old churches in which pigeons had been kept. It seems to have grown rarer in recent years. This tick has been shown capable of transmitting pyogenic bacteria to healthy persons when it has previously had access to the skin of per- sons suffering from furuneulosis. Argas brumpti infests the burrows of the porcupine in Africa and attacks men sleeping on the ground; it hides in the dust during the daytime. Argas chinche, troublesome to man in Columbia, is probably identical with Argas persicus, described above. Ornithodoros Koch, 1S44, is difficult to distinguish from Argas and is regarded by some authors as hardly more than of subgeneric rank. It includes eleven well established and several doubtful species: O. savignyi, the type species, occurs in Africa where it attacks man as well as various domestic animals. Ornithodoros moubata (Murray) = Argas moubata Murray, Ixodes ?noubata Ornithodoros savignyi, var. cazca Neumann. Adult 8 by 6 or 7 mm.; gorged females up to 11 mm. long. Nymph in first stage, 1 by 0.87 mm. Egg 0.9 by 0.S mm. Much like 0. savignyi, but less hairy and easily distinguished by absence of eyes and details in the structure of the appendages (Fig. 275). Hosts: Domestic animals generally, also monkey and man. Man appears to be the chief host. The species is widely distributed in Africa south of the Sahara. It hides in the dust or sand and attacks animals at their resting places. Ticks are found particularly along much traveled highways and less frequently if at all in isolated native villages. This may be due to the temporary character of native huts and their frequent abandonment. Along the Congo the rest houses of native travelers are badly infected. The species is known as the papaze and is evey where plentiful in the Arab houses, where they hide in cracks and crevices of the walls, or even in thatched roofs. Livingston noted that its bite is painful and that the sensation persists and he also referred to the well- known fever that follows the bite. This disease is the African relapsing fever or human tick fever found through Eastern and Central Africa, the Congo, and Angola. It is caused by Spirochceta duttoni which is transmitted by bite of the tick and multiplies in the human blood where maximum numbers are found during the febrile attacks. These follow five to ten days after a non-immune has been bitten. When a female tick sucks blood containing Sp. duttoni, the organism migrates into the ovaries of the ticks and infects the undeveloped eggs. Thus the 511 Arachnlda REFERENCE HANDBOOK OF THE MEDICAL SCIENCES next generation of ticks is infected and the parasites are transmitted when the new nymph in the first stage feeds on the blood of a new host. It has been shown that the spirochete is even transmitted through the ova to the third generation of ticks, although the second generation had been fed on non- infected blood. Such infected ticks will naturally transmit the disease by their bites. So-called coccoid bodies or granules demonstrated in the tick Fig. 275. — Ornithodoros moubata, female, X3; dorsum and venter; specimen from British Central Africa. (After Nuttall.) ovary constitute the infective agents; their nature and biology have not been fully elucidated. 0. moubata has also been considered capable of transmitting Filaria perstans to man, and Wellman was able to follow in part the development of such filaria embryos in this tick. 0. coriaceus from California and Mexico is feared by natives because its bites are severe and heal very slowly. 0. turicata from New Mexico, Arizona, and California, as well as further south, attacks pigs, cattle, and man. It may cause serious injury by its bite ami Duges says people are reported to have died therefrom. 0. talaje is another species in the same region that at times attacks man; it infests normally old houses and like other species comes out at night to bite. 0. thalozani is the sheep bug of Persia, Fig. 276. — Rostrum of Ixodes hexajronus, female, from below. X50 diameters. (After Delafoud, from Railliet.) ■which also attacks man and may transmit disease. It is locally said to be very dangerous to man. 0. megnini occurs chiefly on the ears of the horse, OX, and ass, and has been recorded from the human cur in Mexico. The species has been reported from the Gulf Stales, and as far north as Nevada, Idaho, and Iowa. It has been found as a chance parasite in the human car in New Mexico and Arizona but was readily removed by introducing a pledget of cotton moistened with chloroform. Most of the cases on record are among children in infected regions. Intense pain is caused by their presence in the human ear but so far as known no more serious consequences. The Ixodidae are most easily recognized by the fact that the beak, technically designated the rostrum or capitulum, is not hidden below the anterior margin of the body as in the Argasidae but projects con- spicuously beyond it. The capitulum (Fig. 27G) consists of (a) the flattened maxiUo-labial hypostome, ib) two maxillary palps, (c) two elongated mandibles inflated at the base but flattened toward the tip. The hypostome and the terminal joint of the mandibles are armed with retrorse spines or teeth. The two spiracles lie just posterior to the coxae of the fourth pair of legs The Ixodidae. are highly specialized parasites. Most of them are parasitic on wandering hosts and all stages are found on the same host. When the males occur alongside of the females, both sexes are characterized by the possession of hypostomes similarly well armed with prominent teeth. Species that are parasitic on hosts with more or less fixed habitats display less highly specialized parasitism iu that the males do not occur on the hosts and do not possess armed hypostomes. The male feeds sparingly Fig. 277. — Ixodes ricinus, L., male, in Ventral Aspect. (After a drawing by A. Dampf.) X 16. on the host but the female gorges itself with blood until the leathery distensible hind body has swollen to the size of a castor bean which it resembles strongly. Such engorged females drop to the ground and after a quiescent period spent in hiding, the huge masses of eggs are laid. The hexapod larvae, which emerge after a variable time depending on temperature, climb to the tips of blades of grass, bushes, and other vegetation, and attach themselves to hosts from which a meal of blood is taken. Once satiated such a larva falls to the ground and undergoes a metamorphosis. The octopod nymph repeats this history on a new host and then metamorphoses into the adult which again seeks out a host and completes the life cycle. The duration of this cycle s about six months under most favorable conditions but may require two or three years. These ticks, naturally abundant in woods and underbrush, or in high rank grass, select their hosts largely by chance. .Many of them may occur on man and the frequence of this depends chiefly on the abundance of the tick; secondarily, its special habits govern its appearance on the human host. The 512 REFERENCE HANDBOOK OF TIIK MEDICAL SCIENCES Araclinlda species occurring cm 1 1 1; :n i have iml been recorded with desirable accuracy. They arc fre< |ucnt ly found Oil travelers as well as cm workers in wooded districts and there removal is effected by simple methods without medical assistance. I'sually I heir presence is not fol- lowed by any untoward results. Many authors report psoriasis-like eruptions and phlegmonous inflammation following tick bites. Yet a lick may hang on for days without being per- ceived and experiments to inoculate germs through ink bites have thus far proved negative. Whenever the tick is forcibly removed and the rostrum left imbedded in the flesh of the host the wound is painful i much more serious. A drop of turpentine. benzine, petroleum, or even oil or melted butter, placed on the head of the tick, will usually cause it to loosen its hold and drop from the skin. Sometimes ticks penterate beneath the skin of the host. Several oases are on record in which living ticks have been found in cysts or tumors on the human skin. These reach the size of a nut but are easily removed. Texas fever in cattle is transmitted by ticks and dipping is practised extensively to relieve these hosts of the infecting agents. Nine genera are recognized; of these only Ixodes, I), rmacentor, and Amblyomma are of especial signifi- cance here. Ixodes. — Anal grooves surrounding the anus in front. Xo eyes; without festoons. Spiracles round 278. — Ixodes hexagonus, male, in Ventral Aspect. X13. (After Neumann.) or oval. Sexual dimorphism pronounced. Ventral surface of male covered by non-salient plates. Type species: /.codes n'n7!t/.s(L)( The Cast or BeanTick) =/. reduvius of many writers. Male brown, oval, larger posteriorly, 2.5 mm. long by 1.5 mm. broad. Female 4 mm. long and :> mm. broad, or when gorged 10 to 11 mm. long by ti to 7 mm. broad, ashen gray tending to brown or yellow. This species is abundant in Europe and occurs throughout the United States from Pennsylvania, Kansas, and California to Florida and Texas. It occurs apparently by preference on sheep and cattle, though frequent on the horse, rabbit, many wild mammals, and less often on birds and reptiles. It is the chief carrier of redwater in cattle (bovine piroplasmosis) with which its connection has been conclusively demonstrated by experimentation. Cases of septi- cemia in man are recorded by European writers as the apparent result of the bite of this species, but ex- perimental work has thus far failed to confirm this view. Ixodes hexagonus Leach( The European Dog Tick) (Fig. 278). The breadth of the median plate and the shorter rostrum distinguish this from the preceding pecies. It is very widely distributed in Europe and Fig. '279. — Stigmal Plate of Male Dermacentor anderBoni. Notice the relatively large aperture and chamber and the prominent dorsolateral prolongation which forms a right angle at the caudal margin; the goblets are numerous (157) and evenly distributed, but areabsenl from the margin; the middle layer is visible. Greatly enlarged. (After ritiles.) has been reported from a wide range of hosts. It occurs in the territory east of the Rocky Mountains in North America. Canine piroplasmosis is trans- mitted by this species. Blanchard cites cases in which it has penetrated below the skin of man. Boophilus annulatus (Say), the Texas fever cattle Fig. 280. — Stigmal Plate of Female Dermacentor andersoni. Notice the acute angle formed by the dorsolateral prolongation; the anterior margin of the prolongation is broader than the caudal margin; 120 goblets are present. Greatly enlarged. (After Stiles.) tick, exceeds in economic importance all other species as the form by which Texas fever in cattle is transmitted. The organisms of this disease {Piro- plasma bovis) are transmitted through the eggs from one generation of ticks to the second or even the third, which can accordingly produce the disease in non- Vol. I.— 33 513 Arachnlda REFERENCE HANDBOOK OF THE MEDICAL SCIENCES immune animals. The larvae occur only very rarely on man. Even in Texas where the species is very abundant, accurate observers have found it on the human skin only half a dozen times in ten years. Apparently it does not transmit any germs to man here. In Africa, however, "tick-bite fever" with a fairly definite train of symptoms may follow the bite of a variety of this species. Fig. 2S1. — Dermacentor andersoni, young female. Dorsal View. (After Stiles.) Dermacentor. — Anal grooves surrounding the anus behind; rostrum short. Ornate with eyes and fes- toons. Basis capituli rectangular dorsally. Stiles has demonstrated that the stigmal plates (Figs 279 and 280, form a ready and accurate method for the distinction of the numerous species. This genus includes the species responsible for the transmission of Rocky Mountain spotted fever, and Fig. 282. Dermaeentoi andersoni, male from Montana. View. (After Stiles.) al~o several others commonly found on man in various sections of the country. The most impor- tant species uiniiiestionably is: Dermacentor andersoni Stiles (The Rocky Mountain Spotted Fever Tick) = D. venustus Banks; D. occidentalis < >f writers on Rocky Mountain Spotted I ' er. Gray to red, brown, or even nearly black. Stigmal plate large; its dorso-lateral prolongation distinct. Goblets in plate very numerous and crowded. Male 4 by 2.5 mm; female may attain 16 by 9.5 by 6 mm. when replete (Figs. 2S1 to 284). Hosts: man, cattle, horse, dog, rabbit, gopher. Habitat: Montana, and parts of Washington, Oregon, Idaho, Nevada, Wyoming, Utah, and Colorado. It is the common tick of the Bitter Root Valley. It occurs Fig. 283.- -Dermacentor andersoni, young female. (After Stiles.) Ventral View at elevations of from 500 to 9,000 feet but reaches its maximum at an elevation of 3,000 to 5,000 feet where it is often found in large numbers. The view that Rocky Mountain spotted fever is conveyed by the wood tick of that region was ad- vanced in 1902 by Wilson and Chowning. By a series of careful and convincing experiments ex- tending from 1906 to 1909, the late Dr H. T. Ricketts Fig. 2S4. — Dermacentor andersoni. male from Montana. View. (After Stiles.) Ventral demonstrated that the disease was transmitted chiefly if not exclusively by Dermacentor andersoni. This tick is especially abundant in localities having much fallen timber and underbrush. The immature stages feed upon small mammals, such as gopher, chipmunk and ground squirrel, but the adults attack only the larger domestic animals. Ricketts demon- 514 REFERENCE HANDBOOK OK Till', MEDICAL SCIENCES \ I.M lllllil I strated that guinea-pigs are susceptible to t he dis- ease; that larval or nymphal ticks contract the dis- ease by biting an infected animal and can transmit it in tin' following stage (nymph or adult); that adult ticks having acquired the disease can transmit it through tl gg to the succeeding generation; and, finally, that infected ticks occur in nature. It has been further shown that the actual distribution of the tick is much broader than the limits within which the disease occurs. This is an evident ele- ment of danger and indicates for the disease a much greater possible range than at present occupied. I here is some reason to believe that the malady is ading. This tick hibernates through the winter and on emerging seeks a host. During the period from about March 15 to July 1.5, the parasites attack man and transmit the genus of the disease. The eggs laid by the earliest mature females may develop to adults by September, but ordinarily this generation does not progress so far and hibernates during the second winter, thus repeating the history of the previous general ion. The large majority of these ticks re- quire two years to finish out the life cycle completely and siime take even three years. At present the virulent form of the disease with a death rate of about seventy per cent, is confined to the Bitter Hoot Valley. Measures have been formu- lated for the restriction of this form of the disease to that territory and the ultimate eradication of this tick which though only one of several that carry the disease, is the only one of the group that attacks man. The plan for the eradication of the disease, sug- gested originally by Ricketts, is based upon the Flo. 285. — Dermacentor variabilis, Dorsal view of male. X10 (After Osborn.) practical restriction of the adult ticks to the larger domesticated animals. It is favored by the limited population and the isolation of the region. It Consists in dipping all live stock, or in' hand treat- ment of such as cannot be dipped. The plan de- mands at least three years for its execution. Even if more expensive and not as successful as pro- phesied, the benefit resulting would be very great. The microorganism which produces the disease and is transmitted by the tick has not been positively determined. Ricketts isolated a bacillus that may be specific, but the question is still sub judice. D. andersoni is easily confused with D. venustus of Texas under which name it has generally been included, and with I), occidentahs of California, another species which occupies an immediately adjacent range. Stiles (Public Health Repts., July .;, L908) states tin- differences which are adequate for the separation of the three species. Fortunately it appears that neither of these closely related species and contiguous species' can transmit the Rocky Mountain spotted fever. The Pacific Coast Tick, Dermacentor occidentalis Marx, is limited in distribution to western Oregon, California, and probably .Mexico, where it is the most common tick. Abundant on live stock, it occurs often on man. especially during the rainy season when it is most numerous and the source of great annoyance. It is often confused with the previous species but, readily distinguishable by numerous red points among the white markings. The American dog tick, Dermacentor variabilis Say (Fig. 285), is the most* common species east of the Mississippi River; its range extends from Labrador to Florida. It displays a strong tendncy to attach tself in the ears of the host. No evil consequences are known to follow its attack on man. Amblyomma and Hyalomma are readily separable from other ticks by their long palps. The latter, found in Africa, is the agent in transmitting various piroplasmas in domestic animals, including the camel and dromedary. The former includes two important American forms and may be distinguished by the absence of anal plates in the male. Each of these species are frequent on man. The long beak enables it to maintain a firm hold. The severe results follow- ing its attachment to man in some cases appear to be due to the introduction of bacteria. In Africa it gives rise to a definite train of symptoms and the condition is designated "tick-bite fever." The disease affects new comers and old residents appear to have acquired immunity. Amblyomma americanum Koch (The Lone Star Tick) = Ixodes unipunctata Packard. Male: body brownish red, oval, much elon- gated posteriorly, 3 mm. long, 2.5 mm. broad. Female (young) : colored like the male with a white spot on the back of the living animal. Length 4.5 mm., breadth 3 mm., increasing in gravid fe- males to 8 by 12 mm. (Fig. 286). This characteristic American species occurs from Labrador to Florida and Texas and is known from South America as well. It is common on cattle in the south- ern part of the United States, and is reported from other domesticated as well as wild species. Packard reports a case in which a specimen had penetrated into the arm of a young girl, forming there a tumor. It is said to be very annoying to man in the warmer portions of the country, and a corre- spondent in Texas writes that he removed several females from his own children in one evening. Amblyomma maculatum Koch, the Gulf Coast tick, occurs along the Gulf Coast, especially in Louisiana and Texas. It extends far south into South America. In size and general appearance it resembles the pre- vious species but lacks the bright metallic star on the shield of the female Lone Star tick. It is more in- clined to attack man than any other North American species, except the Rocky Mountain spotted fever tick. Henry B. Wabd. Principal Articles Used. Braun: Die thierischen Parasiten des Menschen; vierte Aufl.. Wiirzburg, 1895. Canestrini und Kramer: Demodicidie und Sarcoptida 1 . Das Tierreich; 7. Lief., Berlin, 1899. 515 Fig. 286.— Ambly omnia americanum Koch, Adult female. (Original.) Arachnida REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Darling and Clark: Linguatula serrata (larva) in a Native Cen- tral American. Arch. Int. Med., 9; 401-5, 1912. Hessler: An Extreme Case of Parasitism. Indiana Academy of Science, 1893; also Amer. Naturalist, vol. xxvii., pp. 346-52, 1893. Megnin: Les parasites et les maladies parasitaires, Paris, 1880. Neumann: Parasites and Parasitic Diseases of Domesticated Animals. Translated by Flemming, London, 1892. Revision de la famille des Ixodides. Mem. Soc. Zool. France, vol. ix., pp. 1-44; X., pp. 324-420; xii., pp. 107-294, 1S96-99. Nuttall: Insects, Arachnids, and Myriapods as Carriers of Dis- ease. Johns Hopkins Hospital Reports, vol. viii., pp. 1-154, with 3 plates, 1899. Nuttall, Warburton, Cooper, and Robinson: Ticks, A Mono- graph of the Ixodoidas. 3 pts. Cambridge, 190S-1911. Osborn: Insects Affecting Domestic Animals. United States Dept. Agr., Div. Entom., Bull. 5, N.S., 1S96. Railliet: Traite de Zool. Med. et Agric, 2me ed., Paris, 1893-95. Ricketts: Investigation of the Cause and Means of Prevention of Rocky Mountain Spotted Fever. Also other important papers by same Author Reprinted in Contrib. to Med. Sci., Univ. Chicago Pre-., 1906-08: reprinted 1911. Riley: Poisonous Insects. First edition Reference Handb. of the Med. Soc, Nov York, 18S7. Salmon and Stiles: Cattle Ticks of the United States. Ann. Rept. Bur. An. Ind, 17: 3S0-492, 1910. Sambon; Porocephaliasis in Man. Jour. Trop. Med., 13: 17-23, 212-216,258-267,1910. . Shipley: Revision of the Linguatulidse. Arch. Parasitol. vol. i., pp. 52-80, 1898. Stiles: Stigmal Plates in Dermacentor. Bull. Hygienic Lab., No. 62, 1910~ Also smaller papers by the same and other authors. Araliaceae.— (The Ivy Family.) A family of some forty genera and about 400 species, widely distrib- uted through temperate and tropical regions of both the old and the new worlds. Its plants are highly ornamental, some, like the ivy, being extensively cultivated for this purpose. Medicinally, it is of note as yielding the famous ginseng. Its constitu- ents are simply aromatic and without special prop- erties. The spikenard, and several other species of Aralia, were formerly very extensively used, and are still used to a considerable extent, for these prop- erties. Some of them contain amaroids in connec- tion with their resins and volatile oils. H. H. Rusby. Araneida. — Araneida, Aranem. The order of the class Arachnida, which includes the true spiders, of which the tarantula is an example. Respiration is by means of tracheal tubes and "lung-hooks"; the abdomen is provided with spinning glands. See Arachnida. A. S. P. Aranzio, or Arantius.— Born in Bologna, Italy, in or about 1530, Aranzio acquired in time the reputation of being one of the most skilful anatomists of tin' sixteenth century. He received his medical educa- tion in part from his uncle, Bartolomeo Maggi, a celebrated surgeon of Bologna (and later physician of Pope Julius III), and in part from the illustrious Vesalius, professor of anatomy in the University of Padua. The degree of Doctor of Medicine was given to him by the University of Bologna, and very soon afterward he was called by the same institution to occupy the chair of medicine, surgery, and anatomy. For a period of thirty-three years— that is, up to the time of his death in 15X9— he faithfully performed the duties of this position. Credit is due him for a large number of anatomical discoveries. His most important publications are: " De humano fcetu opusculum.'' Rome, 1504; " Observationes anato- mical" (with the treatise on tumors). Venice, 1595; "In Hippocratis librum de vulneribus capitis conimentarius." Lyons, 1579. A. H.B: Arbor Vita;. — See Thuya. Arbuthnot, John. — Born in Scotland, near Mont- rose; date of birth not known. He took the degree of doctor of medicine at the University of Aberdeen. He began his professional career in London, and his practice grew rapidly. His reputation, however, was based rather on his literary labors than on what he accomplished in the domain of medicine. He became in turn physician extraordinary to Prince George of Denmark and one of the regular medical advisers of Queen Anne. In 1710 he formed a close friendship with the most eminent literary men of that epoch, such men as Pope, Swift, and Gay. He died in London in 1734 or 1735. He published three essays on medical topics, viz., one on the regularity of the births of both sexes; another in 1731 on the nature and choice of aliments; and a third in 1733 on the effects of air in the human body. A. H. B. Arcachon, France, (latitude 44° 7'), is situated thirty-five miles southwest of Bordeaux, in the midst of a thick forest of pine trees, where once was only a lowlying sandy desert waste. Some sixty or more years ago this waste of barren sand dunes was planted with pine trees, which thrive in sandy soil, by the French government, for the purpose of fixing the sand, which, by the action of the wind and waves, was constantly encroaching upon the country of the interior. There are nine thousand acres of these pine trees, and, owing to the noiseless sandy roads and the silent trees, there is a peculiar and, to some per- sons, a depressing stillness. Arcachon is about nine miles from the actual coast, at the south of a large landlocked bay or basin, con- nected by a narrow channel with the sea. A part of the town is directly on this bay, the Ville d'Ete\ and a part on the surrounding sand hills in the midst of the pines, the Ville d' Hiver, which is the winter resort for invalids. The features of the climate are those of a marine one, characterized by a very considerable amount of moisture, equability, and a rather mild temperature. In addition, there is the influence, whatever benefit it may be, of the pine forests, the air of which is said to be remarkably rich in ozone, and "perceptibly impregnated with the balsamic odor of turpentine." The winter climate, according to Yeo, is mild and sedative, yet not relaxing. "The calmness of the atmosphere, the silence of the forest, a certain isola- tion of the habitations, and resinous emanations from the fir trees, constitute a combination of sedative con- ditions of which not one is superfluous," says Black. ("Southwest France," Black.) Such are, doubtless, most excellent sedative condi- tions, but it would generally require a very sedate person to endure with equanimity such monotony, of which invalids too often complain, says the same author. Lalesque ("Cure Marine de la Phthisie Pulmo- naire," Paris, 1897) gives the monthly mean temper- ature for the three seasons of winter, spring, and autumn, as follows, the observations extending over a period of nine months (the figures denote degn es Fahrenheit). December 44 72 March 52.00 September ... fi!' 94 January 43.37 April 58.09 October... February 45.77 May 63.83 November . . . 51 75 From which we find the mean winter temperature is 44.62° F.; that of spring, 57.64° F.; and of autumn, 60.4° F. The daily and monthly variations are said by the same authority to be small. The average annual humidity is seventy-seven per cent, according to Lalesque and eighty-five per cent, according to Weber. 516 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arco The average number of clays of rain for the six years from 1887 to L892 is as follows: ISS7 L8S8. 117 [889 IliS IS'.IO. I7S 151 189] MO 1892 liu making an average of 152.6 days for the entire period. November and December arc the rainy monthsof tin' year. The rains are most severe during the night or in the morning, and least so toward the middle of the day. Arcachon is both a summer and winter resort; the portion of the town lying directly on the shore or the suit water lake, or basin, being the resort for summer, which is much frequented for sea-bathing, which is excellent, and for boating, yachting, and fishing. The Boulevard do la Plage runs the entire length of the town, along the sea, and on it arc situated many of the hotels, which are good. There are clubs, a casino, English or English-speaking physicians, and an English church — "all the appliances of advanced ci\ ilizal ion." The winter resort, known as the "Ville d'Hiver," is hack from the summer resort portion and separated from it by a high sand dime, between the two por- tions of the town is a large public garden. There are numerous picturesque villas hidden in the pines, hotels and boarding houses. The walks and drives in the forest offer but little variety of scenery, and one is advised to take a pocket compass in order to preserve his direction. Such a combination of pure sea air and pine forests i< applicable to various maladies, such as irritative bronchial or laryngeal catarrh, glandular and bone tuberculosis in children, and, according to Yeo ("Health Resorts and Their Uses, J. Burney Yeo," M. D.), " cases of dyspepsia complicated with hysteria, hypochondriasis, and nervous irritability." Pulmon- ary tuberculosis, however, is the disease to which the climate of Arcachon has been applied more than to any other and the place has a local reputation for the treatment of this disease. Dr. Lalesque, who has written a book upon marine climates in general and that of Arcachon in particular (Cure Marine de la Phthisie Pulmonaire, Paris, 1S97), as applied to the treatment of tuberculosis, speaks with Gallic enthusiasm of the favorable influence of such a climate upon this disease; and in ISA cases, of which 79 were in the first stage, 45 in the second, and 60 in the third, he obtained 34 per cent, of cures and 50 per cent, improved of the first stage cases; 20 per cent, and 53 per cent, respectively in the second stage; and 6.6 per cent, and 35 per cent, in the third stage. In the whole 1S4 cases he obtained 21.7 per cent, of cures and 46 per cent, improved. He applies very rigorously the "cure d'air et de repos," although his patients are not under sanatorium control, and he thinks the "cure marine" as illus- trated by Arcachon, gives results comparing favorably wilh those obtained in the mountain resorts. Undoubtedly, constant exposure in pure air is the principal climatic factor in the treatment of pulmon- ary tuberculosis, wdiatever the climate and whatever the resort, other things being favorable. "I can cure tuberculosis in any climate," once remarked the distinguished Dettweiler to the writer. Nevertheless, the high altitudes and resorts with a dryer climate have given appreciably better results, as shown by statistics. We are, however, more and more realizing that climate is only one factor in the treatment of tuberculosis, and others are quite if not more im- portant. It is only in the skilful combination of all by the expert that the best results are obtained. Edward O. Otis. Arco. — This village occupies in Austrian estimation the position which is held in Italy by San Rerao, and in France by Mentone. li is situated in the extreme southern portion of the Austrian Tyro), OH the line of the railway between Botzen and Verona, three miles distant from the beautiful Lake (larda. It lies in a valley enclosed, on all ides bul the south, by lofty mountains rising from four to seven thousand feet. The northern opening is protected by a ma of rock 370 feel high. The elevation of the village is slight, viz., from 250 to 500 feel above sea level. It is aid to be almost windless; but little rain falls and snow IS seldom seen. Its climate during the winter, which i i the time of residence for invalids, is mild and equa- ble, as following chart indicates: Observations of Temperature at Arco, Winter, 1875-1876 (From Bulenburg's " Real Bncyclopadie.") i Fahrenheit Sen!- I Month. Monthly mean ( )(■(<. 1 hT. , . Noveml ier 1 >ecember. January . . February. March .... April 59 5° 41 s° 43 ii' 45 3° 50.4° 59.0° Mean ma dmum (at noon i. Mean minimum (at noon). 71 ,9° 60 6 53. 6° 61.7° 64 I 60.2° 7.", 2° ! 42 8° 3g 41.0° 44.6° 50.0° The relative humidity is about 72 per cent. Dr. Weber (Ziemssen's "Handbuch del allg. Therapie," Bd. ii., S. 173) gives the following facts concerning the climate of the Italian lake region, and includes Arco in his list of places properly belonging within this climatic district. The relative humidity of such points he states as being between 72 and 78 per cent, during the autumn and winter months, and somewhat less than 70 per cent, in the spring season. The average number of rainy days is from 36 to 40 during the autumn, from 34 to 36 during the spring, and from 15 to 20 during the winter. Snow falls, as a rule, in this region, on not more than 6 or 8 da\ s of the year, and seldom lies for several days together upon the ground. Among the local winds which pre- vail about, all great lakes, those blowing from the north and from the northeast, are of most frequent occur- rence in this region. Fogs are rare; there are few days during which an invalid must keep within doors from sunrise to sunset; and there is less dust than is found along the Italian Riviera. The mildness of the climate is shown by the fact that the orange ripens in the open air, and the olive tree, the fig, and the pomegranate also flourish. The invalid's day is nine hours long in October, seven in November, six in December, five in January, six in February, eight in March, and the whole time between sunrise and sunset in April. The season ex- tends from September 1 to April 1. The class of diseases for which Arco is suited as a residence are affections of the chest and throat, anemia, want of appetite, nervousness, chronic catarrh of the stomach, intermittent fever, rheumatism, gout, and the scro- fulous affections of children. There are provisions for the various forms of hydropathic treatment, and an Oertel Terrain-Cur. The drinking-water is of good quality, and the accommodations are said to be comfortable and easily obtained. There are many attractive walks and pleasant excursions in the neighborhood. Weber classes Arco as among the lowest Alpine climates and says its winter climate is "sufficiently mild for persons with stationary phthisis, or con- 517 Arco REFERENCE HANDBOOK OF THE MEDICAL SCIENCES valescents from the same disease, and also for those whose object is only to find change and a sunny climate." All eases of pulmonary disease suitable for the medium and higher altitudes would of course be suitable for this climate, which offers favorable con- ditions for the open-air treatment; and, after all, this is the principal factor in any climatic treatment of pulmonary tuberculosis. For the above account of Arco the writer is in- debted to Dr. Huntington Richards' report in a pre- vious issue of the Handbook, and to Roe's "Health Resorts and the Bitter Waters of Hungary." Edward U. Otis. Arctic Springs. — Trempeleau County, Wisconsin. Post-office, Galesville. Hotels in Galesville. These springs are situated near the village of Galesville, at the terminus of a branch of the Chicago and Northwestern Railroad. The springs are at the head of a small lake called "Marinuka," while the village is at the foot, about a mile away. During the summer a small steamer carrying fifty passengers plies between the two points. The location is 750 feet above the sea level. The country surrounding the springs is broken by ranges of elevations called "bluffs," between which are beautiful and productive valleys from one to three miles wide. The main val- leys are intersected by smaller depressions at inter- vals of about a mile. All of these valleys contain clear trout streams coursing down their centers. This peculiar conformation gives the country an aspect of picturesque beauty not soon forgotten when once seen. The springs flow from beneath a precipitous bluff out of the rocks, filling a pipe six inches in diameter. The water as it flows has a temperature of 4N° F. The water is a mild alkaline-calcic, with light chalybeate properties. It is useful in acid dyspepsia, chronic constipation, renal congestion, the early stages of Bright 's disease, and in general debility. Galesville is a thrifty village of about 1,000 inhab- itants, and numbers among its attractions telegraph and telephone facilities, electric lights, water-works, a fine water-power, etc. Emma E. Walker. Arcus Senilis. — Gerontoxon (from Greek, rtpcov, old man, and zi£ov, bow, arch); Macula arcuata or macula cornea; Marasmus senilis cornea;; Annulus senilis; German, Greisenbogen; French, Arc senile. Arcus senilis occupies the peripheral portion of the cornea as a light gray arc. The opacity, smooth on the surface, is more pronpunced toward the limbus, bring sharply defined from it by a narrow, trans- parent strip, while the concavity of the arc emerges gradually into the transparent cornea. The opaque arc always appears first above, and gradually ad- vances downward. It always remains broadest above and is at the same time more opaque in this part. Finally, the two arcs unite at the outer and inner side of the cornea to form a closed ring. The opacity is at first of a light gray color, appear- ing like a silver band. At a later period, the opacity a nines a denser and more creamy tint, increasing at the same time in depth and width. Arcus senilis, as the name indicates, is an affection of advancing years, and rarely occurs under fifty years of age except in those infrequent cases in which it seems to occur as an inherited characteristic. Thus, for example, I know of a family in which three male members have all bad the completed arc as early as at the age of thirty- five, and in none of them is there any apparent cachexia. I he condil ion is usually bilateral, although one eye alone may be affected. It occurs more frequently and at an earlier date in men than in women. In warm climates it is developed earlier than in cold latitudes, and it is frequently seen in negroes on the north coast of Africa. A condition resembling very much arcus senilis is found in the young, but is not to be confounded with it. It has been called by Wilde nreus juvenilis, and may be distinguished from the former by the presence of a diaphanous ring between the margin of the eornea and the opacity. Arcus senilis never interferes with vision, although it may extend somewhat into the corneal substance. Occasionally a genuine example of this affection appears to have been noted in children (Hansell). A rare change occurring in the arcus senilis consists in its becoming steadily wider while the cornea in the area of the arcus becomes thin, so that a gutter- shaped depression is formed here, which, yielding to the intraocular pressure becomes ectatic. Pathology. — Arcus senilis is due to an infiltration of a finely granular hyaline substance. It is com- monly stated, even in the more recent text-books, that it is due to a fatty degeneration or infiltration of the cornea; but this has been shown by Fuchs not to be the case, for he says it- is a typical example of physiological, non-inflammatory opacity. He found that the infiltrated material never has any relation to the cells of the corneal tissue, but lies free upon the surface of the connective-tissue fibers. Neither ether nor chloroform has any effect upon it; consequently it cannot be of a fatty character. Fuchs considered it to be a hyaline degeneration of certain fibers. In Fuchs' latest edition (English translation published in 1911), he accepts Takayasa's view, and figures his section of the cornea. Takayasa found very minute drops of fat in the lamella? of the cornea even as far back as Descemet's membrane. This deposition of hyaline masses is also associated with deposits of minute particles of lime on the more superficial layers of the cornea, close to the limbus, and the cause is assumed to be a senile atrophy of the limbus, with involution of a portion of the vascular loops contained therein. Gruber attributes the appearance of these changes in this particular portion of the cornea to the peculiarities of the circulation in the cornea; the peripheral zone being nourished mainly by transudation of nutritive materials from the circumcorneal plexus. At the same time the changes in question are favored by the fact that, with advancing age, the circulation grows less active and consequently the nutrition progresses more feebly. Arcus senilis would, therefore, appear to be a phenomenon that occurs in perfectly healthy people, is due to the decrease of nutrition incident to advanc- ing years, and has no relation to fatty degeneration of the heart, as was formerly supposed. There are no symptoms. The slight disfigurement and the apprehension of future trouble which many, not knowing its character, anticipate, constitute the only sources of annoyance. So far as the patient's fears are concerned, these may easily be allayed; for the condition never interferes with vision. Incisions through the arcus senilis, as in the extraction of cataract, heal as well as those made through the clear parts of the cornea. William Oliver Moore. Area Embryonalis. — The embryonal area, also called germinal disk and embryonic shield, is that part of the blastoderm of meroblastic eggs which gives rise to the body of the embryo, as distinguished from the extraembryonic part, from which the yolk-sac, amnion, and chorion take their origin. In the vertebrate series there are two types of embryonal area; the selachian type, found in the selachian and teleost fishes; and the reptilian type, characteristic of reptiles, birds, and mammals 518 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ari'.i Embryonalla ( Amnio ta). In this article attention will be confined to the latter typo. In an early stage of the amniote egg the embryonal area (Fig. 289) may be distinguished as a circular or oval area covering the animal pule of the egg, and isting of two membranes. The outer membrane is the ectoderm and may be several cells thick; the inner membrane is the endoderm and is usually, for the must pari, a single layer of cells. Fig. 287. — Area Embryonalis of a Chick Incubated Fifteen Hours, View by Transmitted Light. X 14. ao, area opaca; ap, area pellucida; c, anterior crescent; in, mesoderm; p, priniitive streak. (From Duval.) In the bird 's egg, the embryonal area forms the roof of a shallow cavity excavated in the yolk and filled with fluid. This cavity is known as the sub- mittal cavity (Fig. 28S). As a result of the seg- mentation of the ovum, the yolk forming the walls of the subgerminal cavity is provided with nuclei, which also extend some distance along the peripheral Cortion of the floor. The nuclei are not separated v cell walls. The syncytium thus formed is called the periblast. (Lillie 190S, p. 4S.) If at an early stage a blastoderm be removed from a hen's egg and examined by transmitted light 287), it will be seen that the central part is much more transparent than the peripheral zone. The central part is known as the area pellucida, the flattened cells containing little or ao yolk; in the opaque area the endoderma] cells are larger, deeper, often columnar, and filled with yolk granules. The endoderm of the area opaca and the marginal peri- bla i together constitute the germ wall. (Lillie, 1908, 1). 51.) In the area opaca three zones may be distinguished Fig. 289. — Diagrammatic Reconstruction of a Pigeon's Blasto- derm, Thirty-eight Hours after Fertilization. E, endoderm of area pellucida; PA, outer boundary of ana pellucida; SO, subgerminal cavity; 0, region of overgrowth; Y, inner germ-wall; Z, zone of junction; R, mass of cells. X22. (After Patterson.) (Fig. 289); (1) the inner germ wall, a ring of thickened endoderm continuous with the endoderm of the area pellucida; (2) the zone of junction, where the endo- derm merges with the periblast, or rather where the periblast nuclei become surrounded by cell walls and give rise to new cells of the blastoderm; and (3) the margin of overgrowth, where the edge of the blasto- derm, chiefly ectodermal, is continually extending over the surface of the yolk in advance of the expan- sion of the germ-wall. Fig. 288. — I. A Median Longitudinal Section of a Blastoderm of a Pigeon Taken Thirty-eight Hours after Fertilization, or Three Hours before Laying. X 57. II. Enlarged anterior portion of the subgerminal cavity of the section represented in I. X 1.34. III. Enlarged posterior portion of I. X 134. .4, Anterior end; P, posterior end; AC, subgerminal cavity; D, mass of cells at R in Fig. 2S9; E, endoderm; EC, ectoderm; GW, germ wall; L, anterior limit of endoderm; M , yolk masses in subgerminal cavity; 0, zone of overgrowth. (From Patterson.) peripheral part as the area opaca. Examined in situ, the ana pellucida will be found to cover the greater part of the subgerminal cavity, while the area dpaca covers only the edges of the cavity and extends out over the yolk in contact with the marginal periblast. The difference in transparency of the two areas is due to the differences in their endodennal cells. In the pellucid area the endoderm is composed of thin, The first indication of the axis of the future embryo is the appearance of a linear opacity in the area pellucida extending from a little behind the center toward the posterior margin (Figs. 287 and 293). This is the primitive streak. Soon a depression appears along its median line, the primitive groove, bounded on the side by two slight elevations, the primitive folds. Examinations of sections through the priuii- 519 Area Embryonalis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tive streak i Fig. 290 and 292) show that it is produced by proliferation of the ectoderm, which eventually comes into contact with the endoderm and appears to fuse with it. Behind the posterior termination of the primitive groove the primitive streak spreads out gw en \ ec gw 1 Fig. 290. — A, Transverse Section Through the Posterior Part of the Blastoderm of a Chick Incubated About Ten Hours, X21. ii. Median portion of the same, X65. ec, ectoderm; en, endoderm; gw, germ- wall; m, mesoderm; o, zone of overgrowth; ;>, primitive groove; s, subgerminal cavity; y, yolk. (After Duval.) forming the primitive plate. In front of the opposite end of the groove is the anterior termination of the primitive streak in an ectodermal thickening known as the primitive knob, Hensen's knob, or the proto- chordal wedge of Hubrecht (190\S). -I" Fig 291 — Embryonal Area of a Dog's Blastocyst Thirteen to Fifteen Days after Coitus, Showing Primitive streak and Primitive Knob, a and 6, planes of sections in Fig. 292. X 100. (After Bonnet.) From the sides and posterior end of the primitive ik the cells migrate or grow out laterally and posteriorly between the two primary germ-layers. The middle layer thus formed is the mesoderm. The lateral portions of the mesoderm are known as the mesodermal wings, and the posterior parts, with which they are continuous, is the ventral mesoderm of Hubrecht. Soon after the establishment of the primitive streak a new axial structure appears extending forward from the primitive knob. This is the head process, or forward extension of the protochordal wedge of Hubrecht. In a surface view of a hen's blastoderm ■MKS §» — en ■ fc 1 i • Fig. 292. — Sections of the Embryonal Area of a Dog shown in Fig. 291, planes a and b. Upper section through the primitive knob, lower section through the primitive streak, tc, ectoderm; en, endoderm; p, piimitive pit; ps, primitive streak. X 180. (After Bonnet.) it looks very much like the primitive streak, but in sections it is seen to be separate from the overlying ectoderm and to be continuous with that layer only at the primitive knob, from which it appears to be an outgrowth. Below, it comes into contact with the endoderm and fust's firmly with that part of the endo- derm lving in the median line that Hubrecht calls the protochordal plate. The axial cells of the proto- ■ j J ■ Mtiii.. . . . Fig. 293. — Area Embryonalis of a Chick Incubai Hours. X 13. c, anterior crescent; ch, notochord; plate; p, primitive streak. (From Duval.) d Nineteen , medullary chordal wedge and the protochordal plate are destined to become differentiated into the notochord, the first rudiment of the skeleton of the embryo. In the primitive knob a depression appears, the primitive pit (Fig. 292). This goes no further in the chick, but in some other birds and in the reptiles it penetrates the blastoderm, so that there is an opening from the subgerminal cavity to the exterior, called 520 REFERENCE IIAX11ROOK or T1IK MKDICAL SCIENCES Area Embryonalis ,1, nteric canal. In mammals the pit extends M ., lender, horizontal canal into the head proce where at first it ends blindly, and is culled the noto- chordal canal. The cells in the roof of the canal are ined to take part in the development of the noto- n Fio. 294. — Area Embryonalis of a Chick Incubated Twenty Hours. ■ 11. av, area va* ilosa; c, anterior crescent; cA, noto- . , medullary fold; p, primitive streak. (From Duval.) chord. The floor of the canal acquires one or more irregular openings into the underlying yolk-cavity and finally disappears, leaving only the part of the canal that penetrates the knob; this part then becomes the neurenteric canal. "1 L . - -■ 1 Fig. 295 Area Embryonalis of a Chick Incubated Twenty-one Hours. 11 a, head-fold; av, area vasculosa; c, anteri ir ent; ch, notochord; ms, mesodermal somite; n, medullary fold; p. primitive streak; st. sinus terminalis. (From Duval.) The mesoderm continues to spread, not only pos- teriorly and laterally, but also forward along the sides of the head process, with which, in the chick and many other forms, it appears to be continuous. According to some authors all of the mesoderm is de- rived from the primitive streak, while others believe that the head process contributes its share to the anterior portion of the mesodermal wings. In the course of its growth the mesoderm extends across the area pellucida and in ade i he inner zone of the area opaca i Fig. 294). In this portion of the area Fie,. 296.— Embryonal Area from a Dog's Blastocyst Seventeen I laj 9 and Seven and ( (ne-half Hours After the Last Coitus, Show- ing Primitive Streak, Primitive Knob, and Medullary Groove. X 18. (After Bonnet i opaca, which thus becomes three-layered, the first blood-vessels arise, and, fusing, give rise to a capillary net-work, which grows across the area pellucida and enters the embryo. The part of the blastoderm that contains this net-work of blood-vessels is known as the area vasadosa. The first rudiments of the blood vascular system consist of small thin walled vesicles containing" clumps of cells that soon become colored red with hemoglobin. These groups of cells with their envelopes are called blood islands. They lie between the endoderm and the mesoderm, and, after lirsl appearing at the posterior edge oi the mesoderm, spread rapidly round its sides. Because of their equal proximity to two germ-layers, their origin is still a disputed question. The best view, however, appears to regard them with Hubrecht as mesodermal structures of endodermal origin. The rudimentary blood-vessels and blood were regarded by His as constituting a separate tissue, or embryological unit, to which he gave the name, angioblast. The origin ami fate of this layer is discussed more full}' elsewhere (see article Blood-vascular System, Origin of). Finally the area embryonalis is completed by the appearance of the medullar}! jdale. the first rudiment of the nervous system. This is differentiated out of the ectoderm in front of the primitive knob along the median line and for some distance on each side of it. It may also extend backward along the sides of the anterior part of the primitive streak. In time of appearance it is nearly synchronous with the head process. (Fig 295.) In the chick the medullary plate is a flat layer of 521 Area Embryonalis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ectoderm, several cells thick. This merges without any sharp line of demarcation into the surrounding ectoderm. In mammals the plate appears almost from the first as a shallow groove, the medullary amniotic ectoderm and that of the embryonal area. The endoderm is a minute vesicle of flattened epithe- lium enclosing the so-called yolk-cavity. The area embryonalis is represented by the adjoining portions of the ectoderm and endoderm with a very thin layer of rnesenchymatous tissue between. In Peter's ovum the ectoderm of the area embryonalis is composed of high cylindrical cells, and is thus differentiated from the thin amniotic ectoderm. Be- tween the ectoderm and the endoderm there is a layer of mesoderm, which is separated from the ectoderm by a mem- brana prima. This appears in sections as a fine contour. Herzog (1909) has described a human blastocyst that he regards as of about the same age as Peters's ovum, but the men- strual history is unknown. The embry- onal area is distinctly differentiated and is 0.112 mm. in length. It is boat- shaped, rounded anteriorly, and pointed behind, and it is concave, the concavity being toward the amniotic cavity, which is circular in transverse sections. A transverse section through the middle of the embryonal area shows all three germ layers with diagrammatic clearness, but at the extreme anterior end the meso- derm is wanting. The ectoderm of the embryonal area is two or three cells deep, and in the median sagittal plane is an opening that is regarded as possi- bly a neurenteric canal. Rudimentary blood-vessels are observed near the junc- Fig. 297.— Area Embryonalis of a Rabbit of Eleven Days, with the Ectoplacenta ture of yolk-sac and connective stalk. Partly Torn Off. (After Van Beneden and Julin.) pr.a., Pro-amnion; a. a., area The allantois has made its appearance as amniotica; a.v., area vasculosa; a.pl., ectoplacenta; v.t, sinus terminalis. a rather slender, somewhat curved canal of endodermal cells extending into the groove, and in the dog (Fig. 296) (Bonnet, 1901) it is only one cell thick. The appearance in the blastoderm in front of the medullary plate of a crescentic groove, the head fold, (Fig. 295), carries the embryo beyond the scope of the present article. In some animals, of which the mouse is the type, the area embryonalis is covered perma- nently by a specialized part of the trophoblast, known as the ectoplacenta. In adaptation to this condition, the embry- onal ectoderm, instead of form- ing a fiat surface, becomes the lining epithelium of an elon- gated sac (Fig. 298). This sac is covered externally by the embryonal endoderm, and is surrounded by the cavity of the yolk-sac. In the mouse, therefore, the development of the primitive streak and other structures of the area embryo- nalis, is modified by this ex- traordinary condition, which has been called inversion of the germ-layers. (See Blasto- derm.) Descriptions have been pub- lished of a number of human blastocysts in stages showing the area embryonalis. In the youngest of all, the Teacher-Bryce ovum, this area is not sharply marked off from surrounding struc- tures. The embryonal ectoderm is a spherical vesicle composed of cubical cells and enclosing the amniotic ()1) with an embryonal area 1.17 mm. long and 0.6 mm. wide. The primitive streak (Fig' 302) is well developed, 0.5 mm. long. A anterior end is the neurenteric canal and at its Fit . 300. — Transverse Section of Spee's von Herff Ovum, a. amnion; .'. Ferdinand Graf (1889). Beobachtungen an eincr mensch- lichen Keimscheibe mit offenen Medullarrine und Canalis neuren- tericus. Arch. Anat. u. Phys., 18S9. Anat. Abt., p. 159-172. 1906). Neue Beobachtungen iiber sehe fruhe Entwickelungsstufen des menschlichen Eies. I. c, 1896, p. 1-30. Areca. — Areca Nut; Betel Nut. The ripe seed of Areca Catechu L. (Fam. Palmos). The areca palm is a fine large tree, with smooth, graceful stem and a handsome crown of long pinnate leaves. The flowers are monoecious; the fruit is egg-shaped, with a fibrous mesocarp and a hard stone consisting of the seed and adhering eridocarp. This tree is a native of India, the Sunda Islands, and probably of other neighboring parts. It is cultivated there and else- where in the tropics for the sake of its seeds, which have been an article of Asiatic commerce for centu- ries. There is still an enormous consumption of them in China and India, chiefly as a masticatory; for this purpose they are boiled, or used when fresh and soft. They are often chewed with the leaves of the betel pepper and lime. Their introduction into European medicine is rather recent. Areca nuts of our market consist of the kernel of the seed only, the testa being removed with the peri- carp. They are about two centimeters in diameter, and about as long as broad. Their shape is between spherical and conical, with a very blunt rounded point, and a broad, flat, or sometimes depressed base. The surface is of a cinnamon brown or grayish color, and covered with a network of vein-like lines, which radiate irregularly and spirally from the base toward the apex. The albumin is very hard and bone-like, and upon being sawed through presents a marbled surface like that of the nutmeg, caused in the same way, that is, by the infolding of the brown surface layer of the seed (endosperm), which takes place under the reticulated lines above described. The general color of the section is whitish, the lines are brown. The important constituent of areca is its alkaloid, arecoline, which is oily, volatile, miscible with water or alcohol, strongly alkaline, very poisonous, and yields crystalline salts. Its other three alkaloids, arecaine, arecaidine, and guvacine, are not poisonous, and apparently not active. Areca also contains fourteen per cent, of fixed oil, much tannin, and some resin. Although the teniacidal properties of areca reside in the arecoline, which is given to horses for this purpose in doses of 0.03 to 0.06 gram (gr. ss. to i.), this dose acting also as a cathartic, it is too poi- sonous for use in human practice. A solution of one-per-cent. strength is instilled into the human eye as a niyni ic. Powdered areca is frequently given as a teniacide, in doses of ~>ij. to iij. (8.0 to 12.0). It also acts as an astringent, so thai the usual accompaniment of a cathartic must be resorted to. H. II. RXFSBT. Aretaeus. — It is uncertain at exactly what period of time Aretaeus flourished, but the consensus of opinion favors the belief that he lived from the middle of the first century of our era to about the year 138. It is also not known surely in what part of the ancient world he practised his art, although it is generally believed that the scene of his labors was located in Italy (but not in Rome). His birthplace was in Cappadocia, in Asia Minor. Notwithstanding the fact that all the historical documents relating to Aretreus have long since perished, we still possess to-day, in almost their entire completeness, the monuments of his remarkable genius. His great treatise on the causes, symptoms, and treatment of acute and chronic diseases, published in Latin in Venice in 1552, is a model of carefulness and accuracy in the descriptions of disease which it contains and in the correctness of the diagnoses made. The methods of treatment advocated by Aretauis would be pro- nounced to-day unnecessarily energetic. A. H. B. Argas. — A genus of ticks which contains species which sometimes attack man, though they are usually found on birds. A. americanus, or A. persieus, is a pest in some parts of this country; this species is said to be able to live four years without food. See Arachnida. A. S. P. Argasinae. — A subfamily of the ticks, Ixodidce, which have the rostrum below the anterior margin of the body. These arachnids are parasitic on warm- blooded vertebrates, particularly birds. Argas is a genus sometimes found on man. See Arachnida. A. S. P. Argemone. — Mexican Poppy. Of these plants the most important thing that can be said is that they are eminently worthy of careful investigation. They were formerly regarded as constituting but a single species, but are now known to represent several. Of these, it is not certainly known which supplied the material upon which previous studies were based, so that we are able to speak only of the group in gen- eral. They are very widely distributed through the tropical and warm parts of America, as well as widely introduced into Africa and tropical Asia. The plants are of striking appearance, two or three feet high, with large, broad, glaucous, prickly-toothed leaves, large poppy-like white or yellow flowers and prickly capsules. On being wounded, they exude a thick yellow juice. They grow in great abundance in waste places and over dry sterile soil. They have been used medicinally in the form of an extract of the whole plant, of the expressed juice, of the si and of the oil expressed from the seeds. The juice has been ignorantly used in venereal diseases, and in- stilled into the eye for conjunctivitis. This juice contains in very small amount an alkaloid which has been claimed to be morphine. The fixed oil of the seeds, yielded to the extent of about thirty-six per cent., has received the most attention. It has been clearly shown to be mildly cathartic, without bad effect, in doses of four to five grams, and to form a tasteless and not unpleasant substitute for castor oil. Taken in larger doses it and the seeds are cinet- ico-cathartic, with the symptoms of local irritation. H. H. Rusby. Argentum. — Silver, a metal of lustrous white color. It is one of the elements, symbol Ag, atomic weight 107.88. Metallic silver is used in medicine only in the shape of fine wireasasuture material, and occasionally in the form of a thin leaf in surgical dressings. General Medicinal Properties of Compoum>s of Silver. — In medicinal dosage the most important effect that follows persistent internal medication with silver is the tendency to a bluish-black discolor- 524 REFERENCE HANDBOOK OK THE MEDICAL SOIEM CS ArRrnium alion of ( lie skin and mucous membranes. (See Argy- ria ) This staining shows first cm the mucous mem- hrancs, so tliat liy inspection of the inner surfaces of I he lips anil of the fanees, during a course of medical ion by silver, and by stoppage of the medicine upon the first beginning of a bluish discoloration of those parts, no serious risk of staining of the skin need he incurred. As a rule, efficient dosage with silver can be maintained for from one to three months before coloration begins. In overdosage silver is a constitutional poison, im- pairing nutrition generally, and deranging the nervous System particularly. Therapeutically, impregnation of the system with silver tends to oppose feebly the onward march of certain diseases of the nervous tern, such as epilepsy and tabes dorsalis. Bui in the more intractable of these diseases, such a> i abes, t he influence is so slight as to be of no value — if, indeed, it exists at all — and in epilepsy other remedies are far more potent. The use of silver for con- stitutional effect is, therefore, in modern practice quite abandoned. Locally, the effects of silver compounds differ with the individual preparations according to their solu- bility, and will be described in connection with the several compounds themselves. The Compounds of Silver Used in Medicine. — These comprise the oxide and nitrate. The cyanide is also official in the United States Pharmacopoeia, but for pharmaceutical purpose only. Argenti Oxidum. — Silver oxide, Ag,0, is a heavy, dark brownish-black powder, odorless, but of a metallic taste. It is liable to undergo reduction upon exposure to light. It is very slightly soluble in water and is insoluble in alcohol. It should be kept in dark amber-colored bottles, protected from the light. This oxide readily yields its oxygen in pres- ence of oxidizable matter, and hence should not be triturated with any such material. It dissolves in water of ammonia. From its comparative insolu- bility this compound has little local effect, but when swallowed, probably through chemical conversion, it. is capable of absorption, and exerts the constitutional effects of silver such as they are. In such operation the oxide is thought to be less prone to discolor the skin than the nitrate, but it is certainly not wholly innocent of this tendency. Upon the stomach and bowels silver oxide has quite a marked potency to allay irritability, tending to quell vomiting, even in such complaints as ulcer and cancer of the stomach, and to control diarrhea when arising as a reflex of nervous irritation. The principal employment of the medicine is iu such disorders of the digestive apparatus. The average dose is about gr. j. (0.06), best given in powder or capsule. The pill form is bad, because of the deoxidation of the compound by the organic matter of the excipient, which reaction may even be attended by explosion. Gum arabic is recom- mended as the least objectionable excipient. Argenti Nitras. — Silver nitrate, AgN0 3 . This title in the U. S. P. signifies the salt in crystals. These crystals are smafl, transparent rhombs, originally colorless, but gradually becoming grayish-black on exposure to light and air. They are odorless, but have a strong metallic taste. They dissolve freely in water, in twenty-four parts of cold alcohol, and in five parts of boiling alcohol. When heated to about 200° C (392° F.), the crystals fuse to a faintly yellow liquid, which, on cooling, congeals to a purely white, crystalline mass. Silver nitrate should be kept in dark amber-colored vials protected from the light. These crystals constitute the purest form of the nitrate, and are used for internal administration or for the making of solutions. _ Argenti Nitras Fusus. — Moulded silver nitrate, fused nitrate of silver. Lunar caustic. The crystals are melted by heat, and the fused sa.t poured into moulds where it sets on cooling. But inasmuch as the pure nitrate is, when fused, inconveniently brittle, the Pharmacopoeia provides for a trifling admixture of silver chloride, which is a tough compound. To this end about four per cent, of hydrochloric acid is added to the melted crystals, whereby a small portion of the nitrate is converted into chloride. Reaction ha\ ing ceased, the mixed mass is ready for moulding. Lunar caustic is cast in narrow cylindrical sticks which are hard, brittle, and, when freshly made, white i u color. As commonly found, however, I hey are gray, or even blackish, through chemical reaction with mat- ters present in the atmosphere. Fused nitrate of silver should be used only for its legitimate purpose, that of external application. The sticks should be kept, protected from the light. Argt nli \ itras Mitigatus. — .Mitigated silver nitrate. Silver nitrate and potassium nitrate, the latter in double the quantity of the former, are melted to- gether by heat and the fused mass moulded into sticks like those I'f the simple moulded silver nitrate. The sticks of the mitigated nitrate resemble those of the pure nitrate except that they are granular rather than fibrous in texture. They should be kept protected from the light. The sticks dissolve freely in water and possess the same properties as the undiluted lunar caustic, only in milder degree. They are used only for local application. Silver nitrate differs from the oxide in the essential particular of free solubility, on which property depend the most valuable medicinal virtues of the salt. The most important reactions of the nitrate are that its solutions are precipitated by soluble chlorides to form the very insoluble salt, silver chloride. This reaction is one of the most delicate in chemistry, and since traces of chlorides are present in almost all natural waters, the use of distilled water is necessary for solutions of siver nitrate, if a clear, bright solution be desired. Silver nitrate also reacts on organic matter generally, suffering decomposition, and form- ing with the organic substance compounds insoluble and acquiring a rusty brownish-black color under the action of light. Hence sticks of lunar caustic grow gray and black on the surface by keeping, by reaction with the organic dust of the atmosphere, and solutions of silver nitrate deposit a fine black sedi- ment and stain textile fabrics and skin. The stain on the skin, if recent, can be removed fairly well by rubbing with a moistened lump of potassium cyanide, and washing — always remembering the very irritant and poisonous character of such cyanide. But if the stain be old, and fixed by exposure to sunlight, the cyanide fails, and the following means may be re- sorted to: Moisten the stains, drop on them a little tincture of iodine, and then wash in a 6 per cent, solution of sodium hyposulphite. Or, very efficient, mix in a saucer a few bits of iodine with a little water of ammonia; rub the stains quickly with the resulting preparation, and immediately wash both skin and saucer wdiile they are still wet. This latter precau- tion is necessary, since the compound of iodine and nitrogen spontaneously explodes upon slight agitation when dry. Other reactions of silver nitrate are its precipitation by sulphuric, phosphoric, hydrochloric, and tartaric acids and their salts; by the alkalies and their carbonates, lime water, and the vegetable astringents, and arsenical and albuminous solutions. Silver nitrate is an irritant astringent, with also the peculiar specific effects of silver compounds already detailed, viz., the allaying of gastric irritability, and the induction of certain constitutional control over nervous disease. The local effects are the more important and are as follows: The salt readily com- bines with albumin to make an insoluble compound, the albuminate of silver; hence, when in strong solu- tion or in solid stick, its application to the surface of a mucous membrane or of granulation tissue produces a white streak of cauterization, which, by the insolu- bility of the compound formed, limits the action of 525 Argentum REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the caustic to the production of such shallow slough. Concentrated applications to the skin speedily blacken the epidermis, and, more slowly, raise a blister. In solutions less than ten per cent, in strength the salt is hardly caustic, but acts only as an irritant astrin- gent. When swallowed, quite small doses act locally like the oxide, while large dosesproduce irritant poison- ing. Therapeutically, local applications of silver ni- trate judiciously made have a marked tendency to promote absorption in such tissues as are capable of undergoing this process; to induce healing; to limit and abate the catarrhal process; to destroy skin para- sites, though not very searchingly; and to neutralize the virulence of specifically noxious pus. The medicinal uses of silver nitrate are such as may be deduced from the foregoing. Internally the medi- cine may be given, for constitutional or local effect, in doses of about gr. £ (0.01) in pill or solution. In neither way of giving does the salt probably reach the stomach as nitrate; for, if in solution, a medicinal dose must almost certainly be decomposed in the swallowing, and, if in pill, be acted on similarly by the necessary organic matter of the excipient. To obviate this effect as far as possible in the case of pills, it is advised that bread-crumb be particularly avoided as an excipient, beeause of its containing a soluble chloride (common salt) as well as organic matter, and that some vegetable extract, or a dry powder made sticky by a minimum of gum, be selected. In any case the crystallized silver salt should alone be prescribed. Externally, silver nitrate may be used as a caustic, but only where a superficial effect is wanted, as for the destruction of the lining membrane of a cyst. The fused stick is in such cases used, its moistened surface being swept over the sur- face to be destroyed. More common is the applica- tion to promote absorption, as in case of exuberant granulation tissue or trachoma bodies; to determine healing, as in unhealthy ulcers; or to shorten and abate the course of a catarrh. For such purposes various strengths of the nitrate are used, from appli- cation of the pure or mitigated sticks of lunar caustic to that of solutions of not more than the one-fifth of one per cent, strength. To determine absorption the stronger applications are necessary, to control catarrhs the weaker, but in all cases care should be taken not to overdo the matter, and, by too strong or too fre- quent application actually to interfere through excess of irritation with healing or with resolution. In the case of catarrhs, moreover, the remedy should not be used at all until the second stage of the process is reached, as betokened by the establishment of the catarrhal secretion and abatement of the initial pain or sensitiveness. Then, too, the strength of the application should be adjusted to the different degrees of sensibility of the different mucous membranes; for while the comparatively insensitive membranes, such as those of the fauces or vagina, may take a five- per-cent. solution, or even stronger, hardly more than the one-tenth of this strength can be applied without undue irritation to the nasal passages or to the male urethra. ^Tien a very brief action is wanted, the application of silver may be followed immediately by one of a solution of common salt, which salt immedi- ately precipitates all excess of nitrate as the insoluble and therefore inert compound silver chloride. Argenti cyanidum, silver cyanide, AgCN, is an insoluble white powder not used in medicine, and official only for the making by the pharmacist of diluted hydrocyanic acid. Besides the foregoing, a number of unofficial preparations of silver deserve brief notice. Argyrol. — Silver vitelline. A salt solution of vitelline, a derived protein obtained from gliadin, is precipitated by silver oxide. Such precipitate — silver vitelline — properly dried, appears as a dark- brown powder. The substance contains from twenty to twenty-five per cent, of silver, and is remarkable for being extremely soluble in water, while at the same time it does not precipitate albumin or sodium chloride, and is wholly unirritating. Its solution also penetrates albuminoid tissues very readily and thoroughly. Silver vitelline thus pos- sesses all the desiderata for an ideal silver preparation, and has been used with great success as a local appli- cation in inflammations of the mucous membrane of the eye, ear, nose, vagina, urethra, and bladder. It is employed in aqueous solution ranging in strength from one-tenth of one per cent, to twenty-five per cent, and upward, according to the character and sensitiveness of the part. Even a ten per cent, solution applied as an injection in acute gonorrhea produced no irritation (Christian). Collargol. — Colloidal silver. This is a bluish-green substance obtained by precipitating with silver nitrate a mixed solution of ferrous sulphate and sodium citrate. Collargol contains about eighty-five per cent, of silver, dissolves in twenty-five parts of water forming a dark reddish-brown solution, and is easily decomposed. Its aqueous solution, on standing, deposits a small sediment of insoluble silver. Collargol introduced into the general circulation is said to exercise curative power over the conditions of general septic infection, whether by action on the microorganisms themselves or on their toxins is not clear. At the same time the remedy is non-poison- ous and, being rapidly eliminated after absorption, does not produce argyria. The only untoward effect observed has been a slight chill and rise of tempera- ture, but even this is not seen if (using by intraven- ous injection) care is taken that the solution be free from sediment. Collargol may be administered by inunction or by intravenous injection. For the latter method a carefully prepared, freshly made solution in distilled water is to be used, of a strength of one-half to one per cent. If a sediment forms, the supernatant liquor must be decanted. Of such a solution from half a fluidram to five fluidrams may be injected directly into some superficial vein once or twice daily, or every two or three days. The more common method of administration, however, is by inunction. For this purpose a fifteen per cent, ointment is used, of which the quantity of from thirty to forty-five grains is rubbed thoroughly into the skin of the inner side of the arms or thighs, or of the back, from one to three times daily. Collargol ointment decom- poses readily and should not be exposed to the air. An ointment should not be used that shows white crystals on the surface, or that fails to color the skin black on inunction. An ointment, "Unguentum Crede" contains fifteen per cent, of collargol in a mix- ture of lard, wax, and benzoic ether. Urol. — Silver citrate, Ag,C H 5 O 7 . This compound is a fine dry powder without taste or smell, very slightly soluble in water. Its solution is immediately decomposed by organic matter. Like silver vitelline, it is non-irritant and penetrating, and has been pro- posed as a surgical disinfectant and for injection in gonorrhea and cystitis. The strength of solution ranges from 1 to 4,000 to 1 to 10,000. Actol. — Silver lactate. AgC 3 H 5 3 . This compound is a white powder, without taste or smell, and soluble in from fifteen to twenty parts of water. It is a powerful germicide, and penetrates tissues, although decomposed by contact with the same. It is used as a surgical antiseptic, and strong, even saturated solu- tions may be applied to infected parts. Ordinary strengths are from 1 to 100, to 1 to 2,000 parts of water. Argentamin. — This name is given to a solution of silver nitrate (10 parts) in a ten-per-ccnt. aqueous solution Of the organic base ethylendiamine. It is a clear fluid, strongly alkaline, and is devised to give a non-poisonous and unirritating antiseptic so- lution which shall not precipitate albumin. It is .v_v, REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Areyrla used in the anterior urethra in 0.25 to 1 per cent, solution; in the posterior urethra in from i to 4 per solution; and in the eye in ."> per cent, solution. Argonin. —Casein silver. This name is given to a body obtained by precipitating with alcohol a mixed tion of silver nitrate and a sodium compound of casein. Argonin is a white powder, neutral in reac- tion; insoluble in cold water, hut readily soluble in u or albuminous water. Solutions must be kept away from exposure to light. It has been used in g >rrhea in solutions of from 1 to 7 parts in 1,000 Of water. Protargol. — This name is given to a silver albumose containing eight per cent, of silver. It is a yellow der, freely soluble in water; unaffected by heat. albumin, or sodium chloride in weak solution, and wholly unirritating. It may be used with great freedom as a local application, being employed in .solutions varying in strength from 0.25 to lit per cent. AVbargin. -Gelatosilver. A compound of silver nitrate with gelatose, containing about fourteen per cent, of silver. It is used as a substitute for silver nitrate. —Colloidal silver oxide. L'sed as a substitute for the ordinary compounds of silver in treatment of inflamed mucous membranes, and as an intestinal antiseptic; in diseases of the eye and of genitourinary tract, it is used in 5 to 25 per cent. colloidal suspension; on other mucous membranes in 10 to 50 per cent, colloidal suspension. Hcgoimn, contains about seven per cent, of organ- ically combined silver and is used as a substitute for silver nitrate. Ichthargan. — Argenti ichthyol sulphonas, silver ich- ilate, said to contain thirty per cent, of metallic silver, and fifteen per cent, of sulphur in organic combination. It is chiefly used in gonorrhea in 0.04- tii 0.2 per cent, solution; in posterior urethritis in 3 percent, solution; and in trachoma in 0.5 to 3 per cent, solution. tfovargan. — Argenti proteinas, silver proteinate, contains ten per cent, of silver. It is said to be use- ful in gonorrhea, especially in the first stage. R. J. E. Scott. Argyria. — This is a term (also argyrism, argyrosis, argyriasis) applied to the discoloration of the skin and certain other tissues of the body resulting from the long-continued medicinal use of soluble silver salts, and caused by the deposit in the affected tissues of metallic silver, or some of its lower compounds, in a state of minute subdivision. The same condition may be produced by the absorption of soluble silver com- pounds from mucous membranes or wound-surfaces. or from the entrance of silver-dust through the skin or respiratory tract. Clinically the condition is characterized by a slaty or grayish-brown, or in the most severe cases, by a bluish-gray discoloration of the skin (Moor's skin), conjunctiva?, and visible mucous membranes. When caused by the internal administration of silver the first signs of the pigmentation appear in the form of a blue or violet line on the gums, resembling the lead line but usually more violet in color. The internal organs, with the exception of the central nervous sy.-tem, suffer a similar pigmentation. The discolor- ation of the skin appears to vary in different regions, being less intense where the horny layer is thick, as in the palms of the hands and soles of the feet; and of greater intensity where the horny layer is thin. The pigmentation first appears in those portions of the skin exposed to light. The hair and nails are not affected, but the bed of the latter is usually deeply pigmented. Scars formed before or during the period when the silver was taken are pigmented, but those formed after the cessation of its use remain white. The apparent intensity of the pigmentation also varies with the tempera t ur.' ,.i the surface of the body, being mosl marked in the cold, and greatly decreased when the skin is warm and flushed, The pigmentation increases as long as the internal use. of the silver salt is kepi up and for some time after its use is stopped. Its degree and extent are in direct proportion to the amount used and the period of time through which it- administration is extended. It is essentially a chronic process. The n coloration never disappears, and il is doubtful if the silver deposit is ever removed from the body, though it has been claimed in a number of instances that after the lapse of years a decrease of the color has taken place. (See author'-, case mentioned below.) The condition has been known since the alchemistic period when the internal use of silver salts was very popular, and descriptions which undoubtedly refer to argyria exist in the literature of that time. The first i e mentioned in medical literature is the one ob- served by Schwediauer and reported by Fourcroy in 1791. In the early part of the nineteenth century numerous cases were described, and the number of these increased greatly about the middle of the cen- tury when the use of silver nitrate in epilepsy and tabe- reached it- greatest popularity. At that ti a generation of individuals affected with argyria may be said to have arisen, and frequent examples of the condition came to the postmortem tables of the great European hospitals. That generation has now practically disappeared, and cases of general argyria resulting from long-continued use of silver salts have been of very rare occurrence in the last gen- eral ion. In recent years there has been apparently an increase of cases of argyria as the result of the careless use of the newer silver preparations, particularly in geni to-urinary, ophthalmic, and otolaryngological practice. The present cases of argyria are for the greater part localized discolorations resulting from local medicinal applications of silver nitrate, or from absorption through the skin or respiratory tract of silver dust, as in the case of workmen who file, grind, or polish the metal. Three forms of argyria may be distinguished clinically: argyria universalis, argyria localis circa mscripta, argyria local is dissi m inala. Argyria Universalis. — The condition of universal pigmentation of the skin and mucous membranes is usually caused by the long-continued internal use of silver nitrate but may be due to long-continued occupational contact with silver, or to prolonged local use. The discoloration develops independently of any preexisting condition of the skin or body tissues, and its intensity is in proportion to the amount of silver absorbed and the period of time covered by its administration. As a rule the pigmentation ap- pears several months after the use of the silver is be- gun, and develops slowdy. As the discoloration is usually not observed until it has reached a certain degree of intensity, it is impossible to speak with certainty of the exact course of the pigment deposit. It has been claimed that a blue or violet line on the gums is the earliest symptom, but this does not oc- cur in all cases. When the argyria is the result of the internal use of silver the blue line on the gums is almost always present and is an important diagnostic sign. As it usually appears before the pigmentation of the skin has developed it should be regarded as an indication for stopping the use of silver. The degree and extent of the pigmentation of the skin vary in different cases: the face, thorax, and abdomen may show it earliest and to the greatest degree while the extremities may remain unaffected. The pigmenta- tion of the skin appears in patches, first over areas exposed to the light; the patches become con- fluent until ultimately the entire surface may be- come pigmented. The discoloration usually increases for some time after the use of the silver has been discontinued owing to the presence of unreduced silver still in the body. The mucous membranes 527 Areyrla REFERENCE HANDBOOK OF THE MEDICAL SCIENCES may show no discoloration in intense argyria of the skiii; while on the other hand a marked degree of pigmentation may exist in the internal organs without any great change in the skin. A metallic odor of the breath accompanied by a stomatitis with or without salivation has been described, but the occurrence of these symptoms is very rare or doubtful. There are no symptoms coincident with or following the con- dition that can be said to be the direct result of the deposit of the pigment. The total amount of silver nitrate which must be taken in order to produce a well-marked case of argyria varies greatly, the lowest limit being placed at live to thirty grams. The administration of the metal must be extended through a considerable period of time. Large doses given within short periods pro- duce symptoms of poisoning without the deposit of pigment, while minute doses administered for many months or years produce the most intense discolora- tion. Slight degrees of argyria have been produced by the administration of two grams only (thirty grains). Lionville reported a case in which the total amount of silver nitrate used was only seven grams, but there resulted an intense argyria of the internal organs, the skin over the abdomen alone being slightly discolored. The same writer also claimed to have seen in another case the appearance of the blue line on the gums after the use of thirty pills each containing 0.01 gram of silver nitrate. The skin in this case was not affected. It is, of course, evident that it is the amount of silver absorbed and not the amount taken into the body that influences the degree and extent of pigmentation. With the minute doses of silver nitrate now given and the relatively short periods of administration there is but little danger of the production of argyria; but if the salt is given for any considerable period, the possibility of its occurrence must always be borne in mind and the patient duly informed. A general argyria may also be produced by the local absorption of silver nitrate, as in the long-con- tinued use of applications of the salt in affections of the throat, eye, and urethra. It may also be caused by the long-continued use of hair-dyes containing silver preparations. Lavage of the stomach and large intestine with dilute solutions, when continued for long periods of time, may also lead to general pigmentation. These cases are very rare. Neu- mann observed a case in which after twelve lavages of the stomach with a solution of 1.45 gram of silver nitrate to ninety of water, an intense argyria of the skin of the face, head, neck, thorax, and back was produced. The skin of the extremities was but slightly discolored, and the mucous mem- branes remained normal. In a case observed by the writer the daily irrigation of the colon with a one-per-cent. solution of silver nitrate led in eighteen months to a very marked grayish-brown discoloration of the entire skin, which was most in- tense over the face and extremities. The patient was a lad of fourteen years, suffering from a chronic ulcerative colitis following measles. At the beginning of the treatment there was present a severe grade of anemia with very marked pallor of the skin, the con- dition having persisted for about two years. There were also very severe nutritional disturbances witli stunting of growth and delayed puberty. After six months he had so improved that he was allowed to go home. At this time no discoloration of the skin was noticeable. The treatment was continued during his stay at home, and when he returned three months later the pigmentation of the skin was the first thing noted, although neither the patient nor his friends had observed it. The visible mucous membranes, especi- iilly those of the anus and rectum, were also discolored, but no line could be seen upon the gums. The treat- ment was continued for about nine months longer. During this time the discoloration of the skin increased. He was then discharged as cured. Six years after, he had become very stout, having matured rapidly. The pigmentation while still present had so decreased in intensity that the patient declared that it had entirely disappeared. It is probable that the total amount of silver in his body had not decreased, but that the increase of tissues made it less prominent. Continual exposure to atmosphere laden with silver dust, as in the case of silver grinders and polishers, may lead to a general argyria through absorption from the lungs (see below). There are no other pathological changes associated with general argyria that can in any way be said to be secondary to it. Edema of the skin and degenera- tive changes in the kidneys have been thought to be caused by the deposit of the pigment, but there is no definite evidence to this effect. Chronic interstitial changes in the kidneys, liver, and lungs, associated with arteriosclerosis are believed by some writers to be due to the deposit of silver in these tissues; but the etiological relationship of the silver deposit to those changes has not been definitely shown. Large or frequently repeated doses of silver nitrate may lead to a severe gastritis or even to ulceration of the stomach. Death may result from very large amounts, as in a case reported by Scattergood of a child whose death was caused by the accidential swallowing of a portion of a stick of the nitrate which had been used for painting the throat. Argyria Localis Circumscripta, — The local absorp- tion of silver may result from the continued use of nitrate of silver applications in solution or in the solid stick to mucous membranes or to a wound surface. The single application of the salt leads usually to a precipitate, which is cast off with the superficial slough; but after repeated applications the salt pene- trates more deeply into the subepithelial tissues, where it is chemically changed and precipitated in the form of minute black granules, which, according to their number, lead to a greater or less pigmentation. The discoloration is confined to the seat of application and is as permanent as that of general argyria. Such local pigmentations may occur in the conjunctiva", urethra, throat, gums, tongue, etc. In very rare cases the local condition has been followed by general arg3 r ria. This is most likely to occur in the treat- ment of chronic affections of the mouth and throat, where some of the silver application may be swallowed and absorbed through the stomach. Argyria Localis Disseminata. — In workmen who are engaged in cutting or polishing silver there may appear in the exposed portions of the body, must frequently in the hands and arms, grayish or bluish spots. These may also appear in the face. The spots are pale in the beginning, but gradually increase in intensity and remain unchanged throughout the life of the individual. The pigmentation develops from small particles of silver which either penetrate or are rubbed into the skin. The condition is said to be not so frequent in silver polishers as in workmen who cut or grind the metal. Long-continued expo- sure to an atmosphere laden with silver dust may lead to absorption of the metal through the respira- tory tract and to a general argyria. Such an occur- rence can be explained only by the assumption that the silver particles taken up by the lung are dissolved, and passing into the general circulation are precipi- tated in other parts of the body in the shape of tine black granules. As a support to this view is the fact that silver cannulas, when kept in tracheotomy wounds for long periods of time, show signs of gradual dissolution. Silver wire or plates remaining in the tissues for a long period of time may become disin- tegrated and the local lymph nodes show a heavy deposit of black granules. In the case of a mattress of silver wire retained for twenty years at the site of a hernial operation the writer has seen extensive argyrosis of the regional lymph nodes, the deposit of 528 REFERENCE BAND-BOOK OF THE MEDICAL SCIENCES Argyria the pigment following the endothelium of the lymph- sinuses. Microscopical Appearances.— In general argyria the pigment appears microscopically as very fine blacl granules which are deposited in the connective-tissue stroma near the walls of the capillaries; and maj 1" id in the ill 'i'n lis, mucosa of the mouth, larym tine, kidney, intima of the larger vessels, adven- ,; the mailer ones, mucous glands, peritoneum, icles, bone marrow, liver, spleen, lymph glands, , horoid plexus. The epithelial structures, brain, •Is, muscle fibers, cartilage, bone, hair, nails are not affected. In early stages the leuco- are said I" contain silver-granules, being the i : lis to 'how them. In the .-~ k i ! i the deposit of the pigment is most marked in the stroma of the papillse just beneath the .■ind around the glands. Toward the subcutane tissues the pigmentation decreases in intensity. In the intestine the basement membrane of the mucosa, the connective tissue of tl"' muco a a submucosa, together with the Iymphadenoid struc- how the pigmentation in the greatest degree. In the kidneys the deposit is greater in the glomeruli, especially about the afferent vessels, and occurs to a much less degree in the intertubular connective ■sss.^f^^*' Fh:. 304. — Silver Deposits in the Tunicie Propria? and in the Connective Tissue of the Renal Papillie, in a Case of General Argyriasis. X230. (Aschoff.) tissue. In the liver the pigment is found in the con- nective tissue about the blood-vessels and bile ducts and in the intima of the larger branches of the hepatic veins. Of the other organs, the mesenteric glands, the spleen, choroid plexus, and the testicles show the greatest intensity of pigmentation. The microscopical sections of the spots found in the skin of silver workers present a somewhat different appearance from that of general argyria. The process is analogous to that of tattooing: the small particles of silver which have been rubbed into the skin become surrounded by a connective-tissue cap- As a rule the silver granules are larger than those found in general argyria. In recent cases silver particles may be found in the epithelium, but the epidermis is never involved in argyria due to the internal use of silver. In the neighborhood of the larger particles smaller granules are found scattered throughout the connective tissue, and the elastic tissue of the papilla? and corium is colored brown or black by a very fine precipitate of silver granules similar to that found in general argyria. As in the latter condition, these granules are most abundant just underneath the rete. Fig. 273 shows a section taken from such a silver spot. The elastic tissue network of the papillse and corium i ontains through- out a fine precipitate of silver granules, while coa granules are seen at the periphery of the papillse and t;ii tered through the coi ium. With the exception of the connective < found in silver spots the pre i nci ol thepigmenl gi ules dors not seem to lead to any ei lat patho- logical change. 1 1 has been claimed i hal inter nephritis has followed the deposit of the pigment in the kidney-, but it is much more probable that the two processes were coincident, or wholly unrelated. The problems of thepathogi irgyria remain he present day unsettled. Animal experiments have aided but little in the solution of the que tion, as the artificial argyria produced in animals differs very greatly in its localization and intensitj from the argyria of the human body. Cone, ruing the patho- genesis of the latter various views are held. The olilest of ll i the one introduced by Kramer and supported by Frommann, which holds that the silver nil rate taken into the body is changed by the stomach and intestinal juices into a soluble silver albuminate, which is absorbed from the intestines into the circula- tion and is ultimately passed with the lymph through the walls of the blood-vessels into the tissues, where it is precipitated in the form of fine granules. Opposed to this view is the theory supported by Virchow and Riemer that the silver nitrate is reduced in the intestinal tract and taken up from the latter place in the shape of line granules, partly through the lymph and partly through the blood, into the general circulation, where by metastasis these are deposited in various parts of the body. Jacobi showed that the reduced particles of silver cannot penetrate the epi- thelium of the intestine, and further proved experi- mentally that the greater part of the silver nitrate taken into the body is not reduced in the intestine, but is changed to silver chloride and albuminate, and absorbed as such, the reduction taking place in the tissues. Loew held that the reduction of the silver held in solution in the circulating blood is the result, of the action of living cell-protoplasm, most probably that of the endothelium. On the other hand, Robert holds that the reduction takes place only in certain organs — the liver, kidneys, papillse of skin, and intestinal wall — and that the reduced silver is carried elsewhere by leucocytes, for the greater part to the spleen, lymph glands, and bone marrow, where it is ultimately deposited in the connective tissue. Through "the agency of the wandering cells containing silver granules a part of the silver may be removed from the body. The reduction in the wall of the intestine he holds to be clue to the absorption by the intestinal wall of certain gases, hydrogen and hydro- gen sulphide, which are formed in the intestinal tract by the growth of anaerobic germs, the hydrogen leading to a reduction of the silver, and the hydrogen sulphide to the formation of a silver albuminate sulphide. The reduction of the silver in the papillse of the skin Robert holds to be due to or associated with the process of cornification, which he regards as a reduction process. He explains the fact that argyria in human skin is of so much more constant occurrence than in the skin of animals by the assump- tion that the process of cornification takes place to a much greater degree in human skin. This theory, however, does not receive the support of the actual facts. In the light of our present knowledge the most reasonable hypothesis is that the silver is absorbed from the intestine into the general circulation in the form of a soluble albuminate which is taken out of the blood and reduced by the protoplasm of the endothe- Vol. I. 34 529 Argyrla REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Hal or perithelial cells, and secreted by these cells into the neighboring connective tissue, where it may remain or be further transported by means of wander- ing cells. The deposit of the silver in certain parts of°the bodv cannot be explained by the theory of simple metastasis, and as it has been established beyond doubt that the endothelium in different parts of the body has a selective action, it seems to the writer that the best hypothesis for the explanation of the pathogenesis of argyria is the theory of endo- thelial-cell activity. In surfaces exposed to light reduction may take place as a result of photochemical action, but in the internal organs it must be the result of cell activity. The chemical nature of the fine silver granules in the tissues has not as yet been definitely determined. According to Kobert, the pigment is a loosely held organic compound of silver and presents the following reactions: The granules are insoluble in acetic and dilute mineral acids, fixed alkalies, and ammonia; they lose their black color but do not vanish in strong nitric acid and in moderately strong solutions of potassium cyanide; the black color may be restored by means of hydrogen sulphide. Substances which decolorize the organic pigments have no effect upon the silver granules. If a piece of tissue heavily pigmented with silver is warmed with nitric acid until it loses its color and the acid then filtered off, the filtrate will contain no silver, the metal remaining in the decolorized tissue. Other investigators hold that the pigment is metallic silver or a low oxide (AgO, or AgOJ. The amount of silver deposited in the tissues is very small compared to the amount taken into the body. Experimental analyses of tissues showing a high degree of argyria have yielded only minute quantities of silver. Frommann obtained from 760 grams of liver which had been preserved in alcohol only 0.009 gram of silver chloride, equalling 0.0068 gram of metallic silver. Versmanns found the same amount of metallic silver in 14.1 grams of dried liver, and in 8.6 grams of dried kidney 0.053 gram of the metal. Symptoms. — Pigmentation is the essential symp- tom. Gastric ulcer, chronic nephritis, neuritis, headache, loss of memory and mental depression have been associated with the condition. The relation is not clear. In the case of mental depression and melancholia the psychical effects of the disfigure- ment may be responsible. Diagnosis. — The discoloration of the skin may be mistaken for cyanosis or for the pigmentation of Addison's disease. The blue line on the gums may be confused with the lead line. If the history is not clear, small bits of the skin or gum should be excised and tested. On treating with potassium cyanide or concentrated nitric acid the pigment granules dis- appear, but reappear upon the addition of ammonium sulphide. Treatment. — Since the silver pigment is deposited in the connective tissue outside of the vessels, its com- plete removal during the life of the affected individual is very improbable. Through the agency of wander- ing cells a very slow removal may take place, but it is doubtful if in well-marked cases this leads to any noticeable decrease in the degree of pigmentation. Cases of recovery have been reported, but they are doubtful. Rogers affirms that blistering will lighten the color very much, and Eichmann claims to have produced a cure by means of potash baths. Yandell has reported two cases in which large doses of potas- sium ioditle were given in connection with mercurial vapor baths for several months in the treatment of syphilis with complete cure of the existing argyria, the pigmentation fading very gradually. In spite of these reported cures the great majority of cases arc unaffected by treatment, and the affected individual canies his pigmentation to the end of his life. In ca es similar to the one reported by the writer in which the argyria is produced at an early period of life before puberty, the later increase of tissues may lead to an apparent decrease in the intensity of the pigmentation. The prophylactic treatment consists in the exercise of great care in the administration of silver salts. Very small doses should be given, and for a very short time. Prescriptions of silver com- pounds should not be given to patients, and in all cases warning should be given as to the danger attending their use. De Schweinitz and others have given warning concerning the prolonged use of protargol. Aldred Scott Warthin. References. De Schweinitz : Trans. Am. Ophthal Soc, 1903. Eichmann : Husemann's Toxicologie, p. 871. Fourcroy: La medecine eclairee par des sciences physiques, Paris, 1791. Frommann: Virchow's Archiv., 1S59, xvii. Jacobi: Arch. f. exper. Path., 1S7S, viii. Kobert: Arch f. Derm. u. Syph., 1S73, xxv. Kramer: Das Silber als Arzneimittel betrachtet, Halle, 1S45. Liouville: Gaz. de med. de Paris, 186S. Loew:Pfliiger's Archiv. f. d. ges. Physiol., 1S94, xxxiv. Riemer: Arch. d. Heilkund., 1875, xvi. Rogers: Cited in Wood's Therapeutics. Scattergood: Brit Med. Jour., 1871. Versmanns: Virchow's Archiv., 1S59, xvii. Virchow: Cellularpathologie, 1S71, p. 250. Yandell: Amer. Practitioner, 1872. Aristol. — See Thymolis Iodidum. Aristolochiaceae.— (The Serpentaria Family). A small family of some five genera, widely distributed over the warm parts of the earth. A species of Aristolo chia produces one of the largest of known flowers, some five feet in length. Many species have been ignorantly reputed as antidotes to serpent poisons. Medicinally, the family, rich in volatile oils and resin, is well represented by Virginia, Texas, and Canada snake roots. Many species are used in native practice as vulneraries. H. H. Rusby. Arizona. — This ancient land and new State, situated on the Mexican border in the extreme Southwest corner of the U. S., offers to the archeologist, the geologist, and the climatologist a field of study if surpassing interest. Here prehistoric races once developed a civilization of no mean order, as evidenced by the traces of great public works still remaining. Here later came the Indian races, the ancestors of those still found here, in various degrees of civiliza- tion, to the number of 24,000 or more. Then came the intrepid and restless Spanish explorer and conqueror, accompanied by the Jesuit or Franciscan, exhibiting a self-denial and heroism only equalled by his brother in the Canadian wilderness, and devoting his energies to the bringing under Christian denomina- tion the native whom the Spanish warrior had subdued to Spanish rule. Later, the Presidios, established by the Spaniards, lose their hold, and the Friars are expelled. Indian wars arise, and the American comes. The Mexican War follows, and Arizona becomes American territory. After a stormy period of Indian and border warfare, with all the excesses incident to the occupation of new territory by a motley crowd of adventurers, the territory becomes more peaceful and grows in popula- tion and prosperity until at last, with a population of 204,354 (1910), it arrives, in 1912, to the dignity of statehood. Arizona, with the adjoining New Mexico, have been aptly called the Egypt and Arabia of America, for both in archeological interest and climatic character- istics, the resemblance is close. Especially is south- ern Arizona comparable with upper Egypt in the lowness of its humidity, the clearness of its atmos- phere, and the absence of vegetation. In general, 530 REFERENCE HANDBOOK OF TIIK MKDIC'AI, SCIKXCKS Arizona the climate of Arizona is a warm and very dry one. \, ., certain season of the year (between Ma\ anil October), the heat is extreme; and ai another season (April i" June), there is no rain. The thermometei . high as 130 F. and as low as —8 ' I''. 1 1 !,. rainfall varies from two to two and one-half Inches at various points in the lower Gulf valley and on the western borders, to twenty-five to thirty inches on the plateau and in the mountains. Tins scanty rainfall i~ distributed from July to April, with marked increase from July to September, and a lesser increase in December. In the holiest portions ne t ru e desert on the Mexican border, the daily maximum temperature is about 1 10° F., but owing to the rapid radiation, the temperature frequently falls ,i 50° at night. We may have ice at high levels ight and at midday the thermometer may reg- ister over 100° F. Such great diurnal variations of ure are characteristic of desert climates, and we have the same phenomenon in Egypt. These [en changes are not without risk, and one must ireful as to underclothing. It is safe to wear nels the year around. fhe sunshine is abundant. The proportion of perfectly clear days in the year varies at different points, from one-half to two-thirds, and of the rest more than one-half are without brilliant sunshine part of the day. In so large an area as is embraced in Arizona, with its varied topography, there is, of course, a wide variety of local climate, which is but the modification the general climatic characteristics, mentioned :ihi ive, by the latitude and local conditions of altitude, moist ure, soil, etc. There are three distinct topograph- ical regions into which Arizona divides itself, and within lin limits these regions have their own peculiar climatic characteristics. We have, first, in the : portion of the State, the great Colorado Plateau, 4.5,000 square miles in area, covering more than half the State, with an average elevation of 5,000 feet; second, a broad zone of mountain ranges running in a southeasterly direction; and, third, a on of desert plains embracing about one-third of the territory, lying in the southwest quarter, and of an elevation below 3,000 feet. The first, or plateau region, the high altitude re- gion of Arizona, large areas of which being from 6,000 i" s,(i00 feet in elevation, consists of a broken, rough, rocky region, with hills and isolated barren mountains studding the great elevated plain, and with few rivers running in narrow canons. On account of the mountain systems near which it lies, this division is one in which the rainfall is heaviest, being from ten to twenty inches. The climate is agreeable and temperate, the mean annual temperature being 45° to "ill F., quite like that of many of the northern States, but without their extremes. The summer temperature is moderate. At Flagstaff, the "Sky- light City," in the central portion of the State, with an elevation of about 7,000 feet, and which may be included in this region, the mean tem- perature for the hottest months does not ex- ceed 6S°. For the three summer months of 1901 (Weather Bureau Observations), the mean tem- perature was 64.6°. The highest temperature recorded was 92° and the lowest 30°. There were twenty-seven clear, thirty-three partly cloudy and thirty-two cloudy days during the period. The total rainfall was 4.56 inches and the number of rainy days was twenty-eight. For the same year 1901), for the three winter months, December, January and February, the mean temperature was 31.6° F. The highest 65° and the lowest -4°. The total rainfall for the year, at Flagstaff, in an average of fifteen years, was 16.97 inches. The mountain region has a width of from seventy to one hundred and fifty miles and consists of short parallel ranges of mountains, averaging from 7. IIIM) to 9, OIK) feet, with some higher peaks. The climatic characteristics of this region are similar to those of the plateau region men! toned abo\ e, and Pre- scott (5,320 feet), some eighty miles south of I lag- staff, may betaken as an illustration. For the three summer months of l'.MII the mean temperature was 70.5°; the bighe I L02° and the lowe i 33 '. There were IS clear, 36 partly cloudy and s cloudy days; and the number of rainy days was 21, the total rainfall being 5.29 inches. For the three winter months, December, January and February, the mean temperature was 39.1° F.; the, highest 70' and lie- lowest 1° F. The total rainfall for the year was 12 97 inches. Oracle in the southeastern portion of the State, about forty miles northeast of Tucson, with an elevation of 4,500 feet, may bo included in this mountain belt, and is known a< a health resort of im- portance, situated in a beautiful country, free from dust, and where good accommodations can he obtained. ()n account of its elevation, the climate is not what the latitude would indicate. For the three winter months, December, January, and February, the aver- age temperature is 45.8° F., and for the three sum- mer months, June, July, and August, 78.8° F. For the year 1901, there wen' 269 clear, fifty-eight partly cloudy, and thirty-eight cloudy days. The mean tem- perature for the year was 62.7° F.; the highest was 101° and the lowest 19. It is cooler and more bracing than Tucson. The third topographical division is the region of the plain, a desert occupying about one-third of the southwest quarter of the State, below the level of 3,000 feet. On this low plain the rainfall is only from two to six inches during the year, and, including the desert on the California side of the Colorado River, the records approximate the absolute minimum of rainfall of the world. In the lower valley of the Gila River, the highest temperature of the year is near 130°, and the mean for the hottest month, July, is about 98°, while the mean for the year is from 68.9° to 74.4° F. The night temperature is also high. From the dryness, there is a great amount of dust, particularly in summer, but with the completion of the great Roosevelt Dam seventy miles from Phoenix, which is said to confine the largest artificial lake in existence, a body of water one and one-half miles wide and twenty-five miles long — Phoenix and an area of thirty square miles about it will be transformed into an oasis and the dust annoyance will disappear. At the foot of the Gila Valley also the Reclamation Service will conduct water under the Colorado to irrigate large areas of the desert on the Arizona side. It is mostly in this plain or desert region that the winter health stations exist, affording an admirable climate in winter, but too hot in summer. Phoenix (1,108 feet), the capital of the State, population 11,134, is one of the best-known health stations in this region, and its winter climate is favorable for pulmonary tuberculosis, bronchitis, asthma, and such conditions as require a warm, dry climate without altitude. The annual average temperature at Phoenix is 69°. The average January temperature is 49°, and the average Jul}' temperature, 90°. The relative humidity is about forty-five per cent. The rainfall is seven inches, and for the winter 1.89 inches. There is a very large amount of sunshine, the percent- age of which is said to be greater at Phoenix than that recorded at any other U. S. Weather Bureau office. In the year 1900 there was said to be only five days in which the sun did not shine. The mean daily range of temperature is great, as in all warm desert regions under cloudless skies. The mean daily variability, however, that is, the difference in the mean temperature from day to day, is small. There is no fog, and the temperature rarely reaches the freezing-point. What is called the "sensible tem- perature (M. W. Harrington) is that which is supposed to be the temperature felt at the surface 531 Arizona REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of the skin, especially when the skin is exposed, is considerably lower than that indicated by the ordinary dry bulb thermometer, more nearly approxi- mating to that of the wet bulb thermometer, for the ible temperature depends upon evaporation, and the greater the dryness of the air, the greater the difference between the ordinary temperature and the sensible temperature. Hence, in Phoenix the sensible temperature ranges considerably lower — from 0° to IS (Hinsdale) — and the heat, in consequence, is less oppressh e. The writer recalls a June day in Phoenix when the thermometer registered nearly if not quite 100°, but when protected from the sun the heat was not oppressive. "It appears," says Mark W. Harrington, the former Chief of the Weather Bureau, "that in arid regions the reduction of temperature caused by evaporation (that is, the sensible tempera- ture) may make hot weather not onty endurable but agreeable and refreshing." Phoenix has good hotels and accommodations, reliable physicians, and isfrequented by tuberculous patients. The consump- tive, however, should not go to any health resort without the advice of a competent physician, and on arriving at the resort should at once place himself under a physician's care. Tucson (2,400 feet), population 13,193, is situated about 110 miles southeast of Phoenix. Being higher, the climate is more bracing and the air cooler than in the latter city. The annual average temperature is 69° and the average winter temperature is 57° F. The average relative humidity is forty-two per cent. The rainfall is twelve inches for the year. The roads are said to be good and the scenery attractive. The accommodations are fairly good. "Cases of tubercu- losis, neuralgia and rheumatism do remarkably well" here. (Hinsdale, "Climatology and Health Re- sorts.") Like Phoenix it is a winter resort. Yuma (140 feet), population about 3,000, is in the extreme southwestern corner of the State, at the junction of the Gila and Colorado Rivers. It is but a few miles from the Mexican border. The winter is the season for invalids, the summer being extremely hot. In the former season the climate is mild, dry, warm, and pleasant, and the peculiarities of the desert air are here best illustrated. The mean annual temperature is 72°, that for January 53° and for July 92°; almost exactly the same as the averages for Cairo, Egypt, except that it is a little hotter in summer. The mean monthly winter temperature is 56°. The average number of davs during the year above 90° is 163; below 32°, 4; cloudy days, 21 (mean for six years). (Solly.) In 1893, from April to October, inclusive, out of 214 days, 162 days were over 90°. The maximum temperature for the year was 111°. The average annual relative humidity is 46 per cent, and average annual rainfall 2.9 inches. Yuma is rightly famous for its sunshine and heat. The accommodations are ordinary. Castle Creek Hot Springs (2,300 feet), about fifty miles northwest of Phoenix, are situated in the foot- hills of the Bradshaw Mountains, in the midst of beautiful and striking scenery. The Springs are reached by a drive of four hours from Hot Springs Junction, over an excellent road, affording extended views of mountain and valley. The average max- imum temperature for the months from November to April, inclusive, for four years (1900 to 1904) was 72.16° F. and the average minimum for the same period, 44.67° F. In these observations the maximum temperature was taken in the shade during the day and the minimum during the coldest part of the night. For a period of three years the average number of clear days for the same portion of the year, November to April, was 160; of cloudy days, 15.6; of rainy davs. ."..:;. Months are said to go by without a cloudy day; and hardly a day passes throughout (lie year without some sunshine. The hot water l!o',\ from the crevices in the rocks at a temperature of 115°. Bathing takes place in the open pools, and may be enjoyed throughout the year. The character of the waters is that of a mild mineral water, contain- ing principally sulphate of sodium, chloride of sodium, and bicarbonate of lime. They are of benefit for rheumatism, anemia, and disturbances of metabolism. The climate is favorable for asthma, hay fever, chronic bronchitis with much secretion, convalescence from acute diseases, and various nervous disturbances. The accommodations are excellent, there being a well-equipped hotel with all modern conveniences, attached to which are a physician and nurses. Other localities in Arizona with a mild winter cli- mate are Tombstone (2,300 feet) in the extreme southeastern part of the state; Calabaras (about 4,000 feet); Nogales (4,000 feet); Huachuca (4,780 feet); Crittenden (4,100 feet). Comfortable accom- modations, however, at these places are questionable. There, are also various other hot and cold mineral springs. One of them, Agua Caliente, 100 miles east of Yuma, enjoys a local reputation for the cure of rheumatism, chronic skin diseases, and neuralgia. A sort of acclimatization has to take place when one takes up his residence in Arizona, especially if in the plain or desert region. The extreme dryness of t In- air exercises a marked influence upon the various secretions of the body. The skin becomes hard and rough, as there is no sensible perspiration; the upper respiratory tract becomes irritated, and we may have chronic inflammation of these passages; the lipa crack; cystitis is said to be not unusual (Hinsdale, loc. cit.) and the kidneys and bladder become irritated on account of the concentrated urine. Constipation is common and obstinate. One is also apt to lose in weight. On account of the heat, one is not inclined to take much physical exercise, and the common form of it — walking — is unpleasant and not without its dangers from the alkali dust. It is also to be remem- bered that in the plain country where most of the health resorts are situated, there is no vegetation, except where irrigation exists — it is but one great treeless plain, wonderful in its clear skies and perpet- ual sunshine, but desolate and dreary from its waste of desert sands. Edward O. Otis. von Arlt, Ferdinand. — Born on April IS, 1812, in Obergraupen, near Teplitz, Bohemia. His father was a village blacksmith of small means. He re- ceived the degree of Doctor of Medicine in 1839. His prepara- tory training as an ophthalmologist carried on under the guidance of Prof. J. N. Fischer. From October, 1S46, to July, 1S49, he acted as a temporary sub- stitute for the regular occupant of the Chair of Ophthalmology; from 1S49 to 1850 ae served as full Pro- fessor of this branch of medical science in the University of Prague; and from the latter dale until 1883J when, according to the laws of Austria, he was obliged to resign his chair, he was full Professor of Ophthalmology in the Fni- versity of Vienna. Although his official duties then ceased, he continued to interest himself actively in ophthalmology up to March 7, 18S7, the day on which his death occurred from senile gangrene. Fie,. 305. — Ferdinand Kitlrr von Arlt. 532 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arm and Forearm li is a fact, universally admitted, that Aril was one of the most conspicuous representatives and promote] of the science and art of ophthalmology in the nine- teenth century. He ranks as a worthj a ociate of such heroes in this special field as von Graefe and I londers. of his published writings the following de- serve to receive special ntion: "Pfiege der ^.ugen lt n gesunden und kranken Zustande, nebst einem lange ueber Augenglaeser, " Prag, 1846 (revised ion in 1868); " Krankheiten des Auges," 3 vols., j, 1851, LS53,and 1856; " Operationslehre, " Leip- lig, ls~l. In is.")."), In 1 became associated with Donders in the work of editing the"Archiv fur Oph- thalmologic, " founded by von Graefe. Pagel, from whose " Biographisches Lexikon hervorragender des neunzehnten Jahrhunderts" the present sketch has been compiled, says thai " Arit was a man ie intellectual powers, a. very close observer, and an ardent lover of truth. He was a very skif ul opera- a t nisi worthy diagnosticum, and an admirable lecturer. It is an interesting fact that von Graefe's decision to devote his professional life to ophthalmo- logical work was largely due to the influence exerted by Arlt." A. H. B. Arm and Forearm. — THE ARM. — The arm (or upper beginsat the lower anterior margin of the axilla, tin' lower border of the pectoralis major muscle, ami ends al the elbow-joint, where the joint capsule joins the humerus before and behind. The skin of the arm is similar in structure to that of other uncovered skin surfaces of the body, is thin, especially at the front and sides, loosely attached to lying structures, and is free from large hairs. Cephali head I Radial n it ifun- 1 A irj Ti iceps, ex- 1 - tn aal head / Biceps, short 1 head. Mnsculo-cut. n. j Median neri e jv^l— Brachial artery tlii — Basilic vein. Int. cut nerve. Ulnar nei \ e, Inf. profunda a f Triceps, in- 1 ternal head Triceps, long head. 1 .106. — Transverse Section of Arm just below Insertion of Deltoid I rom Joessel: "Lehrbuch der topographisch-chirur- .i Anatomie," Bonn, 18S4.J The superficial fascial layer contains fat tissue that rounds out the contour in the well-nourished, and especially in the female and female art figure. The brachial fascia (deep fascia) is derived from the deep fascia of the pectoralis major in front, and from the insertions of the ten's major and latissimus and their sheaths behind; from a prolongation of the deltoid fascia on the outer side, and, through the axillary fascia, from the deep fascia of the serralus magnus, upon the inner side of the arm. Coming together from these origins these fasciae join to form a thin but firm sheath from shoulder to elbow. Aris- ing from the external condylar ridge of the humerus and passing outward to meet this sheath is the ex- ternal intermuscular septum, which extends from the condyle to the deltoid tubercle. Arising from the internal condyle and the internal condylar ridge, and ■nding from the coracobrachial insertion to the v is the internal intermuscular septum. Just above the elbow this may be clearly felt as a whip- like firm cord. These two septa divide the arm into two regions, the front and the back. The front compartment of the arm contains bicep and brachialis; the coracobrachialis being added at. an upper third arm section, and the brachioradiali , and io a certain extent al o the extensor carpi radi- al is long us, a I a. lower third arm ection. The back compartment contains triceps andanconeu . These compartments contain also their respective blood and nerve supplies. The mu culo piral (radial) nerve passes backward, downward, ami outward, with its accompanying superior profunda (deep brachial) artery, through the intet eptal pace between the interna] and external heads of the triceps, from a point high up in the back compartment. In its course it supplies various blanches to the triceps muscle; and, through its posterior interosseous divi- sion, the anconeus. The musculocutaneous nerve pa es forward, downward, and outward from the brachial plexus in the axilla, through tin' coracobra- chialis and between the biceps ami brachialis above in the front i partment, supplying the e three muscles; (he brachial artery supplying this compart- ment throughout. Still lower down in the arm, above t he elbow, we ha \ e pi act ica 1 1 y in the external intermuscular septum the musculospiral nerve and the superior profunda artery, and within the enfolding of the internal inter muscular septum, the ulnar nerve and the inferior profunda artery. The conformation of the front of the arm is due to the form of the biceps, which rounds well forward. \i i he slight, groove at the inner and outer base ,,( the biceps are placed respectively the basilic and ceph- alic veins, which extend from their ana tomo i , at the elbow upward along the borders of the biceps to join their outlet, the axillary veins, at the inner and outer sides of the arm and shoulder. In association with the skin we find, forming the cu- taneous supply of the outer arm, from the shoulder to the wrist: circumflex, upper external cutaneous branch of the musculospiral, lower external cutane- ous branch of the musculospiral, and cutaneous branches of the musculocutaneous. In the skin and superficial fascia of the inner arm and forearm is the cutaneous supply of the inner arm and forearm: intercostohumeral, internal cutaneous branches of the musculospiral, lesser internal cutaneous (Wrisberg's), and internal cutaneous. A few small lymphatic nodes upon the inner side of the arm, just above the elbow, may be found in the superficial fascia near the course of the basilic vein. I I e nodes, enlarged, are pathognomonic of syphilis. The lowest point of the insertion of the deltoid marks the middle of the humerus, the middle of the musculospiral groove behind, the lower border of the coracobrachialis insertion, and the upper limits of the brachialis. The Front of the Arm. — Just within the anterior fascial compartment is the biceps, which lies upon the brachialis, while the latter, in turn, lies upon the anterior surface of the humerus. Along the inner border of these two muscles is the brachial artery. The artery winds about the humerus from the mid- axillary space, high up in the arm, to the internal septum in the mid-arm, to the anterior part of the brachium at the elbow. The terminal branches of the brachial plexus also conform to this route through the arm. The biceps arises from the scapula by two heads: the long head above the glenoid fossa of the scapula, the short head, in common with the coracobrachialis, from the tip of the coracoid process, from these two tendinous origins, these heads swell into long muscular bellies that converge and lie side by side in the upper third, and unite at the lower third of the arm. Toward the bend of the elbow the muscle libers converge upon a centrally placed short, stout tendon, which is inserted upon the posterior facet of the tuberosity of the radius, a bursa, not connecting 533 Arm and Forearm REFERENCE HANDBOOK OF THE MEDICAL SCIENCES with the joint, occupying the anterior facet over which the tendon plays when the forearm is flexed. As rarely happens a rupture of the long head of the biceps causes an egg-like swelling of the muscle just above the elbow; while the still more uncommon rupture of the tendon of insertion causes a large muscle swelling above near the insertion of the deltoid. Pus in the shoulder-joint often burrows out following the long tendon of the biceps to appear at the anterior of the arm just below the insertion of the pectoralis major tendon. Itis the tendon of insertion of this muscle that becomes so "lame" through pro- longed cranking of gasoline engines and motor cars; and it is the muscle proper that so often tires in pro- longed paddling. In pitchers the muscle-bundle tire of this muscle especially allows the spontaneous fracture of the humerus. The fascial sheath of the arm anteriorly, after becoming distributed to bony parts of the elbow and condylar ridges, receives in front of the elbow a strong, flattened band of fibers from the biceps tendon, the semilunar or bicipital fascia, which is continuous with the deep fascia above and is lost over the pronator teres below in the ulnar fascia. This fascia bridges over the brachial artery and separates it from the median basilic vein. The brachialis arises from the whole lower half of the inner and outer surfaces of the humerus, from the front of the internal intermuscular septum, and from a part of the external intermuscular septum above a point where the musculospiral nerve pierces it. Its origin em- braces the insertion of the deltoid. The muscular fibers converge broadly into a short, thick, tendinous insertion upon the coronoid process. This muscle is overlaid by the biceps, but projects be- yond it inward and outward. It is overlapped on the inner side by the brachial artery, by the median nerve, and by the pronator teres; also, deeply, by the anterior branch of the anastomotica magna and the anterior ulnar recurrent artery. Upon its outer side it [s overlapped by the radial recurrent artery, by the radial nerve, and by the brachioradialis and extenso- carpi radialis longus; also deepl)', by the musculo- spiral nerve ami by the terminal branch of the su- perior profunda artery. The coracobrachialis is an elongated muscle arising in common with the short head of the biceps from the tip of the coracoid process. It is inserted on the inner border of the shaft of the humerus at about its middle. It lies, in its lower part, along the inner border of the biceps, the two muscles lying to the outer side of the brachial artery. The brachial artery is the direct continuation of the axillary at the level of the lower border of the teres major. Therefore the lower half of the third por- tion of the axillary artery lies uncovered by muscle in the upper ami. The brachial extends a short distance below the elbow where it ends in its two ter- minal branches — the radial and ulnar arteries — on o Opposite sides of the radius near the junction of its head and neck. The course of the artery is sinuous; it lies at first internal to the humerus, slightly overlapped by the coracobrachialis above, then in front of the bone, slightly overlapped by the biceps; and, at the bend Of the elbow lies midway between the condyles. Compression of the artery at any point in the arm should be outward toward the bone above, outward and backward at its lower third, directly backward below. Throughout its course the artery occupies a position near the surface and can be felt pulsating. Not pulsating, it may be found upon a line drawn from the inner border of the coracobrachialis above to mid-elbow just internal to the biceps tendon. It lies at first upon the long head of the triceps, but is separated from the muscle by the musculospiral nerve and superior profunda artery, and is overlapped by the biceps. Next, it rests upon the inner head of the triceps, at the middle third of the arm, ami is overlapped by the insertion of the coracobrachialis. At its lowerthird, just before bifurcation, it lies upon the brachialis. It lies beneath the skin and fascia and is partially bridged over by the coraco-brachialis and biceps upon" its outer side. At the bend of the elbow it is overlapped again by the strong bicipital fascia, is crossed by the median basilic vein, and dips deep into the triangular (anti- cubital) space between the brachioradialis and the pro- nator teres. The sheath of the artery is closely incor- V porated with the deep fascia of the biceps, so that in ligation of the artery it moves in its position accord- ing as tension is put upon the muscle. The median nerve follows closely the artery and its sheath, lying first to its outer side, then in front of it, and finally toward the elbow at its inner side. The ulnar and the internal cutaneous nerves lie to the inner side of and behind the artery till about the middle of the arm, when the ulnar diverge- to pass well backward, to reach the internal intermuscular septum above the internal condylar ridge, where it enters the posterior compartment of the arm. The internal cutaneous pierces the brachial fascia ami pa forward just below the middle of the arm, and it lies between the brachial artery, to the outer side, and the basilic vein upon the inner, to be wholly super- ficial at the elbow. The musculospiral nerve lies for a very short distance behind the brachial artery upon the long head of the triceps before it is joined by the superior profunda branch and gains the musculo- spiral groove. Fig. 307. — The Inner Ann. Muscles contracted. (After Gerrish.) 534 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arm and Forearm The artery gives off the superior profunda, the inferior profunda, tlio anastomotica magna, t lu- QUtrient, the muscular, and the terminals — the radial and ulnar arteries. Tlit' superior prufu mln arlrri/ which lies first to the inner, then to the posterior side of the brachial, rises usually just below the teres major, perforates the septum, and then penetrates to the musculospiral >ove, in which it rims for a certain distance. It gives off above, an ascending branch that supplies ad£SL Fig. 308. — Course and Branches of the Brachial Artery. (Heitzmann.) the triceps and forms an important anastomosis with the posterior circumflex. The cutaneous branches follow the nerve and supply the skin over the outer arm. The articular branch is given off behind the external intermuscular septum and runs downward in the substance of the triceps, anastomosing with the interosseous recurrent below, and, across the joint behind, immediately above the olecranon fossa, by an arch with the anastomotica magna. The terminal branch perforates the septum to become anterior at the elbow, and it, anastomoses with the radial recurrent. It often gives off a nutrient artery or arteries to the upper end of the humerus, and it gives muscular branches to the triceps. The inferior profunda usually rises from the inner side of the brachial about opposite the lower part of the coracobrachial!- in 11 lion. It passes with the ulnar nerve through the internal intermuscular septum to the back of the condyle, and there, under cover of the tendinous aponeurosis of the lle\ or carpi ulnaris, it anastomoses with the- posterior ulnar recurrent- and ana tomotica magna. It supplies Ihe humerus, triceps, and elbow-joint, and it frequently gives Off a branch, that passes to the In ml of the joint and anastomoses with the anterior ulnar recurrent. The anastomotica magna usually rises from the inner side of the brachial, a short distance above the bend of the elbow, runs downward and inward across the brachialis, and divides into an anterior and a posterior branch. The anterior branch anastomoses in front of the internal condyle, beneath the pronator teres, with the anterior ulnar recurrent. From this branch a branch often passes behind the condyle to an- astomose with the posterior ulnar recurrent and the in- ferior profunda. The posterior branch perforates the internal sept uui, passes to the posterior surface of the internal condylar ridge, pierces the triceps, and there anastomoses with the articular branch of the superior profunda and with the interosseous recurrent. The nutrient artery is given off variably from the brachial or one of its branches and passes through the nutrient foramen, downward toward the elbow. After entering the shaft of the bone, a branch passes upward toward the head and neck. The muscular branches, from five to eight in number, are variably given off, from the outer side of the artery, to the coracobrachialis, the biceps, and the brachialis muscles, usually at the points where the nerves enter these muscles. The musculocutaneous nerve, arising from the outer cord of the brachial plexus, soon perforates the coracobrachialis, and, still inclining outward, reaches the bend of the elbow and there piercing the fascia becomes superficial just at the outer border of the biceps tendon. The Back of the Arm. — The triceps occupies the whole of the posterior compartment of the arm and is made up of three heads of origin. The long head rises by a flattened tendon from the upper part of the axillary border of the scapula and its adjacent lower glenoid rim. This tendon, with its muscle bundles, together with the outer (upper) humeral head, forms most of the superficial part of the muscle. The inner head, rising below the musculospiral groove, is more deeply placed. The muscle bundles from these three heads converge below into a short common tendon which is inserted into the posterior part of the top of the olecranon process. A bursa underlies the tendon over the rest of the top of the process. The long head is joined upon its inner side by a slip of aponeurotic fascia derived from the lower border of the tendon of the latissimus. The outer, or upper, head occupies all the posterior and external surfaces of the humerus from the teres minor insertion to the groove. It also has fibers which are attached to the external intermuscular septum and the ap- oneurotic sheath bordering the groove. The groove is free. The inner, or lower, head rises from the posterior surface of the humerus below the groove and receives a narrow-pointed slip from high up near the insertion of the teres major, upon the inner side of the groove. It rises also from the whole length of the internal intermuscular septum and from a small part of the external intermuscular septum. The fibers of origin of the long and outer heads join and form a broad, flat tendon of insertion. Some of the fibers of this tendon are given off especially over the outer part of the elbow-joint, and ultimately they expand so as to form a strong fascia that covers 535 Arm and Forearm REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the forearm. The short fibers of the inner head are in great pan inserted upon the deep surface of this tendon. A few fibers, however, are inserted directly upon the olecranon or into the posterior ligament of the elbow. The musculospiral nerve and the superior profunda artery supply muscular branches to each of the three heads. _ _ The musculospiral nerve is the continuation ot the posterior cord of the brachial plexus after there have been given off, in the axilla, the circumflex and the subscapulars. After passing for a short distance behind the lower part of the axillary artery and the upper part of the brachial artery, it dips backward, downward, and outward, from the position where it lies upon the lower part of the triceps, and then, alter being joined by the superior profunda artery, it enters the musculospiral groove. Not infrequently in fractures of the humerus at this point the nerve is pinched or stretched over a fragment or caught in repair callus with resulting "wrist drop." It turns round behind the shaft of the humerus and appears at the outer side of the arm, where, at about four inches above the elbow-joint, it pierces the external intermuscular septum and lies in the front compart- ment of the arm, deep between the brachialis on the inside and the brachioradialis and the extensor carpi radialis longus upon the outside. In front _ of the external condyle of the humerus it divides into its terminal branches, the radial and the posterior inter- osseous. It gives off three cutaneous branches, and supplies muscular branches in the arm to the three heads of the triceps, the anconeus, the brachialis (in part) the brachioradialis, and the extensor carpi radialis longus. The last three muscles are supplied by branches given off in the front compartment. The internal cutaneous branch usually rises in the axilla in company with the branch which goes to the long head of the triceps, and then passes back of the arm. It supplies a middle dorsal strip of in- tegument nearly as far down as to the elbow. The eT external cutaneous branch pierces the deep fascia in the line of the external intermuscular sep- tum at the upper third of the arm, accompanies the cephalic vein in the lower half of the arm, and sup- plies a -trip of skin, from exit to elbow, on the antero- extemal surface of the arm. The lower extern,,) cutaneous branch, which is much larger pierces the ia somewhat lower down, and supplies the skin of the middle of the back of the forearm as far down as to the wrist. In its course it passes between the internal cutaneous nerve upon the inside and the musculospiral upon the outside. The lesser internal cutaneous nerve ( Wnsberg s) rises from the inner cord of the brachial plexus, passes as far down, in the front compartment, a to the inner side of the axillary vein, which latter sepa- rates it from the ulnar nerve, at the middle ot the arm. At the elbow it turns backward to supply the skin over the olecranon. . The internal cutaneous nerve rises from the inner cord of the brachial plexus, and passes down the arm to the inner side of the brachial artery. With the basilic vein it perforates the deep fascia and supplies the skin of the upper and inner arm. Above the elbow the terminal branches, anterior and posterior, diverge slightly at the anterointernal side ot the arm, to pass the elbow, where they supply the skin of the inner forearm, anteriorly and posteriorly, as far down as the wrist. \ terminal branch of the musculocutaneous nerve p a , over the elbow and lies below in front of the radial artery. It supplies the outer side of the fore- arm, front and back. Should the shaft of the humerus need to be cut ,| (l ,i upon for wiring fracture, caries and the like, with least injury of the soft parts it may be done: (1) at its »/)/'"' third, anteriorly, at the anterior bor- der of the deltoid muscle just external to the bicipital groove, thereby avoiding the sheath of the biceps and severing "only the small anterior circumflex artery; (2) at its upper third, posteriorly, at the posterior border of the deltoid muscle, care being had in avoiding the circumflex vessels and nerve exposed above and the musculospiral nerve below; (3) at its lower third, posteriorly, by an incision posterior to the external intermuscular septum from the external condyle extended upward. THE FOREARM. — The forearm is that portion of the pectoral girdle or upper extremity lying between the elbow and the wrist joint. Its various structures are most intimately associated with the functions of the hand. Its bony framework comprises two bones, the radius and the ulna. The ulna is directly con- tinuous with the humerus, the radius with the hand and its functions and movements. The skin of the forearm is soft and is usually well supplied with hairs, especially along the postero- external surface. Along the anterior surface the hairs are fewer and finer. The skin is freely movable throughout the forearm upon the deep fascial sheath. The bursa over the olecranon gives it free mobility at that point. Lying within the layers of the super- ficial fascia are the superficial veins and the cutane- ous nerves. The superficial veins rise in two plexuses: the large plexus of the dorsum of the hand which is derived from the digital veins, and the smaller plexus of the front of the wrist, from the palm and thumb. These veins are larger than those of the deep set, have fewer valves and return most of the blood. At points of communication between these sets of veins, valves are regularly found. The vein's arising from these two plexuses are irregular in their distribution and are seldom sym- metrical upon the two sides in the same body. Foi convenience four principal vein trunks are distin- guished upon the outer, anterior, and inner surfaces of the forearm: the radial, the median, the anterior, and the posterior ulnar veins respectively. The median vein as it reaches a point opposite the inser- tion of the biceps receives a communication from the deep set which perforates the deep fascia. This trunk is short and is known as the profunda. The median at once divides into branches that diverge in V-form, the median cephalic to the outer side and the median basilic to the inner side of the biceps. The n,,, Han cephalic ascends to a point a little above the elbow, is joined by the radial vein, and this trunk, called the cephalic, lies in the furrow to the outer side of the biceps in the arm. The median cephalic vein overlies the cutaneous branches o : the musculocutaneous nerve as they pass the elbow. The median basilic vein passes upward and inward and is usuallv joined at a point about in front of the internal condyle by both the vlnar veins. 1M trunk so formed is called the basilic and lies to W inner side of the biceps in the arm. The median basilic is usuallv larger and shorter than the median cephalic; the basilic is usuallv a considerably larger trunk than the cephalic. The median basilic veil) overlies from without inward the bicipital fascial aponeurosis, the brachial artery, a part of the an- terior division and the whole of the posterior division of the terminals of the internal cutaneous nerve. Superficial Nerves.— The cutaneous nerves arc the musculocutaneous, with a few fibers from Uic musculospiral near the elbow, for supplying the outer side of the forearm, front and back; the internal cut aneous, for supplying the inner side of the forearm front and back. Lying between the two on the hack of the forearm is the distribution of the lower (larger) cutaneous branch of the musculospiral. All these nerves pass the elbow. Behind, over a small area, limited to the olecranon, is the nerve of \\ risberg. 536 KKFKIMAi !•: HANDBOOK o|' THE MEDICAL SCIENCES Arm ami Forearm Piercing the fascia at the Id wit third of the forearm, the following nerves become superficial or cutaneous: (he palmar branches of the ulnar, median, and radial nerves on the front, and the dorsal branch of the ulnar nerve and the radial nerve mi the back. The brachial (deep) at the elbow is j^_ firmly fixed to the bony p ro m i n e 11 ees , a ml is ■ihened ill fniiil by the bicipital fascia. This slip is given nil' from the on of insert ion of the biceps, which bridges o\ er the brachial artery, and is over the pronator and its sheath at the inner side of I he forearm. fascia! libers are al '• Often received from the hi of the triceps. her iii the upper third of the forearm this deep fascia forms a strong enveloping sheath. Near the elbow at the internal le it serves in part as the origin of several mus- hich spring from the condyle. Lower down in the forearm septa are given oil' from its deep surface to dip down be- tween the various muscle bellies. In the lower third the fascia is continuous with the various muscle ns and at the wrist forms the anterior and posterior annular liga- ments. It ends in the fascia of the hand. It is attached to the posterior triangular area of the ole- cranon and to the whole of the posterior ridge of the ulna, and is much thicker behind. Between the su- perficial and deep layers of muscles, front and back, is a thin membranous layer of fascia. Below and be- hind, the fascia is st rength- ened by transverse fibers to form the posterior an- nular ligament of the wrist which passes from the anterior border of the radius above the styloid process backward and in- ward, over the series of ridges forming grooves for tendons, over the ulna serving as an orbicular ligament, to attach itself to the inner aspect of the wrist, especially over the pisiform and cuneiform bones. Muscles. — The muscles of the forearm, for con- venience, can be divided into groups: those of the front, those of the back, and those of the outer side of the forearm. Those of the front (anterior radio- carpal) consist of a superficial set, five in number: the pronator teres, flexor carpi radialis, flexor carpi ulnaris, tlexor digitorum sublimis, and (flexor) pal- niaris longus; and a deep set, three in number: flexor digitorum profundus, flexor pollicis longus, and pro- nator quadratus. The muscles of the outer ide i radial), three in number, are: brnchioradialis, extensor carpi radialis longus, and extensor carpi radialis brevis. 'I'll., e ..I the bad (po terioi radio- carpal) comprise a superficial set, four ill number: extensor digitorum communis, extensor digiti minimi, extensor carpi ulnaris, and anconeus; and a deep set, five in number: supinator (brevis), extensor ossis metacarpi pollicis, extensor pollicis longus, extensor pollicis brevis, and extensor mdicis. The five muscles of the superficial flexor group are intimately associated at their origin from the internal condyle. Arising from it is a tendon common to them all, which gives libers to each and sends septa between every two contiguous muscles. The muscles, from without inward, are the following: 537 Arm and Forearm REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The -pronator teres, the most external, crosses ob- liquely the upper half of the forearm. It rises by two heads: one, large and superficial, from the inner condyle of the humerus by a tendon common to both S < a & heads, and from the supracondylar ridge, fascia, and intermuscular septa; the other, a thin and deep band, coming from the inner side of the coronoid proci and sunn joining the deep surface of the large head. This slip separates the median nerve from the ulnar artery, The muscle thus formed passes outward anil ends in a Battened Irndon which turns over Hie radius and is inserted into a rough impression on the outer surface of the shaft of the radius about at its middle. Near the insertion the muscle is crossed by the radial artery and is covered by the brachio- radialis. The flexor carpi radialis rises from the flexor tendon, from fascia, intermuscular septa, and adjacent muscles. At about the middle of the forearm its fleshy belly merges into a long flattened tendon, passes in a special compart- ment of the anterior annular ligament, grooves the trape- zium, and inserts itself into the base of the second and frequently into the third metacarpal bone. The (flexor) palmaris longus is a long slender muscle, the smallest of the group. It rises from the flexor tendon, fascia, and septa, to form a small round belly. It soon ends in a long slender tendon which inserts itself into the lower border of the annular ligament and the palmar fascia. This muscle is very variable and is often absent. The flexor carpi ulnaris, the innermost muscle of the group, rises by two head-: the one from the back part of the flexor tendon, the other from the inner side of the olecranon and, by an aponeu- rosis, from the upper two- thirds of the posterior border of the ulna. The two heads bridge the space between the internal condyle and the ole- cranon and between and be- neath them the ulnar nerve is transmitted. The muscle converges into a tendon which is placed along its front surface and inserts itself into the pisiform bone. The flexor digitorum sub- limis (flexor perforatus) is a broad flat muscle placed be- hind the preceding. It rises by a strong head from the flexor tendon, from the in- ternal lateral ligament of the elbow-joint, from the inner border of the coronoid proc- ess, and from the overlying muscles and septa; and by a second head, a thin flat band, from the anterior oblique line of the radius and its anterior border. It merges from a broad muscle into four sepa- rate tendons which first pass through the middle compart- ment of the anterior annular ligament, then diverge, and continue their course, each one separately, in company with a corresponding ten- don from the profundus (behind), to each of the lust four fingers. At the wrist the tendons pass in pairs, those for the third and fourth fingers being in front, those for the second and fifth lying behind the first pair. The tendons opposite the first phalanx divide, allow the profundus tendon to pass between, then unite behind to insert themselves into the second phalanx. 538 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arm and Forearm ■ This group of muscles is supplied by the median nerve, save the ulnar flexor which receives its supply from the ulnar. . . The '/' i p-si 'ii' 'I flexor group comprises the following muscles: . The /?' j''"' ilii/ii'intm profundus (flexor penetrans;, •i large thick muscle, rises from the upper three- fourths of the front and inner side of the ulna, from the ulnar half of the in- -e U S in b ra ne and from the urosis ol the flexor ulnaris. It divides \ Bnallyinto four ten for the inner four fingers, but the tendon for the index becomes dis- tinct in theforearm. tsses behind the sublimis at the wrist, behind the sub- limit tendons in the palm, and perforating the sublimis inserts itself at the buses of the phalanges of the inner four fingers. The lumbricales take origin from its tendons in the palm. The flexor pollicis longus, to the outer side of the profundus, rises from the front of the radius between the oblique line and the pronator quadratus, the adjacent interosseous membrane. From a fleshy belly, a round tendon passes under the annular ligament thenar eminence to its insertion at the base of the id (last) phalanx of the thumb. Occasionally a second head rises from the coronoid process or internal condyle in common with the sublimis. The pronator quadratus rises from the pronator ridge and from the front of the ulna at its lower fourth, passes close to the bones, and inserts itself into the front of the lower end of the radius. This group of muscles is supplied by the anterior interosseous branch of the median nerve; with the exception that the ulnar nerve supplies the outer half of the deep flexor, i.e. the ring and little fingers. The muscles of the outer (radial) extensor group are: The brachioradialis (supinator longus) rises from the upper two-thirds of the external supracondylar ridge and from the front of the external intermuscular septum. It forms a long slender muscle which, near the middle of the forearm, merges into a flat tendon: and this, in turn, inserts itself into the outer side of the radius near the base of the styloid process. The extensor carpi radialis longus rises just below the preceding muscle from the ridge and septum, a few fibers being derived from the common extensor ten- don. From this origin a long tendon passes under the posterior annular ligament in its second compartment and passes to its insertion into the base of the second Fig. 313. — Skiagraph Showing Relations of Bony Framework of the Shoul- der, Arm. and Elbow to the Soft Parts which Sur- round Them. (After Ger- rish.) icarpal. In its course ii lie- upon the following muscle. The extensor carpi radialis brevis rises by the com- mon extensor ten. Inn from the external condyle of the humerus, from the intennu epta, and from the external lateral ligament of the elbow. lis tendon passes with the longus in the same compart- ment at tin' wrist and is finally inserted into the i, of the third metacarpal. This muscle group is supplied by the mUSCulo- spiral nerve, that to the short radial extensor being through the posterior branch of the nerve. The group from without inward, contains the following muscles: Tile by the c - iiiiin extensor tendon, fascia, and septa. 1 rom a fleshly belly four tendons are ultimately given off, and these pass through the fourth compartment of the posterior annular ligament on their way to the hand. Here they diverge ami then pass on to the points where they are inserted at the bases of the id and the third phalanges of the inner four fingers. The. extensor digit! n lies a! the inner side of the preceding muscle. It rises in the same manner as does that muscle and passes through the fifth com- partment at the wrist (between radius and ulna); its points of insertion are the same a- those of the corre- sponding tendon of the preceding muscle. The extensor carpi ulnaris rises in the same manner as the preceding, and also by an ulnar aponeurosis common to it, the flexor carpi ulnaris, and the flexor profundus. The tendon emerges near the wrist, passes in the sixth compartment, and i inserted into the base of the fifth metacarpal near its ulnar border. The anconeus rises from the lower part of the back of the external condyle and from the adjacent pos- terior ligament of the elbow and is inserted into the outer surface of the olecranon and the upper third of the back of the ulna. This muscle is sometime-; continuous with the triceps and is usually described in connection with it, as a fourth head. This group is supplied by the posterior interos- seous branch of the musculospiral nerve. The deep extensor group comprises the following: The supinator (brevis) rises from the back of the external condyle, the external lateral ligament, the orbicular ligament of the radius, and the back part of the bicipital hollow of the ulna, from which point it extends a variable distance down the outer border of the ulna. Over these fibers of origin is a strong aponeurotic cover. The muscle passes out and down over the back of the radius to insert itself into the back of the neck of the radius and upon the outer and front surfaces of this bone as far down as the insertion of the pronator teres. The muscle is divided into superficial and deep layers by the posterior interosseous nerve as it passes to the back of the forearm. The extensor ossis metacarpi pollicis (abductor pol- licis longus) rises from the outer part of the back surface of the ulna at the junction of the upper and middle thirds, from the corresponding portion of the interosseous membrane, from a small part of the back of the radius near its middle, and from intermuscular septa. The muscle extends down and out, emerges between the extensor digitorum communis and the extensor carpi radialis brevis, and in company with the extensor pollicis brevis it crosses the two radial extensors. At about this point it merges into its tendon, follows down the outer side of the base of the radius, and enters the first compartment of the posterior annular ligament. It is inserted into the outer side of the base of the first metacarpal bone and by its aponeurosis into neighboring structure-, nota- bly the back of the trapezium, and also into the pal- mar fascia, especially that part which covers the thumb. 539 Arm and Forearm REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The extensor pollicis brevis (extensor primi inter- nodii pollicis) rises from the middle of the back of the interosseous membrane just below the preceding, from the back of the radius extending obliquely outward and downward, and from the intermuscular septa of this group of muscles. It extends obliquely down and out and forms its tendon at the lower third of the forearm. From this point it accompanies the tendon of the preceding muscle, lying behind it, to lie inserted into the base of the first phalanx of the thumb. The extensor pollicis longus (extensor secundi inter- nodii pollicis) rises from the outer part of the back of the ulna at its middle third, close to the outer border, from the interosseous membrane, and from the septum between it and the extensor indicis. This muscle, somewhat stronger than the preceding, passes down and out to merge into a tendon placed along its back. The tendon becomes free just above the posterior annular ligament, passes through its third compartment, then over the radial extensors, lies close to the inner side of the tendon of the pre- ceding, and is inserted into the base of the second phalanx of the thumb. The extensor indicis rises from the back of the ulna (from a [joint just below the preceding muscle to one situated nearly at the lower end of the bone), from the adjacent interosseous membrane, ami from the septum between it and the preceding. It merges into a tendon which is placed along its radial border. This becomes free at the lower third of the forearm, passes through the fourth compartment beneath the tendons of the extensor digitorum communis, and after it emerges from this it is inserted into the inner border of the tendon of the common extensor of the index finger at about the metacarpophalangeal joint. This muscle group is also supplied by the posterior interosseous branch of the musculospinal nerve. Arteries. — The brachial artery ends just below the bend of the elbow where it divides opposite the neck of the radius into its two terminals, the radial and the ulnar. The radial artery, the smaller of the two, extends downward, in direct continuation of the brachial artery, along the outer side of the front of the forearm to the lower end of the radius. Here it turns around the outer side of the radius to the back of the wrist, over the external lateral ligament, and under the extensors of the thumb. In the upper forearm it lies in the outermost inter- muscular space between the brachioradialis and the pronator teres, and is covered by fascia? and skin. In the middle and lower thirds of the forearm it lies along the inner border of the muscle and tendon of the brachioradialis, which latter serves as a guide in the operation for ligating this vessel. In this part of the forearm it is covered only by fasciae and skin, and by a few superficial veins and cutaneous branches of the musculocutaneous nerve. The radial at the wrist lies directly upon the bone, and forms the pulse. The radial nerve approaches the artery above at an acute angle; in the middle and lower thirds it lies along its outer side. The venae comites accompany the artery on either side. The radial artery in the forearm, besides the irregu- lar and numerous muscular branches, gives off the radial recurrent, the anterior radiocarpal, and the superficial volar. The rail in} rerun-, ,.',. a branch of considerable size, is usually given oil from the outer side of the radial just below its origin from the brachial. It runs out- ward between the brachioradialis and the supinator (brevis), divides into several branches and anastomoses with the interosseous recurrent and superior profunda, and gives of! a branch to supply the elbow-joint. The superficial volar and the anterior radiocarpal are brain In i en oil' just above the wrist. The ulnar artery, the larger of the terminals of the brachial, from the inner side of the neck of the radius l>a~It, vtuecuC ffl Tenia fiLsjp. long. !' M. ulnar im. 'It. dorsal Fig. 314. — Course and Branches of the Arteries of the Forearm (Heitzmann.) In the upper half of its course the artery lies deeply beneath the pronator teres and the superficial flexor-; in the lower half of the forearm it is overlapped only by the flexor carpi ulnaris muscle and tendon which lie to its inner side and serve as a guide in operations for ligating the vessels. Only in the last inch or so is the artery superficial. As the artery lies beneath the pronator teres it is crossed from within outward by the median nerve, the deep head of the muscle 540 KKl'KliKNCK HANDBOOK OF THE MEDICAL SCIENCES Ann and Forearm usually separating the two. The ulnar nerve ap- proaches the artery from behind the inner condyle at an acute angle, being separated from it l>\ the flexor ublimis, and in the lower two-thirds ii lies close to th e i nner s ide of the artery. The latter is covered by superficial ulnar veins, in addition to fasciae and i is crossed by branches of the internal eu- tane'o ' he arterj is ace panied by two coniites. The ulnar artery, besides m tous and irregular muscular branches, gives off the anterior and n current ulnar, the anterior and postei ior llS| the anterior and posterior ulnar carpal, i-illv the nutrient of the ulna. The anterior recurrent ulnar, the smaller of the two branches, runs up in front of the inner con- dyle of the humerus, be- en the pronator teres and the brachialis, and anasi omoses with the an- terior branch of the an- astomotica magna and a branch of the infei ior pro- funda. The ' poxt< Hot r< current ulnar, the larger, passes inward bet ween I he flexor sublimis and the flexor profundus, then up and back of the inner condj le of the humerus, and t 3 to lie, with the ulnar nerve, ctween the two heads of he flexor carpi ulnaris. t anastomoses with the osterior branch of the nastomotica magna, ith the inferior profunda, nd with the intern eous recurrent to form the ole- cranal rete. The interossei rise from the ulnar by a common trunk about half an inch in length from the outer and back part of the ulnar just be- fore the median nerve crosses the main vessel. This trunk arises about an inch below the origin of the ulnar, and proceeds back- ward to the interos- seous membrane, where it divides into its two terminals. The anterior inter- osseous, the smaller, fellows the front of the membrane in company with two veins and the deep branch of the median nerve which lies to its outer side. It usually supplies nutrient branches to both bones. rhe posterior interosseous, the larger, passes back a the interosseous membrane and the oblique ligament above, descends between the superficial and de ip muscles, and, crossing the extensors of the thumb and index finger, anastomoses below the latter mus- cle with the anterior interosseous. These ulnar recurrent and interosseous branches supply in main the muscles of the forearm, the large of the radial and ulnar passing through to supply the wrist and hand. rhe anterior and posterior ulnar carpals are small carpals which, in company with the anterior radial carpal, anastomose and form the carpal arch. Yir.. .'. . Eti gion of Wrist, showing Arrangement of Tendons, Ar- tery, Nerve, etc. The skin and fasciffl been removed. (After M. H. rdson.) .\ii:\i in iks. rhe nerve trunks of the forearm are the radial, posterior inteross - median, and ulnar. The musculi tior) distance abo> e the elbow, lying upon the brachialis and covered by the brachioradiali , divides into its terminals, 'lie |" rior interosseous and the radial nerves. Tin 1 >ack, out . and down between the brachialis and i carpi radialis longu . through the supinatoi o the leep layer. if the forearm extensors. It approaches the posterior intei i artery at an angle, and is in relation with it as far as to a point bi i in of t he e\iii, i ir pi illici li mgu where it approach and is in relation with the posterior branch of the anti rioi interosseous artery. Lower down, it pa es thro the fourth compartment of the wrist, with the exten- sores communis and indicis, to the back of the wrist e ii be is ganglionic. The radial nerve passes directly downward under co er of the brachioradialis. At the middle third Of the arm it lies along the outer side of the radial artery, then winds around the outer side of the radius under cover of the brachioradialis tendon, and pierces the deep fascia iii the lower forearm, breaking up into its terminal branches on the back of t he w rist. The' median nerve, from the bend of the elbow, where it lies to the inner side of t he tendon of t he biceps, the brachial, and the beginning of the ulnar artery, passes down the center of the front of the forearm beneath the condylar head of the pronator teres and over the ulnar artery, being separated from the latter by the deep head of the same muscle. Beyond this point it passes beneath the radial head of the flexor digitorum sublimis, and later still it lies deep beneath the flexor sublimis and on the flexor profundus. At the wrist the nerve becomes superficial and lies be- tween the tendons of the flexor sublimis to the inner side, and of the flexor carpi radialis on the outer side. It passes superficially through the large flexor com- partment of the anterior annular ligament and soon divides into an inner and an outer terminal. Besides muscular brain lies in the forearm, the median gives off thi' anterior interosseous and small branches to the elbow-joint. The anterior interosseous nerve is given off from the median opposite the insertion of the biceps, runs down the front of the membrane in company with the anterior interosseous artery, and supplies the med- ullary arteries, the periosteum of the radius and ulna, and the wrist-joint. The xdnar nerve, from the angle between the ole- cranon and the internal condyle, passes between the inner and outer heads of the flexor carpi ulnaris to the front of the forearm. It passes down upon the flexor profundus under cover of the flexor carpi ulnaris and overlapped by it upon the inner side. It passes nearly to the wrist along the outer side of this muscle and its tendon, when it becomes superficial and enters the hand anteriorly to the annular ligament. In the lower two-thirds of the forearm the ulnar artery lies to its outer side, separating it from the flexor sublimis. It also, besides giving off mus- cular branches, supplies the elbow-joint. The interosseous membrane bridges across between the interosseous borders of the radius and ulna from a point a little below the bicipital tubercle of the radius to the wrist-joint. Its fibers pass mainly in an oblique direction from the radius to the ulna. The posterior interosseous vessels pass back over its upper border and are in relation with its back surface low down in the forearm. The anterior interosseous vessels and nerve are in relation with the front sur- face throughout. Except in supination of the fore- arm and in full pronation this membrane is usually tense. It serves also to carry strains from the radius to the ulna and to bind the bones together. oil Arm and Forearm REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The forearm is subcorneal, so that the lateral flap operation is a necessity, since the skin cannot be pushed far upward in the lower forearm. The skin is also quite adherent to the underlying aponeurosis. Roughly speaking, the intermuscular septa, the bones, and the interosseous membrane form a front and a back compartment. The ulna is subcutaneous from olecranon to styloid process, so that any injury or fracture is readily manifest. The radius lies deeply lodged among the upper forearm muscles and it is only occasionally that its head can be felt. In the lower forearm the radius becomes gradually sub- cutaneous and can be examined. The interosseous membrane is tense in the semiprone position of the foicarm, which indicates the best position, in fracture of the radius or ulna, for splinting. Care should be exercised not to permit the fractured ends of the Fig. 316. — Dissection of the External Region of the Right Wrist The radial artery is seen between the relaxed tendon of the flexor carpi radialis below, and the braehioradialis on the outer (upper) side. It then passes beneath the first two extensors of the thumb and a small branch of the radial nerve, crosses the base of the thumb obliquely, and disappears under the tendon of the extensor pollicis longus. (After M. H. Richardson). radius to rest upon the ulna, thereby causing injury to interosseous vessels and nerves and favoring an eventual ankylosis. Anteroposterior splints may press too much upon radial and ulnar vessels and nerves and injure them. The muscles of the forearm in extremely muscular subjects after too long and severe use may cause pressure upon arteries and nerves, and resultant pains and neuralgias. Muscular spasm may effect the same results. Muscles become greatly hyper- trophied under special exercises (as occurs, for ex- ample, in the pronator teres muscle of the "tennis arm"). A spasm of the same muscle may take place, as in the "glass arm" of baseball pitchers. Hypertrophy of both of the pronators, the result of "feathering," may take place in the ease of oarsmen. The inner edge of the braehioradialis is the guide to the radial artery and nerve; the inner edge of the pajmaris tendon is that for the median nerve; and the outer border of the flexor carpi ulnaris indicates where the ulnar artery and nerve are to be sought for. Both arteries may be ligated at any point above the annular ligament for severe hemorrhage of the palm. Above the anterior annular ligament the two synovial tendon sheaths of the flexor pollicis longus and thai common to the sublimis and profundus extend for a distance of an inch and a half, and often carry infec- tion from the palm to the tendon spaces of the fore- arm. In case of pus spreading deeply up the forearm the median nerve should be used as a guide and ion- made upon either side of it. Through the posterior annular ligament extend upward six such sheaths, all of which save the la i extend well above the ligament. They are: one for the two outer thumb extensors, one for the two radiocarpal extensors, one for the long thumb ex- ten, or, one for the common extensor, one for the little finger extensor, and lastly one for the ulno- carpal extensor, suppurative. Injuries of the symptoms. (See These sheaths are seldom nerve trunks may cause varying the Section on the Arm.) The posterior interosseous nerve may be injured in resec- tion of the head of the radius or in fracture of the radial neck, and thus may cause paralysis of the extensors. The posterior interosseous nerve may suffer loss of function from fracture of the humerus at some point near its middle. Pressure upon the me- dian nerve in muscular spasm and in compression from long and severe muscular exercise, may cause in- creased cramps and pain or even a prolonged neu- ralgia. The ulnar mrve may be injured in fracture of the olecranon and may cause loss of sensation, or numbness; or it may becaught in the callus of fracture, either there or along the shaft of the ulna, and cause pain; and, finally, the conditions may be such as to necessitate excision of the nerve from the callus. The numbness from a sudden blow upon the ulnar nerve at the elbow — commonly spoken of as "striking the funny bone"— is a familiar instance; and if severe, this numbing and tingling may be persistent and may be accompanied by loss of function of the flexor muscles. In plumbism the ulnar nerve is regularly involved, causing the "claw hand." The ulnar and median nerves are both involved in alco- holic neuritis. The radial nerve may be painful at its points of distribution if the trunk is injured in Colles' fracture. Neuromata along the nerve trunks, due to injury, may demand excision. Luzerne Coville. Arm and Forearm, Diseases and Injuries of the. — In considering the diseases and injuries of the arm ami forearm, I shall take up the different affections of the several structures under the following heads: I. Affections of the Skin; II. Affections of the Fa.-cia; III. Affections of the Bones, the Periosteum, and the Joints; IV. Affections of the Muscles, Tendons, and Tendon Sheaths; V. Affections of the Blood-vessels; VI. Affections of the Lymphatic Vessels, Glands, and Bursas; VII. Affections of the Nerves; VIII. Hyster- ical Lesions; IX. Tumors. It will be my purpose to discuss more fully .those affections of these different structures which show some peculiar manifestations when presenting them- selves upon the upper extremities, and to deal with them less in detail when exhibiting upon the arm merely those features which are common to the same affections elsewhere in the body. Particularly in the case of diseases affecting the skin of the arm and fore- arm, not all the dermatic affections which may be found in this locality will be entitled to extensive con- sideration, but such forms of skin trouble only as are particularly prone to develop their lesions upon the arms. Furthermore, it will suffice with regard to must of these to call attention to the fact that certain lesions may be expected on the arms and forearms, and to describe their symptoms and appearance with sufficient accuracy to allow of their diagnosis, while more extended consideration of their pathology and treatment is to be sought under other headings in this work. I. Affections of the Skin. With regard to the diseases affecting the skin of the arms, we have to content ourselves for the most part with recording the observed fact of their appearance in this locality, owing to our ignorance of the causes that determine the outbreak of cutaneous lesions upon this part of the body. It is necessary to bear in mind that the general prin- 542 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ann and Forearm, Diseases and Injuries <»f * dplea of dermatology are applicable here as in other parts of the body, notably those which teach us thai symmetrical lesions may generally bei ideredtobe ,li, r in internal causes, while for unsymmetrical lesions there is a priori reason to think of local irritation as a oause of the affection. Similar weight .should ln- givcn in considering the relation of the cutaneous lesion to the clothing of the part, inasmuch as certain lesions are prone to appear on unprotected parts, while others appear where the fricl ion of the clothing, or vermin which the clothing may harbor, may give i to local irritation. Other matters concerning the of lesions of the skin on the arms, whieli may alTeet the diagnosis, are the lines of cleavage of the skin, and the presence of (lie lesions upon (he flexor or upon the nsor surface of the affected limb, and finally the in course of certain of the brachial nerves and els. Nor should the general rule of der- itological practice be forgotten which teaches us to compare the integument of the arms witli that of the of the body and so gain an accurate knowledge of the anatomical distribution of the cutaneous lesions. I In more recent nosological systems of dermatology have sought in group the various lesions of the skin ac- . irding to their pathological basis, and in the rapid a which I purpose to make of such cutaneous lions as have their common site upon the arms and forearms, I shall consider the different lesions in the general order of the classification of Jessner — to wit, functional disorders, circulatory disorders, and inflammations, superficial and deep-seated; finally, I shall consider briefly traumatisms of the skin. Functional Disorders of the Skin. — Of the first class, that of functional disorders of the skin, such as pruritus, hyperidrosis, seborrhea, it will suffice to say that none of them have any predilection for the arms or inns which would justify their consideration here, if we except the entirely unimportant erythema Bolare which is frequently seen on the arms of farmers, bathers, and laborers who work in the open air with i in sleeves rolled up. Circulatory Disorders of the Skin. — Of the dis- eases of the skin classified by Jessner as circulatory disorders, the lesions of purpura and scurvy, while undoubtedly they show themselves with comparative frequency on the arms, yet it is rare that they should show themselves there with any special preponderance of distribution over other parts of the body. Peliosis rheumatica, however, is a purpuric affection whose predilection for the arms merits our attention in con- sidering the cutaneous affections of these members. In I'ELiosis rheumatica, also called purpura rheumatica, a period of invasion precedes the erup- tion for a variable length of time, and is shown by general malaise, systemic disturbances and painful swelling of the joints, especially of the knees, wrists, and ankles. The temperature may be normal, but more often it rises to 100° F. or more. In a few days the eruption appears and the pain then subsides. The lesions occupy practically the same regions as do those of erythema multiforme (vide infra), namely, the wrists, forearms, and lower legs, but sometimes they are particularly located about and around the inflamed joints. Some authorities indeed classify the affection as a variety of erythema multiforme. The lesions consist of bluish-red patches, and slightly elevated, bright-red papules which quickly become purplish; they may, however, be purpuric from the first. Their color cannot be effaced by pressure. After persisting for a few days, they pass through the various gradations of color seen in a contusion and disappear altogether. The disease may be limited to outbreak, or the eruption may come out in several crops and run a course of from four to six weeks, or it may disappear altogether and ten days or more later a relapse occur, and the joint and other symptoms again become manifest. The recognition of hem- orrhage into the skin is easy when it is borne in mind that pressure does not cause the redness to fade. Such lesions occupying the localities mentioned, ami a o ciated with the systemic disturbance already de- scribed, with the joint swellings, pains, etc., are sufficient to constitute the diagnosis of peliosia rheiimal ica. Inflammatory Diseases of the Corium mid Sub- cutis. of the inflammatory diseases of the skin, we can at once dismiss the specific exant hemal oil : fevers of childhood as having no special predilection for the arms, and of i he di eases under the nosological classification we are following, that known a lichi i planus is the fii'st that arrests our attention. This is a disease whose predilection for the arms as a site for eruption is more marked than is the ease in that just described. Indeed, if is often confined to the flexor aspect of the forearm, though it manifests a tendency in its course to spread over a greater part of the lower arm and of the forearm; but ii never involves the whole skin as do eczema, psoriasis, and lichen ruber in certain cases. The following description of the symptoms and course of t he disease is taken from Gottheil: Lichen planus occurs most frequently as a chronic ami localized malady, the more acute and general form of the disease being rare. The site of i he eruption is usually the flexor surface of the fore- arms, especially around the wrists and on the backs of the hands and the feet, but other regions are not infrequent ly affected, and it occurs occasionally on the palms, soles, and (he genitals. It is rare, however, on the face and scalp. It is frequently symmetrical. The lesions appear first as extremely minute papules of a characteristic dusky red or purplish color, with a waxy glance, and sharply differentiated from the surrounding skin. Their sides are steep, and (heir shape is distinctly angular. Their tops are Hat. and marked with a central depression or capped with a minute scale. On the palms and soles the individual lesions may be hard to distinguish, the entire epi- dermis of the affected region being elevated and thickened, cracked in places and of a dusky hue and covered with whitish scales. On the mucosae they appear as whitish, flattened papules. They may be scattered or irregularly grouped. As they gradually enlarge to pea size, adjacent papules coalesce, and thus extensive indurated and scaly areas are formed; but the individual lesions do not increase beyond their original size. After persisting for a long time, months and years, they slowdy undergo absorption, leaving atrophic, pigmented areas behind. No vesicles or pustules are ever formed, nor are the nails or the hair affected. The subjective symptoms are confined to a moderate itching, and it is only in very extensive forms that this becomes severe. The patients are sometimes debilitated and run down by excesses or overwork, but not infrequently they are in excellent health. The malady occurs with about equal frequency in both sexes. It is seen at all ages, but is most frequent during middle life. The diagnosis rests upon the peculiar shape, size, grouping, and appearance of the papules as described above. Papular eczema, especially when situated on the forearm, may resemble lichen planus, but the papules are rounded and frequently have a little serum at their apices. They are intensely itchy, round, run a rapid course, and leave no pigmentation behind; and other eczematous changes, excoriation, oozing, or crusting will probably be found somewhere on the skin. In the papular syphiloderm the lesions are round-topped and often arranged in crescentic or circular form; they are generally distributed, and more or less polymorphic; there is no itching, their color is reddish. Other signs of syphilis are probably present, and the disease responds to antiluetic treat- ment. In lichen scrofulosum the round papules are grouped upon the trunk and are accompanied by no subjective symptoms whatsoever. Finally in psori- asis the lesions are pink, covered with abundant, 543 Arm and Forearm, Diseases and Injuries, of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES heaped-up scales, and are situated solely on the extensor surface. The prognosis is favorable always. The disease is chronic and obstinate, but it tends to recovery. It may be added that the disease, though not common, is K it excessively rare. The grave progressive disease known as lichen HUBEH may have some of its characteristic lesions situated upon the arms, but its distribution is so rarely limited to that locality that its discussion need not detain us here. When present upon the arms its tendency to follow and accentuate the folds and lines of cleavage of the skin sometimes leads, in the cubital folds, to the development of linear strings of papules, constituting what is known as "lichen ruber moniliformis." Few of the forms of eczema confine themselves to the arms, though small patches of scaly eczema are not infrequently met on or near the wrists. Eczema papulosum, however, is a form of eczema both common and obstinate which has a predilection for the limbs, both the arms and the legs, though it is met with on the trunk as well. Host forms of eczema are characterized by lesions with a more or less fluid exudation which loosens the superficial portion of the epidermis and spreads itself over the affected surface. In some cases of eczema, however, the tendency to exudation is lessened, and the probabil- ities are that it is less fluid in character, and under these circumstances does not gain the surface but collects at points beneath the epidermis, raising little solid projections which have received the name of papules. These may be somewhat closely aggregated, or there may be an appreciable distance between them, and the surface will be dry unless the pruritus leads to scratching and the edges of the papules are torn; in that case a small quantity of lymph may exude and dry into minute scales. In the course of time, however, the papules themselves tend to subside, and we have a surface somewhat glossy and scaly, but not to the extent usually seen in other varieties of eczema. This papular form of eczema has its seats of election. It is perhaps never seen on the scalp and some other parts, but it is quite common on the arms and forearms, thighs, and legs, especially their flexor aspects (Piffard). Eczema fissum is still another variety of eczema in which we have neither vesicles, pustules, nor papules, nor the extensive exfoliation which characterizes the exfoliative form of this disease. We may have a more or less reddened surface, but instead of the lesions already mentioned we find small cracks or fissures extending through the stratum corneum and sometimes through the stratum Malpighii as well. The exudation in this fissured variety is slight, crusting is slight, and after a time the skin returns to the normal condition by a simple closing of the fissures and disappearance of the congestion. These fissures are perhaps more frequently met with behind the ears, on the palms and soles, and at the various flexures (Piffard). Erythema multiforme is the next disease under the head of cutaneous inflammations which claims our attention, on account of its frequent appearance on the forearms. Gottheil defines it as an acute inflammatory disease, characterized by the appear- ance of reddish papules, tubercles, vesicles, or blebs of symmetrical distribution, and affecting by prefer- ence the backs of the hands and the feet. Elliot remarks that it is one of the most striking and con- stant features of erythema multiforme that almost invariably the lesions appear first on the backs of the hands and extend to the forearms and then to the lateral portion of (he neck ami face. Frequently simultaneously, but more often later than on the hands, the eruption is manifested on the dorsum of the feet and on the anterior aspect of the legs. It is frequently absent altogether from these regions, and besidesl the eruption will present much variation in individua cases. The eruption is always symmetrical, without, however, presenting absolute symmetry. Often one side of the body will be more severely affected than the other. Its symptoms, course, and the differential diagnosis are described by Gottheil as follows: After a prodromal period marked by a moderate febrile movement there appear on the backs of the hands and feet, or on the palms and soles, and more rarely on other parts of the body, a varying number of slightly elevated, firm, reddish-violet papules fading on pressure. This condition is known as erythema papulatum. In a few days the papules grow into tubercles perhaps one-third of an inch in size (ery- t hema tuberculatum). The centers then begin to flat- ten and fade out and assume a characteristic bluish-red hue (erythema annulare). At the periphery where the eruption is extending, the lesions preserve their elevated form and reddish tint. Adjacent patches may coalesce and form irregular figures, known as erythema gyratum and erythema figuratum. More rarely the appearance of blebs gives us the form known as erythema bullosum. Herpes iris is the designation given to a vesicular form of this erythema in which new concentric rings of papulovesicles appear in the depressed purplish center of an annular erythema. These various forms, often looked upon as distinct diseases, are in reality merely stages of the same process with varying amounts of exudation. A case may go through several of them and even show them simultaneously, for multiformity is charac- teristic of the disease; but usually one type only is present, and the commonest by far is the papular one. The malady occurs especially in the spring and fall, and lasts for from four to six weeks. It happens at any age, and issomewhat more frequent in females than in males. The mucosa? are occasion- ally affected. It is prone to relapse, and usually re- aopears in its original type. It is occasionally com- plicated with purpura, acute articular rheumatism, and endocarditis. Its typical course and location, the papules or tubercles whose red color is removable on pressure, and the absence of desquamation are sufficient to characterize the disease. An eczema has exudations, scales, and crusts, and itches intensely. Urticaria has papules or pinkish, fugacious elevations, with much itching and reflex irritability of the skin. A papular syphiloderm is copper colored and not removable by pressure; the palms and soles are usually involved, and other syphilitic symptoms are generally present. Prurigo has deep-seated, colorless pap! begins in childhood, and itches intensely. Tri- chophytosis corporis is scaly in the center, and the parasite can usually be readily found. While the arms are one of the rarer sites for the vesicular eruption of herpes zoster, yet the fact should be borne in mind that this disease occasionally manifests itself in the course of the brachial nerves. Its characteristic symptoms should make the diagno- sis in most cases easy. Its symptomatology is this: The eruption is almost regularly preceded by distinct premonitory symptoms, consisting mainly in neuralgio pains of variable degrees of severity over the area about to be affected and lasting from a few hours to several days, occasionally even for weeks. Some- times they are missing entirely, particularly in young children. The pain may be of a diffuse character, or, again, confined to certain points which correspond anatomically to the underlying nerves and their ramifications. The cutaneous phenomena make their appearance always in an acute manner. At first there are redness and slight swelling over the diseased area. This is soon followed by groups "f small papular elevations, which in the course of a few hours are transformed into vesicles from the size of a 511 REFERENCE IIAXDROOK OF THE MEDICAL SCIENCES Arm and Forearm, Diseases and Injuries v peripheral extension, become confluent go as to form larger bulla-. They have generally little dency to burst, and do so only accidentally. Occasionally a larger surface may be uniformly stud- .1 with these vesicles, but as a rule there are several distinct and isolated groups of them, varying in size from a dime to the palm of the hand, of irregular tiape, and arranged more or less exactly in the form i simigirdle when situated on the trunk. In other regions the unilateral distribution of the eruption ig the course of one or several cutaneous nerves forms a striking feature. These groups Come Out icessively, the one nearest the spinal column Usually appearing first, but all the vesicles constituting pat cli are formed and run their course contem- poraneously. Their contents remain clear for three or four days, then become gradually more turbid, puriform, and by and by dry out, forming brownish crusts which finally fall off and leave in their place reddish or bluish discolorations. These persist for .■■ time and gradually fade away. In some instances, however, permanent marks may remain, which, by their arrangement and distribution, are quite characteristic of the preceding eruption. The time consumed for the completion of the cycle in each individual group is from eight to ten days, but through the successive appearance of fresh crops of vesicles n the older ones have almost reached the point of involution, the whole process may last up to four or even six weeks. The subjective symptoms which accompany the eruption are very variable. While in some cases the preliminary neuralgia ceases with the advent of the cutaneous manifestations, it is more often present during the whole duration of the disease, and is intensified by a burning and smarting sensation with which every new crop of lesions is ushered in. Some patients complain very little, others seem to suffer very much, particularly from nightly exacerbations which may disturb the sleep. Even after the com- pletion of the eruptive stage there may remain for some weeks, and occasionally for a long period, dis- turbances in the sensory functions of the affected area. Fever is frequently present with the zoster, but is rarely of much consequence. A very remark- able fact in regard to zoster is that it attacks a person only once during a lifetime. Exceptions to this are - few and far between that they do not materially affect the generally accepted law. The termination of the local manifestations does not always indicate a complete restoration in the affected territory- Not only may neuralgic pains persist for some time and become the source of agonizing at- tacks which deteriorate the patient's health, but in ie cases there remain pruritus, hyperesthesia, or complete anethesia and analgesia. Of particular interest is the so-called " anesthesia dolorosa," which occasionally follows a zoster. An explanation for this peculiar phenomenon may be found in that the pathological changes in the course of the nerve disturb the transmission of sensation from the surface to the center, whereby the anesthesia is produced, while the use of the pain is located in the sensory root of the spinal column. U though zoster is generally attributed to disturb- ances in the sensory nerves, the strange fact must be recorded that often muscular atrophy and motor paralysis are caused by it. Paralysis of the arm muscles after zoster brachialis has been noted by Schwimmer, Joffroy, Broadbent, and Gibney. The characteristics of zoster are usually so marked that little difficulty can exist in recognizing it. Its unilateral distribution along the course of well- inown cutaneous nerves, the successive appearance Vol. I.— 35 of groups of vesicles, their cyclic course, and the con- comitant neuralgia will easily establish the diagnosis. From eczema it is readily differentiated by the larger size of its vesicles and their tendency to pel i-t as such, whereas in the former they burst very won and give rise to characteristic oozing (Zei sler). Psoriasis is a disease which on account, of its customary distribution merits a description among the cutaneous affections of the arm. The lesion of psoriasis are characterized by the formation of a thick imbricated covering of dry scales of a light yellow, pearly white, or silvery color situated on a reddish, slightly elevated, well-defined base. The disease appears without premonitory symptoms, and the first indication of its presence is the appearance of small pin-head sized, rose-colored spots, w Inch in a day or 1 wo become! covered with silvery scales, psoriasis punctata. These spots increase at the periphery, while the scales become piled up into thick crusts which, from their resemblance to drops of mortar spattered on the skin, constitute the form known as psoriasis guttata. If the attack runs an acute course, the patches rapidly increase in size, and in a week may attain the dimensions of coins, psoriasis num- mularis. Generally, however, the eruption is noted for its chronicity, and months are required for this development. The tendency of the psoriatic lesion is to disappear of its own accord, although the time occupied in this process may be months or years. The activity of the scaly proliferation first begins to subside in the middle of the patch, which finally goes on to complete resolution, leaving a ring-shaped margin standing out in bold relief — psoriasis annu- laris. If the disease continues to extend, the rings meet, giving figure-of-eight-shaped eruptions, and as the healing proceeds, the point of contiguity in turn disappears, leaving irregular or serpentine lines — psoriasis gyrata. The accumulation of scales, which is the most distinct feature of psoriasis, varies in different cases as well as on different parts of the body of the same individual. On the scalp the scales are thick, and the eruption tends to extend beyond the margin of the hair. On the extensor surface of the limbs, also, the scales become piled up on elevated bases to the height of several lines. On the face and penis the scales are less abundant. Although the scales are adherent to each other and to the base underneath, yet they may be detached by the finger nail, when, if the disease is of recent origin, a pale reddish surface, which readily bleeds and is but slightly raised above the surrounding skin, will be seen. In cases of long standing the base is of a dark or venous hue and markedly thicker than the normal skin. The scales thus removed are quickly renewed and in a few days attain their former thickness. There is no discharge or moisture connected with the eruption at any time, and the sensation of itching may or may not be present. Although all parts of the body may be involved, yet there are regions of predilection which are generally involved, especially at the onset of the disease. These are the points of the elbows and the anterior aspect of the legs just below the patella?. The scalp is also a favorite position, and in typical cases the disease is more marked on the extensor than on the soft, flexor surfaces of the body. In all cases the eruption tends to symmetrical distribution. Although psoriasis is usually a well-defined disease and easily recognized, yet it is subject to variations and in atypical cases may baffle the skilled diagnosti- cian. In appearance it varies from a simple furfura- ceous desquamation which may be the result of fric- tion, to a veritable inflammation as in scaly eczema. Eczema squamosum, however, is less frequently symmetrical, the flexor surfaces of the joints are favorite positions, while the extensor surfaces of the points of the elbows or knees are not affected as in 545 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES psoriasis. In psoriasis the eruption is sharply de- fined, and its margins frequently stand out like a bold headland, while in eczema the patch is thickest at the center and its margin merges gradually into the healthy skin. A history of moisture will often enable one to decide, for eczema at its outset is always moist, while psoriasis is essentially a dry-eruption from the beginning. In eczema the accumulation of scales is less than in psoriasis, and they are of a bluish color rather than white. The scales in eczema are more easily detached, and the base when scraped be- comes bathed with serous exudation and does not bleed as in psoriasis. Eczema of the palms and soles is more common than psoriasis in this position. It is more fissured and may be the only part involved, while psoriasis does not attack these parts alone. The nails are affected in both diseases, but in eczema they are usually all affected at once, while in psoriasis one or more nails, but never all, are involved at the same time. Lichen planus and lichen ruber may be mistaken for psoriasis when the former are of long duration. Lichen first appears in the form of small pin-head to split-pea sized, flat-topped papules which are distributed in clusters and extending at the peri- phery run together, giving the eruption the appearance of one continuous patch, not unlike psoriasis; lint there is less scaling in lichen and the eruption extends by the formation of characteristic islets which may be seen on the outskirts of the original cluster. The characteristic position of lichen is on the flexor aspect of the wrist, a position seldom occupied in psoriasis. Syphiloderma squamosum often resembles psoriasis very closely, and next to eczema is most liable to be mistaken for this disease. On account of the close similarity, this form of syphilodcrm was formerly called syphilitic psoriasis. But syphilis attacks the mucous surfaces as well as the skin, and is seldom present on the latter without appearing on the former; while psoriasis never attacks the mucous membranes. Syphilis but rarely occurs on the el- bows and knees, but it is very commonly met with on the palms of the hands and the soles of the feet. One hand may be affected in psoriasis, while both are usually involved in syphilis. The erup- tion in syphilis is polymorphous, presenting from time to time papules, pustules, and moist condy- lomata which would at once enable one to distinguish it from psoriasis. In late syphilis the destructive nature of the disease will become apparent by scars or fissures, while psoriasis leaves no mark behind. The scales in syphilis are muddy gray, and the base of the eruption is more infiltrated and of a darker color; moreover, the history of the disease should always be considered (Corlett). Dehmatttis venenata is seen more frequently, per- haps, on the wrists and forearms than on other parts of the body, for the simple reason that these parts of the body are those most frequently exposed to tin' irritating influences which occasion the affection. Surgeons and obstetricians are frequent sufferers from a mild form of this difficulty, due to the application to their hands of strong disinfecting solutions. In this case, the prompt sequence of the symptoms, namely burning, swelling of the skin, redness, and occasionally the development of vesicles, upon the application of the disinfectant render the diagnosis easy and unmistakable. Workers in brass and copper, those whose occupation brings them into frequent contact with aniline dyes and other chem- icals, and operatives engaged in handling gummy and adhesive substances which have to be removed with st long soaps or with special chemicals, present similar lesions which are grouped by the dermatolo- gists under this same head. In many cases the skin of the hands will escape, while that of the wrists and forearms is more susceptible to the causal irritant. In all cases of dermatitis affecting exclusively or preponderatingly the wrists and forearms, the occupation of the patient and the opportunities for special exposure to specific irritants should carefully be considered in the diagnosis. Deep-seated Inflammations of the Skin. — The in- flammatory diseases we have so far reviewed are classified in the nosological scheme of Jessner as inflammations of the corium and subcutis. Of the deep-seated inflammations which constitute the next category, there is an affection classed by some as a form of erythema multiforme, and by others as a distinct disease, known as erythema nodosum which while it does not often locate itself on the arms, might yet prove puzzling to one unacquainted with its course if met, as occasionally occurs, exclusively in that locality. Its prodromal symptoms are practic- ally identical with those preceding an attack of ery- thema multiforme (q.v.), namely, fever, gastric dis- turbances, and pains in the joints. It attacks like- wise a similar class of patients, young people in a condition of depressed vitality. Its lesions are an exaggeration of those of erythema multiforme, but its customary distribution is less frequently upon the forearms. One of its alternate names, dermatitis contusiformis, is descriptive of the appearance of its lesions. The eruption appears in nodes of a con- siderable elevation, rounded or oval in shape, varying in size from that of a nut to that of an egg. They are warm to the touch, surrounded by an edematous area, painless, but tender to pressure. Their color is at first a rosy red, changing to a darker and more livid hue, and not removable by pressure. They never coalesce nor suppurate. In the course of eight or ten days they gradually disappear, going through the color changes that are seen in blood extravasa- tions and leaving a dark discoloration behind. Three or four nodes only are usually present, and their number rarely exceeds a dozen. Though the indi- vidual lesions last only a few days, a succession of fresh ones often prolongs the malady for two or three weeks. Recurrences are rare. Ordinary contusions may be mistaken for the nodes of erythema nodosum, but they never have the peculiar rosy color, are not usually multiple, are not round, there are no general symptoms, and there is the history of an injury. Syphilitic gummata may resemble them closely, but the antecedent pains are much severer. They are slower in their course, are very rarely seen in the young, and are almost always accompanied by other symptoms of lues, past or present. The prognosis is generally good, though complications may arise which may make the prog- nosis more serious. It may be stated as a general proposition that there is but little tendency for the cutaneous lesions of syphilis to localize themselves upon the arms and forearms. Particularly is this true of the earlier macular and papular eruptions, which have as a pathological distinction the involvement of the superficial anatomical elements of the skin and a generalized distribution all over the body; in which distribution, indeed, the arms are not exempt. An occasional tendency toward characteristic localization upon the arms is manifested in some of the later syphilides, whose characteristics are an involvemi of the deeper cutaneous structures and a less general and less symmetrical distribution over the body. Accordingly we see in some of the pustular syphilidea a certain very limited tendency to a location of the lesions on the arm, or what is more frequent, a tend- ency to aggravation on the arms of a pustular erup- tion elsewhere present in a milder degree. Thus an acneiform or impetiginous syphilide upon the and the trunk may be accompanied with an ecthy- matous, exulcerated syphilide of the arms. It is also to be regarded as somewhat characteristic of syphilis that an acneiform eruption should make its appearance upon the arms in portions so ill supplied 546 ];i:ii:i;i.N('i: handbook of tih: mi.dk \i. si if.jtceS Arm and Forearm, and Injuries Diseases of With BebaceOUS glands anil hair follicles as to be ordinarily exempt from the manifestations of acne vulgaris. ill,, occasional development on an arm or forearm of the later tubercular or gummatous syphilides can hardly he regarded as more than an accident to which any part of the skin of the body is liable in this protean disease, and withal the arms and forearms seem rather exempt than otherwise from any considerable frequency of accidents of the kind. Farcy. — There is one disease which presents, among its other lesions a form of deep-seated inflammation of the skin, whose pathological importance is very t though the disease itself is not at all common. namely, farcy, a name given to the lesions of (jlami. rs when they affect portions of the body other than the respiratory organs. The gravity of the disease, with a mortality estimated at upwards of seventy-five per cent., the comparative rarity of the affection, making it unfamiliar to most practitioners, and its tsional appearance on the arms as a result of infection of the hands, are the reasons which lead ine to include in this article a description which it is will suffice to make possible its recognition. The course of farcy or glanders includes a stage of incubation, varying from two to fifteen days, a premonitory stasre, consisting of ordinary pyrexia, febrile excitement, etc., and including pain affecting the muscles, simulating rheumatism, and sooner or later a <;a>_'e of eruption, which develops the specific characters of the disease. In acute cases the stage of eruption appears almost at once, or soon after the invasion, but in the more chronic cases there may be an interval of weeks. The most prominent of the local symptoms is the glanders eruption, consisting of a crop of pustules, remarkably hard, simulating those of small-pox, and attacking the skin like an exanthem. Virchow their development as follows: At first there appear some red spots which are very small and resemble flea-bites, these soon acquire a papular elevation, subsequently rising above the level of the ice like small shot, assuming a yellow color. These shot-like nodules are either flat or round, and they do not lie in a bladder-like elevation of the epidermis, but in a kind of hole in the corium, as is the latter had been punched out; they are not always solitary, but are often disposed in groups. There if • surrounding injection, and under the epidermis there is found a puriform and yellow fluid, seemingly homogeneous, which is formed chiefly from softening of the nodule. These nodules attack in a similar manner the mucous membrane of the nose, where they are .-mall and linseed-shaped, and give rise to the peculiar nasal discharge. Softening of these tubercles next ensues, the skin gives way and ulcera- tion follows, and thus are formed small holes filled with debris, producing the pus of glanders and the farcy abscesses. These tubercles may r be developed in other situa- tions, such as in the subcutaneous cellular tissue, producing circumscribed, hard and painful boils, or diffused swellings of great extent, which either open spontaneously, or give rise to extensive sloughing of the skin and deeper structures. In rarer instances the tubercles subside and reappear in other parts, a form of the disease which is termed "flying farcy." npanying the eruption are found small, soft tumors about the extremities, forming a kind of pyemic abscesses, generally seated in the muscle-. seldom attacking the glands, and, when subcutaneous, remarkably defined, like an egg. In acute farcy, which is generally induced by the inoculation of a scratch or an abrasion, there is the superaddition of inflamed absorbents and lymphatics, and in these cases we have diffuse suppuration of the limb and suppurating glands. In chronic farcy the wound degenerates into a fotd ulcer, and the inflammation and suppuration of the lymphatics is slow and tedious. This form often terminates in acute glanders. Traumatic .1 of the Skin. — It should be borne in mind that the forearms and bands are the portion of the anatomy nio-t accessible to ; neurotic patients who, for purposes of exciting sympathy or from oilier morbid impulses, indie their own person various lesions, rarely severe, yet occasionally difficult of diagnosis. Such lesions are ordinarily such as would result from the application of irritant or vesicant drugs, or such lesions as would result from prolonged mechanical irritation with the finger tips, the nails, or some rough or sharp instrument. In considering the traumatic affections of the cutaneous tissues of the arm and forearm, two forms of injury present themselves as of special frequency and importance, owing to the exposure of the upper extremity to all manner of vicissitudes incident to active life. These are extensive abrasions and extensive burns. The treatment of burns and abrasions of the upper extremity does not differ essentially from the treatment of similar conditions elsewhere, only on the forearm an extensive burn may do more damage than elsewhere on account of the subsequent contraction which may involve the subcutaneous tissues and compromise more or less seriously the independent action of the muscles which move the hands and fingers. On this account skin grafting according to the method of Thiersch is indicated for a burn on the forearm many times when a burn of like extent and equal depth, if situated else- where on the body-, might be left to granulate with impunity. As stated above, it has been my aim in considering the cutaneous diseases liable to affect the arm and fore- arm, to present such a picture of the lesion as would suffice for its identification. Further discussion of the pathology, etiology, prognosis, and treatment of the different diseases enumerated must be sought in other parts of this work, or in treatises more espe- cially concerning themselves with dermatology. II. Affections of the Fascia. The affections to which the fascia? and cellular tissue of the arm and forearm are liable are of three general types: erysipelatous, tuberculous, and syphil- itic. To these we may add certain rare cases of con- traction of the fascia antibrachialis, more or less analogous to Dupuytren's contraction of the palmar fascia, and of an equally uncertain pathology. Streptococcic Invasion of the Fascia. — Erysipelas is usually described as an affection of the integument, and the process is undoubtedly frequently confined to the skin, proceeding with its characteristic red blush to extend in the direction of the lymphatic current until the energy of the infecting streptococcic colonies is exhausted, and the disease subsides after a definite run of from six to fourteen days. This form of simple cutaneous erysipelas occurs with greatest frequency 7 upon the face, but may make its appearance anywhere on the integument where streptococci may find an entrance, through an abrasion, perhaps extremely minute, or may have found lodgment in the glands or follicles of the unbroken skin. Identical with cutaneous erysipelas in etiology 7 , but differentiated from it in course and sy T mptoms, is streptococcic invasion of the fascial and connective- tissue planes of the extremities and occasionally of the head and trunk. On account of the difficulty of access to the subcutaneous tissues through the un- broken skin, the history of fascial and cellular ery- sipelas will generally reveal a preexisting, probably bad-behaving wound on the distal side of the focus of the phlegmonous process. The liability of the fingers 547 Ann and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES and hands to traumatisms small and great, and the exposure of these parts to subsequent infection, ex- plain the great frequency with which fascial phleg- mons are met with on the arms and forearms, par- ticularly of mechanics. The "differentiation between the several types of fascial infection is not in all cases easy from clinical symptoms alone, but the behavior of typical cases is sufficiently characteristic to permit a probable diagno- sis, to which a bacteriological examination will in most cases add confirmation. Although mixed infec- tions doubtless often occur, other more strictly pyo- genic, infections rarely confine themselves to definite anatomical layers as do infections by streptococci. The course of streptococcic invasion of the fascia and cellu- lar tissue is accompanied by an amount of fever in general commensurate with the extent to which the lymphatic channels are opened up for the absorption of the products of the germ life, rather than com- mensurate with the mere extent of territory involved. The temperature reaction in cases of infection of the fascial and cellular tissue of the forearm is rarely very great, it being rare to witness a temperature higher than 102° to 102.5° F. when the trouble is con- fined to the fascia and connective tissue of the arm. In marked contrast to this is the course of the strep- tococcic invasion of the pelvic tissues, where the abundant lymph channels allow the absorption of enormous quantities of toxins and even pus. A similar difference is seen in erysipelatous infection of the arm and forearm when along with the infection of the fascia and cellular connective tissue there is like- wise an invasion of the skin itself, phlegmonous erysipelas, stricto sensu, where the general vascularity of the tissue allows a much more active inflammatory reaction to the microbial invasion. For this reason the temperature is a much less fallacious guide to the gravity of the condition in this than in many other surgical diseases. The onset of the disorder is usually marked with sensations of chilliness if not with posi- tive rigors, and a general malaise, anorexia, and more or less gastric disturbances are pretty constant ac- companiments of at least the early course of any ex- tensive affection of the kind. The amount of pain is very variable, and is for the most part decidedly less than one would expect to meet in a staphylococcic in- vasion of equal extent. This difference is due largely to the different anatomical tissues for which the two kinds of germs seem to have an affinity. Staphylo- cocci tend to form circumscribed colonies in the more vascular structures, often beneath tough and resis- tant connective-tissue planes, where the resultant pus or exudation gives rise to great and painful pressure upon the sensitive nerve fibers. Besides which it is very probable that the toxins produced by the staphy- lococci, particularly the staphylococcus aureus, are themselves peculiarly irritating to sensitive nerve tissue. The streptococcus, on the other hand, has a pre- dilection for the connective tissues and for the fascial membranes themselves, invading by preference their superficial surface; the resultant pus is not bound down beneath the tough and resistant membranes, and does not cause so much pain from pressure under confinement, and it is perhaps probable that the specific toxins of the streptococcus are somewhat less highly irritating to the sensitive nerves. The hu- man system, furthermore, seems to combat the streptococcus by a more ready manufacture of an- titoxin than it does in its efforts to overcome the staphylococcus, and thus to establish a temporary partial immunity to the attack of the streptococcus. This will account for the tendency that is sometimes manifested in streptococcic processes to linger on in a mitigated yet protracted manner, continuing to vegetate in the tissues in an obstinate yet less virulent form than at the outset of the attack. Thisis partic- ularly prone to be the case in cases of extensive in- volvement of tissues of low vascularity. The vitality of the germs permits their continuous growth in tissues of feeble resisting-powers, while the system, through the accumulated stores of antitoxin, can so far neutral- ize the toxic products of the bacterial growth that the materials absorbed do not poison the body, as is shown by the diminished fever and the general sub- sidence of general constitutional symptoms, in spite of the lingering of the local process in the fascial layers. Thus arises a prolonged, quasi-chronic form of the trouble, which is particularly likely to supervene when the fascial planes of the extremities are invaded. The streptococcic invasion of the fascial planes of the arm and forearm is generally first along the deep fascia, with or without concomitant involve- ment of the superficial fascia and the skin. Only when the process has been for some time under way do the muscular septa become involved, and then a most formidable condition known as a deep dissecting phlegmon results. The systemic effects have already been mentioned above. The local symptoms are characteristic in typical cases, and allow a ready diagnosis. At a point, it may be bordering on a wound, but more fre- quently at a greater or less distance to the proximal side of it, the skin will be seen to have a somewhat livid hue, and will appear somewhat edematous; yet there will be lacking the dense infiltration of all the tissue layers which characterizes a general cellulitis depending upon infection with the staphylococcus. Then, too, the classical signs of inflammatory action will be less marked, unless the skin and superficial fascia are also involved — i.e. there will be, as coin- pared with the staphylococcic infection, less redness, less swelling, less heat, and less pain. The original wound may or may not appear to be involved in the infection, or if the wound is itself the seat of suppura- tion, the channel of communication between the original wound and the seat of the secondary suppura- tive process may be difficult to trace. The limit of the involved area is very indistinct, as, owing to the want of vascularity of the affected tissues, there is no marked inflammatory induration acting as a wall of circumvallation about the focus of infection. To the examining finger, the sensation imparted on palpation is rather that of a layer of fluid separating the tissues, than that of a localized abscess with indurated borders and softening center. When the skin and superficial fascia are also in- volved, which is the exception rather than the rule, the implication of these more vascular structures in the morbid process will lend the appearance of a more acutely inflammatory type to the disease. The redness will be that of the angry blush of cutaneous erysipelas. The inflammatory exudation into the interstices of the skin will afford a more marked swelling, and a brawny feel to the tissues on palpa- tion. The epidermis may be lifted in more or less extensive vesicles or blebs, whose original serous con- tents may become sanguinolent, and the delimitation of the focus of infection may be more distinct, the deep fascia being rarely involved in these cases much beyond the cutaneous blush. The disease, if untreated or if refractory to treat- ment, though it tends to recovery through exhaustion of the virulence of the infecting germ, yet is likely to be extremely destructive to the tissues which it at- tacks; and if the accumulating pus is not freely evac- uated, the process, although residing by preference in the layers of connective tissue first attacked, yet can easily transgress these limits and by the erosive and solvent action of the pus, or by the progressive outgrowth of the streptococci, involve contiguous structures to an extent that may be dangerous to life through secondary hemorrhage, due to erosion of an artery, or from pyemia, due to septic thrombosis in the veins followed by "yellow softening" of the clot and embolism. 548 REFERENCE IIAXDROOK OF THE MEDICAL SCI] Ml S Ann ami Forearm, Diseases ami Injuries <>f The prognosis, in the forms affecting the fascia alone is good, if opportunity is given for a free hand in the surgical treatment of the case, ami the patient has a certain strength of constitution behind him. In the form mine strictly known as phlegmonous erysipelas -i.e. the form complicated by the involve- ment of the skin and superficial fascia as well the ignosis is grave if any considerable portion of the limit is involved. In that form of the disease in which the deeper eonneet ive-t issue planes are involved — i.e. the intramuscular sepia and the perimysium — while the prognosis as to life is fair, the prognosis as to restoration of the limb, or even as to life without ificing the limb, is uncertain. The diagnosis of typical cases is not difficult, the non-involvement of the adjoining structures being more or less readily appreciable ami characteristic. ipelatous infection of the fascia is to be differ- iicd from the general inflammatory edema ounding a focus of deep-seated suppuration, from malignant edema, and from the tuberculous and syphilitic forms of connective-tissue disease. The ol differentiation from deep-seated and destructive abscess of staphylococcic origin have been ribed above. They are non-involvement of the , or its involvement under a strictly erysipelatous type of inflammation with the characteristic blush; 01 1 1 ci i ion of blebs and superficial infiltration and thickening of the skin itself, quite different from the brawniness accompanying the infiltration of the ler la vers, which is characteristic of a deep ess. Furthermore, there is wanting in this form ■ lamination the delimiting wall of inflammatory exudate which marks ordinary abscess formation, no distinct line of demarcation separates the ted from the healthy tissue. From malignant edema an erysipelatous infection of the fascial planes is likewise to be differentiated by the less malignant and acute character of the disease; by the absence of the extreme fetor accompanying lesion, and by its tendency to confine itself to kind or to one layer of tissue. Malignant edema is a rare disease in man, and, according to Park, is ntially a specific form of gangrene. The infected moreover, frequently contains gas. From the tuberculous form of the disease, the erysipelatous form is to be distinguished by- its rather prompt following upon a wound on the distal side of the phlegmon (two to twelve days'), by its rather rapid rise to an acme (four to six days), by distinct evidences of sepsis rather than cachexia, by the character of the evacuated discharge (more distinctly purulent and often containing more or less extensive sloughs), and by the pain and heat, which are much mure distinct than in the cold abscess. From syphilis of the fascia, an erysipelatous process can be distinguished by the absence of the gummatous infiltration, by the fever and pain, by the sudden onset often consecutive to a lesion on the distal side of the phlegmon, and by the absence of other manifesta- tions of syphilis. It must, however, be borne in mind that a syphilitic subject may. quite as readily as any other, become the subject likewise of a non- syphilitic infection of the fascia. The treatment of erysipelatous disease of the fascia consists in giving the freest possible vent to the pus, in vigorous local antisepsis, and in stimulating and supporting the general system. Further means to ider in combating this formidable malady are the cautious use of either active hyperemia (induced by the local hot-air bath) or passive hyperemia (induced by a constricting bandage on the proximal side of the lesion), the introduction into the circulation of certain general antiseptics such as soluble silver or some formaldehyde derivatives, the use of specific antitoxic sera, and the use of specific, autogenous bacterial vaccines. As long as the disease is confined to the deep fascia, we may expect by free incision and by the local application of antiseptics to arresl the infectious process. Incisions to this end should be made subject to these rules: They should be parallel lo the long axis of the limb; they should penetrate down lo, but not beyond, the deep fascia; and they should be numerous enough and long enough to give ' access to all demonstrably affected tissue. With these rules in mind the surgeon -in mid and may Inci e the tissues freely and extensively, and may do so without great danger either of provoking extensive hemorrhage or of exposing the patient to sloughing of t he -kin, or to n lore extensive gangrene of the extrem- ities, as the main blood-vessels run beneath the deep fascia, and the cutaneous branches are fully as likely to have been already obliterated by the -optic process as they are to be divided by the knife. It is well to avoid the large superficial venous trunks of the forearm, and particular pains should be taken to avoid the mediana profunda vein at the angle of divergence of the median basilic and median cephalic veins, as this is the main communicating branch between the deep and superficial sets of blood-vessels, and by extension along this vein a thrombus might communicate the septic process to the deeper tissues. After free incisions have been made, there comes up the question of whether or not it is best to use the curette. This is generally to be answered pretty decidedly in the negative. The introduction of the curette, even of the rinsing curette, into the crevices between the deep fascia and the skin, where the infectious process is mainly located, can hardly serve to dislodge septic material spread over a large area to any such degree of thoroughness as will compensate for the disadvantages attending the mechanical lifting of one anatomical layer off the other, for by means of this disturbance of the anatomical layers the infecting germs are given more ready access to still uninvaded regions. The case is quite different from that of a circumscribed abscess, where over a region of com- paratively small area necrotic tissue needs to be removed to a considerable depth. In fascial ery- sipelas a large area is affected to only a moderate depth; and weighing the results of the unavoidable trauma inflicted by the instrument, on the one hand, with the proportionate gain in the removal of septic material on the other hand, the balance will in most cases be against the use of the curette in septic fascial disease. Less damage is likely to ensue from the careful use of the probe in exploring the extent to which the puru- lent process may have undermined the skin; in fact, a careful exploration of this kind is indispensable to guide the surgeon in making his incisions. It is particularly necessary to make at least one incision at the proximal border of the suppurating area, so as to permit thorough flushing of the infected tract and to> establish through-and-fhrough drainage, and the upper limits of the suppuration can most conveniently be determined by the use of the probe. When once the limits of the disease have been determined and the necessary incisions have been made, a thorough flushing of the diseased area with antiseptic solutions should follow. To this end con- siderable hydrostatic pressure should be employed, and every effort should be made to force the fluid injected at one incision to escape at another. If this does not readily follow on introducing the tip of the irrigating-tube at one orifice, it is quite in order to> make a passage for the fluid by subcutaneous dissec- tion if necessary, either by dividing the obstructing tissue bands with the knife, or by forcing the tip of the glass irrigating-tube under the skin until the flow is established from one incision to another. A solution of mercuric chloride, 1 to 1,000, is frequently used for this purpose, and should be passed through the wounds in large quantities. Stronger solutions of this 549 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES same salt may be used; but if they are, a second flushing with plain water should follow on account of the poisonous qualities of the salt. Aside from its value as an antiseptic, certain mechanical advantages attend the use of hydrogen peroxide in septic infection of the fascial planes — namely, the liberated gas lifts apart the layers of tissue and opens up the diseased territory to the further action of the antiseptic, yet lifts the superficial layer very gently and evenly without carrying septic material into uninvaded areas. Furthermore, the development of the oxygen gas can be felt through the integument, and the bubbling of the gas may be sufficiently appreciable to the touch of the surgeon to act as an indicator of the presence of suppurating tracts, perhaps unsuspected from investigation with the probe alone. After free multiple incisions and thorough flushing, seton drains should be inserted, passing subcutane- ously from one incision to another; this is a far more useful form of drainage than the mere packing of the wound with gauze. In fact, distention of the pockets is to be avoided on account of the undesirable tension on the margins of the affected area where the process is likely to extend. It is essential to the usefulness of the seton that the incision through which it enters and that through which it emerges should be suffi- ciently ample so that the lips of the wound shall not hug tightly the material of which the seton is composed, otherwise the object both of the seton and of the in- cision is nullified. The object of the seton is strictly that of a wick, and this function is much better fulfilled by a slender seton, easily movable to and fro in its bed, than by a large mass of material which chokes the orifices of entrance and of exit and dis- tends the cavity which it meant to drain. The best material for a seton is sterilized absorbent lamp- wicking, or perhaps iodoform lamp-wicking. A good substitute for this is a ribbon of plain or iodo- form gauze, from one-half to one and a half inches wide, folded once or twice on itself. Either the seton should be threaded through the eye of a seton probe, or through the eye of the probe should be threaded a ligature of heavy silk and this loop be used as the carrier for the bulkier seton. After the incisions are made and the wound is flushed out, and the setons are drawn through, the question of dressings comes up. Just here it is necessary to suggest caution in the in- discriminate application of wet dressings. The ad- vantages in the use of wet dressings lie in the greater absorptive powers of the wet dressing by which the discharges are more readily withdrawn from the neighborhood of the wounds, and in the more efficient action of the antiseptics with which the dressings may be permeated. The dangers from wet dressings, however, are also twofold. First, they provoke a certain amount of maceration of the skin, by which erysipelatous dermatitis, an ever-threatening complication, is in- vited. Secondly, the relaxation and softening of the tissues, which is advantageous in relieving the stasis in the capillaries where more vascular structures are involved, may prove equally effective in furthering the spread of the streptococci along the planes of soft and comparatively non-vascular tissue which are involved in fascial phlegmons, allowing the process to extend in tracts which might otherwise be less vulnerable to their attack. In view of these two objections, I am convinced that wet dressings must be used with considerable caution in phlegmons whose principal seat is between the deep fascia and the skin, to avoid encouraging the extension rather than the arrest of the disease. The more free and complete the drainage, however, the less these objections hold, and where the incisions are ample and numerous, the obvious advantages of the wet dressings may more than counterbalance the 550 objections to them, to which attention has been called by way of caution. In any case the need of frequent renewal of the dress- ings is imperative. When it is impossible, through too great fatigue and pain to the patient, to redress the wound sufficiently often to make headway against the persistent suppuration, with the proviso that the incisions shall be sufficient in number and in extent, the constant drip or the constant bath may advan- tageously be substituted for the wet dressing. Inas- much, however, as the disease we are now considering affects principally non- vascular tissues, the great bene- fits which follow this form of treatment when another class of tissues is involved, are not so conspicuous in cases of purely fascial disease. In cases complicated by cutaneous erysipelas, the constant bath, however, will be found of great value. At subsequent dressings, after abundant provision has been made for the speedy discharge of pus, great advantage will be found in saturating the wicks which are drawn beneath the skin from incision to incision with Peruvian balsam, ichthyol, or some other tissue stimulant, and this use of stimulant dressings within the wound cavities will be found use- ful as long as these remain open. In the later stages of the disease when the active spread of the suppuration seems to have been arrested, much may be done to hasten the obliteration of the pockets beneath the skin and fascia by the skilful dis- position of compresses so as to cause a mechanical closure of the portions of undermined tissue which are farthest removed from the track of the setons. Similarly when, in the process of healing, the under- mined tissues have become once more agglutinated, with the exception of the tracks of the different setons, each seton track should be mechanically cut in half by the pressure of a compress, and be kept open only in that part which is near the incision. For this mechanical obliteration of parts of the undermined territory, tolerably firm bandaging of the limb is necessary. The constitutional treatment of erysipelatous disease of the fascia is simply that of the sepsis which always accompanies it, and consists in pushing nutri- tion, and stimulating the circulation, and maintaining the activity of the emunctories. We spoke above of the use of Bier's "hyperemia" in the treatment of phlegmonous erysipelas of the arm. The technique of "hyperemic treatment" must, how- ever, be fully understood before it is safe to apply this means to the treatment of the "type of difficulty we are now considering. For those who are less experienced in its application it is likely that "active hyperemia," induced by the local hot-air bath would present the safer proceeding. Those, on the other hand, who have had a certain experience in the use of the constricting bandage in the treatment of inflam- matory troubles in the extremities may find at lea-t two special advantages in this form of treatment; first, the constricting bandage will act in a way anal- ogous to its action in snake-bite, in that it will, for a while withhold from the general circulation con- siderable stores of virulent toxins, thus, for such time as the bandage is in place, protecting the heart and the nerve centers from their deleterious influence and, it is claimed, modifying and mollifying these toxins while locked up in the arm distal to the bandage so that they are rendered less pernicious when allowed to flow back into the general blood-mass, such periods of mechanical protection of the heart and nerve cen- ters being marked by a distinct remission in the fever; econdly, in a process tending as distinctly as does this to extensive sloughing and gangrene, the use of "obstructive hyperemia" (Stauungshyperilmie) it is claimed will decidedly promote the nutrition of the threatened parts, enabling them to withstand a decree of inflammation which, without this protective means, might lead to extensive local necrosis. For REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arm and Forearm, Diseases and Injuries of details of the technic demanded the article dealing with the subject of hyperemic treatment in general should be consulted. Since the demonstration of the presence of formal- dehyde or of its derivatives in most of the body Quids after the administration by the mouth of bexamethylentetramin, the use of this drug has been suggested in the treatment of septic conditions such as attend a phlegmonous erysipelas. French surgeons lay considerable stress on the advantages of intro- ducing by hypodermic; injection considerable quan- tities of solutions, or suspensions of the colloid metals, particularly colloid silver, into the circulation. I he condition we are considering would seem an appropriate one for this form of treatment. Antistreptococcus serum has not given the constant results which it was hoped that it would in combating ptococcal diseases. This is probably due to the immense variety in the attributes of the different "strains" of streptococci derived from different sources. If positive results are to be expected from the use of a streptococcus antitoxin this, it appears, must be a highly "polyvalent" antitoxin, derived from as large a number of different virulent sources as possible, in the hope that at least some of these sources may have characteristics nearly parallel to those of the particular "strain" of streptococcus which we are combating. The uncertainty of such a coincidence has caused the antitoxic sera to become less depended on than streptococcus vaccines in combating erysipelatous processes. While for many bacterial diseases the use of "stock vaccines" gives generally satisfactory results, the very reasons which make for the unreliability of antistreptococcus serum make it imperative that in streptococcus processes an "autogenous vaccine" should be used. In the intelligent use of autogenous vaccinal injections we have a potent weapon in combating phlegmonous erysipelas. Tuberculosis of the Fascia. — Primary tubercu- losis of the fascia is a somewhat rare disease, and is prone to show itself, as do tuberculous joint lesions, much more frequently on the lower extremities than on the upper. Given, however, a tuberculous joint lesion in the upper extremity, secondary involvement of the fascia is probably as frequent at one seat as at the other. Fascial tuberculosis differentiates itself from fascial disease of other kinds by all the charac- teristic signs of tuberculosis. The onset of primary fascial tuberculosis is generally comparatively painless in the absence of secondary infections, and it is rarely possible to trace its direct connection with a coexistent wound, for the reason that the development of the tubercle germ is so slow that the wound of ingress may long have healed and have been forgotten before any tuberculous process manifests itself. On the other hand, secondary involvement of the fascia, where tuberculous joint trouble is present, is generally of easy demonstration. Though streptococcic infection of the fascia may relapse into a chronic form, it does not begin insid- iously as does a tuberculous process, and though in the latter stages of a tuberculous fascial phlegmon when secondary infection has occurred, so much of a distinctly pyogenic type may have been stamped upon the process as to render difficult a diagnosis from the signs present, yet an accurate history of chronic, almost latent disease, present for a considerable number of days or weeks before the onset of acute symptoms, is entirely inconsistent with what we know of the behavior of the streptococci, and is almost pathognomonic of tuberculous infection. In the absence of an ingrafted secondary infection, the febrile reaction to tuberculous disease of the fascia is slight, and when the local process is not extensive the general constitutional reaction may be almost nil. The tendency to involve adjoining structures is not marked, the skin proving resistant for a long period to perioral inn ; on the other hand, the tendency to metastatic involvement at a distance is one of the most considerable perils attaching to the malady. The slight tendency of primary fascial tuberculo is to involve adjacent structures may be due to the slow growth of the tubercle bacillus giving an opportunity to the surrounding tissues to fortify themselves by a defensive leucocytic infiltration against the advance of the germ into more vascular, and consequently more resisting, fields. In this comparative vulner- ability of the fascia, and comparative invulnerability of the surrounding tissues lie at once the safeguard and the danger of this form of tuberculosis. So long as skin, joints, and tendon sheaths are not involved, the subjective symptoms and the impairment of function are so inconsiderable that the process may remain unrecognized, and radical measures for its extirpation may be postponed until great destruction of tissue has taken place beneath the integument, or until with the final involvement of the skin in the tuberculous process a mixed infection has become imminent, or has actually taken place. On the other hand, when attacked at an early stage the restriction of the disease to one tissue favors greatly the chances of its complete eradication by appropriate measures. The disease at first is confined to the surface of the fascia. There may be a small area affected, or it may be quite extensive. There is a lay r er of tubercu- lous granulation tissue which can be readily scraped off, leaving the protecting wall of inflammatory tissue which nature always throws round a tubercu- lous abscess. With the occurrence of secondary pyogenic infection, or with a primary seat in, or a later involvement of, the deeper intermuscular septa, the prognosis, which is otherwise pretty good, be- comes very much more grave both as to restoration of the function in the limb and as to life itself. This knowledge of the prospect ahead at once gives us the key to the proper treatment. The non- vascular nature of the tissue involved in fascial tuber- culosis diminishes very greatly the chances of a sponta- neous subsidence of the disease through the process of encapsulation and calcareous infiltration of the tuber- cles. Mechanical ablation of the affected tissue is the only hope of safety. Here, too, our knowledge of the natural history of the infecting agent will influence the technique of the operation. Whereas in cases of strep- tococcic invasion of the fascia it was advised to keep instruments out of the focus of infection, and to depend upon copious flushing with antiseptics and linear in- cisions with multiple drains, here the form of incision should be so varied as to allow the raising of large flaps whose under surface, as well as the beds upon which they rest, should be thoroughly scraped with the sharp spoon, or shorn with the edge of the knife, or better clipped with scissors curved on the flat. Sinu- ses involving the skin should receive still more radical treatment; they should, if possible, be resected through their whole extent. It may be well to point out that V-shaped flaps should be so cut as to have their apices away from the trunk in order to secure their sufficient blood- supply and to avoid sloughing. When secondary infection has not taken place, or does not seem to be virulent in character, drainage should be dispensed with as far as possible, as it is more than doubtful whether tubercle germs can be discharged from the system by mechanical drainage. If, on account of secondary pyogenic infection, it be considered necessary to make use of gauze drains, they should be few in number, should not be used to stuff the cavities, and above all should be peremp- torily withdrawn at the earliest possible moment. The use of a moderately tight bandage by mechanic- ally closing all "dead spaces" will in a large measure obviate the necessity for the use of drains, whose sole function it is to prevent the accumulation of wound secretions, but whose unfortunate attribute 551 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES it is, in many cases, by the irritation they cause as foreign bodies, to excite secretion from the tissues with which they lie in contact. A condition which would seem to demand a longer continuance of the drain, in reality indicates still more strongly a revision of the operation; indeed, in all cases of the kind, it is well for the surgeon to explain to the patient or to his friends, before undertaking operative measures, the possibility, or even probability, of further operation being required, and to get consent to necessary revis- ional operations at the beginning. The free use of iodoform within the wound is strongly to be recommended in tuberculous processes, with proper caution to avoid its toxic effects. Pow- dered iodoform should be rubbed into the curetted surfaces with the fingers so as to distribute this pre- eminent tuberculocide into the pockets and crevices of the infected cavity. For situations where the turning up of flaps is not possible, iodoform emulsion may be injected with a syringe. The studies of Beck, of Chicago, have demonstrated the great usefulness of bismuth paste in many surgi- cal tuberculous processes. This paste may be in- jected in cases of fascial involvement by puncture of the unbroken skin with a hollow needle. Where operation has laid open the diseased foci, after the thorough surgical treatment of the diseased area, bismuth paste may be applied in a thick layer on the under surface of the flaps, or it may be injected, after the wound is stitched, by a needle introduced be- tween the apposed lips of the wound in the interval between two sutures, so as to interpose a thick layer of the paste between the skin and the underlying muscles. As in other tuberculous processes, the use of tuberculin should be considered, both in establishing a diagnosis and as a means of treatment. It should be used according to established principles. Tuberculous processes affecting any of the structures of the extremities are particularly favorably situated for treatment by passive hyperemia. According to the recommendation of Bier, a lightly constricting bandage applied on the proximal side of the lesion, as near the trunk as may be, for from one to two hours daily has a favorable influence on most cases of local tuberculosis of the extremities and does not interfere with the use of other therapeutic means. Syphilis of the Fascia. — Syphilitic involvement of the fascia is almost always of one type — that of a gummatous deposit. This type of syphilitic lesion is one of the later manifestations of syphilis, and, except in the precocious or malignant type of the disease, is scarcely to be looked for until after the second year. A painless, though possibly tender subcutaneous tumor extending rather widely beneath the skin, without the characteristics of malignancy on the one hand, nor the encapsulation and lobulation of the lipoma or soft fibroma on the other hand, nor yet the fluidity of an advanced tuberculous or pyogenic pro- cess, will suggest the diagnosis of fascial gumma. When the gummy deposits have likewise invaded the skin proper, and secondary infection with pus germs has taken place, the differentiation between syphilis and tuberculosis of the fascia may be somewhat am- biguous. Incision into the mass will soon reveal the characteristic appearance of the gumma if the diagnosis be not already made. If still not made at the time of the incision, the exceedingly intractable character of the lesion under ordinary surgical treat- ment will suggest the diagnosis, especially when contrasted with its readiness to heal under antisep- tic treatment when this is combined with the exhi- bition of antisyphilitics. It has been well said that the whole responsibility of the surgeon is not discharged when a diagnosis of syphilis has been made, and gumma of the antibra- chial fascia is eminently a case in point. Although by stimulating the activity of the lymphatics with po- 552 tassium iodide, even an extensive gummatous de- posit may be eventually removed, yet the complete and speedy restoration of the arm is much better insured, especially when secondary pyogenic infection is present, by free incision and vigorous clearing away of the gumma with the rinsing curette, depending on the constitutional treatment to complete the cure. Contracture of the Antibrachial Fascia. — To the diseases of the fascia which have thus far been described must be added, for the sake of completeness, certain rare cases of contracture of the antibrachial fascia in which this membrane impedes the action of the mus- cles governing the hand by rendering the member a- it were "hidebound." Little or nothing is known of the pathology of this rare condition, except that it is sometimes seen as the sequel, either temporary or permanent, of other forms of fascial disease. The affection is sometimes seen, however, in a strictly progressive form without traceable antecedent dis- ease or injury. Steaming and massage would suggest themselves as the most promising means at hand for combating the difficulty, and A. Richet has recorded one case which yielded to potassium iodide, and was in con- sequence deemed to be of syphilitic origin. A certain number of cases, seemingly of this general character, are reported to have beenfavorably affected by the local injection of fibrolysin. III. Affections of the Bones, the Periosteum, and the Joints. (o) The Boiies. — Of the bones of the arm and fore- arm, the ulna or radius may be congenitally absent; in which case the remaining bone undergoes a compensatory hypertrophy, and this produce- a lateral curvature of the wrist away from the enlarged side. The bones may atrophy as a senile change or from disuse, especially in long-standing ankylosis, unre- duced dislocation, or paralysis, or their develop- ment may be arrested in the later stages of infantile paralysis. In achondroplasia the bones of the forearm often appear much thickened and curved. Rickets, as Park describes it, is a constitutional dystrophy caused by improper deposition of calca- reous material in the soft and somewhat perverted fetal cartilages. Pathologically it is marked both by a defect in the calcium content and also by the irreg- ular epiphyseal lines and excessive amount of vascular tissue. " On making a section through the end of the bone, one sees that instead of the two sides of the epiphyseal cartilage being parallel to each other, that next the diaphysis is quite irregular, there are islets of cartilage extending into the bone, the epiphyseal line is very much thickened and the ossification is very irregular" (Cheyne). The result is that at the epiphyseal lines one can feel a distinct enlargement, especially noticeable at the wrist, the lower end of the radius being as a rule the first part affected. Owing to the softening of the bony tissue, curves and deviations of the bones of the arms occur in severe cases in infancy, secondary to kyphosis of the spinal column, the child tending to assume a frog-like posi- tion to relieve the spine of the weight of his head and shoulders. In some instances fractures have been observed to occur in rickety bones on slight provoca- tion. The treatment is regulation of the diet and improvement in the hygienic conditions together with the administration of tonics. Phosphorus and the hypophosphites are especially recommended. Extract of the thymus gland has been shown to exert, in some cases, an appreciable effect in disorders of the osseous development. Its use in rickets has been recommended as a means of promoting the fixation of phosphorus in the bones, particularly of children. The radius is a common place for the commence- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ann and Fercarin, and Injuries Diseases of inellt of OSTEITIS DEFORMANS. Here (lie boneS enlarge and soften, and a distinct bowing is at time noticed, while from the irregular enlargement of the articular ends, the hand is often deflected. This disease, which is also known as Paget's disease of the bones, is a rare affection, appearing generally after middle age. The disease is essentially a symmetrica] one. The articular ends of the humerus and ulna may lie involved in the hypertrophy characteristic of uarie's disease or ostioarthropathie hypertrophiante lique. In senile atrophy, osteomalacia and osteopsathy- rosis, as also in rickets, in syringomyelia, and in metastatic deposits from malignant tumors, <-. <• of marked evidences of general sepsis, together with the presence of similar local signs. In the absence of pronounced suppuration, we are justified in pursuing longer, in this form of bone disease than in the other, our efforts to check the process by means of rest, coun- ter-irritation, fomentations, etc., but with the advent of signs pointing to pus formation, free incision and drainage are as positively indicated as before. The Joints. — The articulations of the upper ex- tremities are, like those elsewhere in the body, liable to dislocation; for discussions of which other portions of this work may be consulted. It will, however, be well to call attention here to a somewhat rare affec- tion of the elbow, occurring exclusively in infants and young children, resulting from forcible dragging on the forearm, often by the nurse, or in play. In this con- dition the forearm is held flexed in a prone or semi- prone position, and supination is very painful. The 554 REFERENCE HANDBOOK ON THE MEDICAL SCIENCES Ann and Forearm, Diseases ami Injuries of condition is probably one of subluxation of the radius ,1(H\ award, and the partial escape of its head from the grasp of the orbicular ligament; the normal laxity of the ligaments in childhood and the want of full devel- opment of the head of the radius contributing to make the condition possible. The signs may be re- moved by complete supination followed by flexion, under an anesthetic if necessary. The forearm should then be placed in a sling and massage and careful ex- ercise employed. Of the primary inflammations in these joints, SIMPLE synovitis is perhaps the most common. The acute form may be due to trauma or to overuse, and gives rise to pain on pressure or on movement of the joint, and to swelling due to an increase in the amount of synovial fluid, sometimes to an effusion of blood. A bulging tumor is formed where the joint capsule is thin; in the elbow joint the tumor is generally shown i riorly. Purulent infection of the effusion may take place. The treatment of simple synovitis consists in rest, enforced if necessary by fixation of the joint, pressure, by careful bandaging or by the wearing of a woven rub- ber sleeve, the application of cold or of heat, the latter best in the form of the local hot-air bath, and passive hyperemia. With the subsidence of acute symptoms, massage carefully regulated active and passive mo- tion of the joint are always helpful and are frequently indispensable. Active and passive motion, while they may be administered manually, are more easily regulated and are more efficaciously applied by means of the Zander mcchanotherapeutic machines. The chronic form of synovitis may date from a previous acute attack, or may be chronic from the start. The pain in this form is either small or absent. I luctuation can usually be elicited, while creaking on moving the joint may be quite a noticeable symptom. The treatment here, too, will consist in pressure, rest, massage, counter-irritation, etc. It is particularly in cases of chronic synovitis that the local hot-air bath together with active and passive motion accu- rately regulated by means of the Zander apparatus may be relied upon to give the best obtainable results. Tuberculosis of the joints is usually due to in- fection from the bone, though it may in some cases be primary in the synovial membrane. The usual symptoms are swelling, due to effusion and to the thickened capsule; there is always a limitation of motion, and usually pain, due to the friction of two roughened joint surfaces, and marked and painful spasms of the muscles surrounding the joint, while atrophy of these muscles is generally to be noted. Immobilization of the j<3int, together with extension, are indicated as in joint tuberculosis elsewhere. This is, however, difficult to achieve in the upper ex- tremity by any portable apparatus, though simple immobilization at the elbow and the wrist may be attained by proper splints. For thoroughly satis- factory extension, the use of the weight and pulley with recumbency in bed is essential, and even with these, satisfactory application of this form of treat- ment to the shoulder joint is very difficult, owing to the extreme mobility of the scapula. On account of the imperfection of methods of extension and im- mobilization in treating tuberculosis of the joints of the upper extremity, we turn the more readily to the use of iodoform emulsion and other substances by injection into the joint cavities, and in severe cases proceed to resection, typical or atypical. In conjunction with other methods, general tonic treat- ment should not be foregotten, including open-air living and the use of tuberculin. Acute suppurative arthritis is sometimes found, due to the infection from a wound, or of hematogen- ous origin. All the signs of a severe and acute inflam- mation are present. The treatment is in all cases by in- ei.sion and drainage and by immobilization of the joint. The value of bacterial vaccines and of pa ive hyperemia should not be overlooked in this formid- able and crippling disease. Ankylosis is often a result in spite of our best efforts. Infectious) arthritis is seen following the acute infectious diseases. It has much the same clinical character as rheumatism, but it does not tend to suppurate, nor is it migratory. The wrist is the most prone of any of the joints of the upper extremity to succumb to GONORRHEAL arthritis. Its well-known obstinacy and intracta- bility have made it an opprobium medicorum. Re- cently incision and irrigation of the joint have been made use of with gratifying results in this form of arthritis. Bier's passive hyperemia will do a great deal to allay the truly atrocious pains of this form of infection, and often it will go far toward effecting a cure. The brilliant results which have attended the use of antigonocoecus serum and of gonococcus vac- cines have done much to make the outlook brighter in this formerly most intractable disease. In acute rheumatism, besides the systemic mani- festations, the joints are inflamed, painful, and tender, and the articular affections tend to migrate. Rheumatic arthritis is prone to attack the larger joints. Incases of chronic rheumatism, the joints are stiff and painful but not always swollen, while on passive motion a creaking may be elicited. The muscles may become greatly wasted, and there is a tendency toward fibrous and even bony ankylosis. The treatment of the acute form is by means of alkalies and salicylates and other appropriate drugs, together with heat, pressure, and rest. In the chronic forms the best results are obtained from massage and mechano-therapy, the hot-air bath, the copious and long-continued use of akaline mineral waters, and a strict anti-rheumatic regimen. Rheumatoid arthritis, or arthritis deformans, is characterized by changes in the cartilages and syno- vial membranes with periarticular formation of new bone and great deformity. The cartilage is either thin or entirely absorbed, laying bare the bone, while at the ends of the joints osteophytes form that may cause even complete ankylosis. This is ac- companied by a thickening and contraction of the ligaments and great atrophy of the muscles. Hyper- trophy of the articular ends of the bones is common, though in some cases atrophy is observed. Neuritis is prone to occur as a complication. The treatment is by massage and hot-air baths together with forced passive motion. Both active and passive motion must be kept up long enough to remodel deformed articular ends of the bones to their normal shape by the effects of use and pressure. The stiffened joints can sometimes be advantageously broken down under a general anesthetic, but this must be promptly and vigorously followed up by long-continued active and passive motion in which the mechanotherapeutic machines of Zander are far superior to manual work. The use of thyroid extract in moderate doses is useful in some cases, as an ad- junct to other treatment, and, when possible the pa- tient should spend the winter months in a warm cli- mate. The disease has, however, a marked tend- ency to become progressive, and in severe cases but little benefit is derived from treatment of any kind. The shoulder, the elbow and the wrist occasionally show a form of arthritis, arthritis sicca vel senilis, which is much more commonly found in the hips and in the knees. This is due to atrophy of the syno- vial membrane, and shows itself practically as a defi- ciency in the lubrication of the joint. The disease is rarely extremely painful, is never entirely curable, but may be helped by treatment applicable to ar- thritis in general, with the important exception that 555 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES long-continued disuse of the joint, and above all, all fixation of the joint must be avoided as furthering the atrophy which is the essential, underlying pathological lesion. A spbain is produced when the motions of a joint are carried beyond their physiological limits, but stop short of permanent displacement of the articular ends. With this there is either a stretching or rupture of portions of the capsule or ligaments, accompanied by pain, swelling, ecchymosis, and limitation of joint motion with tenderness over the joint. Sprains are especially prone to occur at the wrist, though the elbow and shoulder are frequently affected. It is important to differentiate a wrist sprain from a Colles's fracture, and this can generally be done by determining the absence of crepitation and of an abnormal point of motion, and also by the fact that in Colles's fracture the hand is drawn toward the radial side with a more or less pronounced "silver-fork" deformity. This last condition is sometimes better appreciable to firm palpation than to the eye, espe- cially when some time has elapsed since the receipt of the injury. The use of the x-ray will, however, in most cases make the diagnosis certain. It should not be forgotten, however, that sprained wrist is a constant, and often a serious complication of Colles's fracture. The treatment of a sprain is rest, elevation of the part, and compression, with the use of cold followed later by hot applications. The use of massage from the beginning is quite successful in skilful hands, while this with passive motion is always indicated after the subsidence of acute symptoms. Ankylosis may be due to contractures of the muscles or to contractures and thickenings of the ligaments, with or without secondary growths of impeding osteophytes about the margins of the joints. The contractures which prevent the joint from moving may, in turn, be due to disturbed innerva- tion or nutrition of the muscles, or to myositis followed by degeneration of the muscle-cells proper and substitution of fibrous for muscular tissue; but the commonest cause both of muscular and of liga- mentous contracture is unabsorbed, and more or less perfectly organized, inflammatory exudate. Ankylosis of this type rarely causes complete immo- bility of the joint; it is termed "false ankylosis" in distinction from a "true ankylosis," where actual union, either fibro.us or bony, has taken place between the opposed articular surfaces. A false ankylosis is the result of an extra-articular process, while a true ankylosis is the direct outcome of an acute suppura- tive arthritis, joint tuberculosis, chronic rheumatism or rheumatoid art hritis. The treatment will depend upon the cause, and may consist of massage and forcible flexion and ex- tension of the joint. These not availing, more or less extensive tenotomy and myotomy may be practised, or the joint itself may be excised. At the elbow, where, on account of the complexity of the joint, ankylosis is particularly prone to occur, a flail joint, the result of an excision, with all its disad- vantages, gives nevertheless a much more service- able arm than can be obtained by any other form of treatment for extensive fibrous or bony ankylosis of the joint. In ankylosis due to muscular contrac- ture excision is less to be recommended. Quite a large number of cases are on record of loose bodies in the elbow-joint. Their pathological history is similar to that of loose bodies in other joints, such as the knee. The only treatment is re- moval by arthrotomy. IV. Affections of the Muscles, Tendons, and Tendon Sheaths. The Muscles. — In no part of the body are the muscles and tendons grouped in such numbers about the bones as in the forearm, and in no part of the body do the affections of these structures stand out so prominently as in the upper extremity. The commonest of all diseases of the muscles, if indeed the name of disease is applicable, is that con- dition of the muscles which results from long-con- tinued use without sufficient repose to which the name myalgia has been given. The pathological con- dition present is in the main but an accentuation of the normal condition of muscular fatigue, and is at- tended by similar symptoms, namely, tenderness on pressure, "lameness" in use, and deficient response to ordinary physiological nerve impulse (i.e. weakness in action 1 ), and, finally, involuntary and painful spasm, " twitching." These symptoms in turn are caused by too great an accumulation in the muscle of the chem- ical products of muscular activity, and this accumu- lation, again, may be the result of either or both of two factors: excessive production on the one hand, and deficient elimination on the other. As to the exact chemical bodies involved, the reader is referred to treatises on physiology; their exact nature is still a matter of dispute, but one of the best established of the waste substances is lactic acid, present in suffi- cient quantity to affect markedly the reaction of the muscle substance to delicate alkalimetric tests, and there is little doubt that this changed reaction of the muscle substance induces in its turn the precipitation of various ''leucomaines" which it is difficult for the ordinary blood current to remove promptly. So long as these decomposition products (uric acid, xanthin, hypoxanthin, acid phosphates) are not removed from the muscle the symptoms enumerated above will continue; with their disappearance the normal function of the muscle will return. The exact locality of these morbid deposits is not entirely settled, but many facts point to the probabil- ity of their being located rather in the sarcolemma and in the perimysium than in the substance of the muscle proper. The facts which would indicate this are the aggravation of the tenderness at the muscular origins and insertions, and the spread of the myalgio affection throughout the fibrous tissues beyond the points of actual muscular insertion; indeed, in no part of the body is what passes for myalgic affection, or as very closely akin to it, more obstinate and trouble- some than in the fibrous tissues just below the origin of the erector spina? muscles, over the sacrum and the sacroiliac synchondroses. It is more than probable that consecutive upon a pure myalgia may occur a rheumatic form of periostitis from extension beyond the point of bony origin or insertion of a muscle by "contiguity of tissue." This is exemplified with peculiar distinctness in cases. of myalgia affecting the muscles attached to the coracoid process of the scap- ula, where the coracoid process itself may often be found to retain for a long period a great degree of tenderness when pain may entirely have left the bodies, or the tendons of the muscles attached to it. Excessive formation of waste products comes from over-use of the involved muscle; deficient elimination may be caused by use of the muscle under unfavorable conditions, or by exposing the member to untoward conditions after its severe use, thus interfering with its prompt rehabilitation. An amount of muscle work whose catabolic products would be speedily provided for under other circumstances may induce a severe myalgia if performed when the patient was suffering from want of sleep, as many a weary obstet- rician can testify; and it is notorious that sitting in a draught after' active exercise will lead to " cold set- tling in the limbs." There is one form of this affection whose sudden and severe onset may lead to confusion in the diagnosis; this form more frequently attacks the erector spinas group of muscles, or those of the abdomen, when it is known as a "stitch in the side." This form of myalgia is probably due to a gradual accumulation of 5.J0 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arm umi Forearm, Diseases mid Injuries »>f fatigue products in the muscle, or possibly only in the fibers "f a small portion of a muscle, to the point „f irritating the affected fibers to a sudden, painful, and protracted involuntary contraction, the patient ing been unaware of the soreness of that particular muscle through the accident of not having brought those fibers into play. When once the painful traction has taken place, the irritability of the cted muscle becomes extreme and the whole muscle is brought more or less involuntarily into ited action, to "test its soreness," and a more or less persistent myalgia is found to be established until driven off by the activity of the circulation or by the exhibition of suitable remedies. Such a levelopment of a latent myalgia among the muscles of the forearm has led in one instance I have known of to an erroneous diagnosis of rupture or dislocation of a tendon. The patient was a young woman engaged in wiping dishes; of a sudden a severe -hooting through the forearm caused her to drop the dish in her hand, and certain movements of the fingers were from that time on, for many weeks after, painful and feebly executed. The diagnosis of myalgia, as it appears in the arm and forearm, is not ordinarily attended with great difficulty. The history of fatigue, or exposure, or both, will generally suggest the diagnosis, while the presence of the gouty or rheumatic diathesis, as condi- tions under which waste products are imperfectly removed from the tissues, will be allowed a certain weight in establishing the probabilities. In the upper arm the extensors (triceps) are most frequentl}' affected, in the lower arm, the flexors and extensors with about equal frequency. Occasionally the coraco- brachialis or the anconeus may be affected alone, giving rise to rather obscure pains in the shoulder and elbow respectively. Such cases are readily over- looked in a careless diagnosis. Incidentally their deep location renders treatment more difficult. The tenderness over the affected muscle, the painful and imperfect function, and the occasional fibrillary spasm are the positive factors upon which we base a diagno- sis, while the absence of fever, swelling or redness, the absence of tenderness about the joints, along the course of the nerves, or along the tendon sheaths will weigh against rheumatism, neuritis, and thecitis respectively. The absence of fibrous crepitation will also serve to aid in excluding this last affection. From painful affection of the bone or the periosteum it may be extremely difficult to differentiate a deep- seated myalgia; the absence of pain on jarring the limb, and its ready yielding, if recent, to the faradic current will serve to aid in identifying a myalgia. The prognosis is good if treatment be instituted earl}-; if treatment be too long postponed, and atrophy ensue, due partly to disuse and partly to local poison- ing of the muscular substance by the "materies peccans" of the disease, the affection may prove very obstinate and intractable, but will in almost all cases eventually yield where the persevering cooperation of the patient can be secured. It is my firm belief, however, that simple myalgia, if severe and untreated, can occasion permanent disability. The treatment of myalgia consists in efforts to throw again into solution those precipitates in the muscles whose presence impedes their function and causes the pain. This we seek to accomplish along certain rational lines, all tending to this common end. Probably the first therapeutic efforts of sufferers from myalgia were directed toward keeping the affected part warm. The rationale of this lies in inducing a dilatation of the blood-vessels, which brings a larger supply of the solvent serum into contact with the offending precipitates, thus pro- moting their solution. With the increased advent of blood follows in turn an increase of heat, which in connection with the heat added from without induces an actual rise of the temperature of the part, which i< likely to promote considerably tie- solubility of any precipitates. Recently this method of treatment has had its efficacy greatly enhanced by the devising of methods of exposing tin- affected limb to dry an- al very high temperatures. Local hot-air baths may now be procured from instrument dealers by means of which an extremity may be exposed, without damaging the skin, to dry air at a temperature of 300 to 500° E. Other ways of increasing the afflux of fresh serum to aid in the solution of precipitates are. first, Bier's passive hyperemia, by means of a constricting band- age; secondly, counterirritation, applied to the overlying skin by the use of iodine or other rube- facients, cantharidal blisters, or "firing" with the actual cautery; thirdly, moderate, active use of the muscles, when practicable without causing too much pain; every athlete is familiar with the disappearance of "muscular stiffness" (the mildest grade of this disease) under fresh exercise; fourthly, massage of the affected parts is extremely useful, particularly in the more obstinate and chronic forms of myalgia; it partly by mechanically dislodging crystals or amorphous masses of precipitated matters, forcing them into the lymphatic circulation, and partly by greatly stimulating the local circulation. Antirheumatic remedies, and the antirheumatic regime are also of use in controlling the pain of myalgia, chiefly by the solvent affect of alkalies and of the salicylates on the morbid deposits, and of these measures there is none that compares in importance with the ingestion of very large quantities of water. While massage is our best weapon against chronic forms of the malady, especially in the presence of secondary atrophy, there is no agent whatsoever that will give the immediate and lasting relief that is to be obtained from the application of the faradic current, and no more grateful patients are encountered than those who have been relieved from the misery of a myalgia by the brief application of a mild current. Within the last few years our armamentarium has been enriched with a multitude of new and efficacious means of treating this common and troublesome malady. Among these are a variety of phases of the electric current, such as the slowly interrupted gal- vanic current, the sinusoidal current, the high fre- quency alternating current and the franklinic spark, also violet light, and the many candle-power (500 or more) incandescent light. Perhaps the simplest and most commonly used of the recent methods of treatment is the application of mechanical vibration. One special point it is important to notice in the treatment of myalgia of the upper arm — namely, this, t hat the muscles which move the upper arm have their origin on the trunk; and that their function is twofold, first, that of imparting voluntary movements to the upper extremity, and secondly, that of supporting the weight of the arm. This second function is not appreciated during health, but in the presence of a severe deltoid myalgia, the six to ten pounds weight of the arm dragging upon the lame muscle is a very considerable factor in increasing the pain and a serious obstacle to recovery. In all acute myalgias, there- fore, affecting the muscles which pass from the trunk to the arm it is necessary to support the weight of the member by a firm bandage at the elbow-. The most effective device for this purpose is a Moore's dressing for fracture of the clavicle, as described under the head of fractures. Occasionally one sees cases of what are called "chronic sprains" or "strains," caused by the overuse of certain muscles, in which the pain is principally at the origin or insertion of the muscles. Tenderness and stiffness are prominent symptoms. Examples of this are seen in the so-called "base-ball pitcher's arm," "tennis elbow," etc. Such persistent over- use of a muscle may give rise to a local periostitis at one of the points of attachment of the muscle, possi- 557 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES bly resulting in necrosis, and occasionally leading to bony infiltration of the muscle, due to proliferative periostitis. In some, rather rare cases of sudden and violent contraction of the muscles, as, for instance, in throwing a stone, in swinging on the trapeze and among washerwomen in wringing clothes, actual rupture of a part, or even of all the fibers of a muscle may occur. This accident, which not infrequently befalls the plantaris longus in the leg, has been seen in the arm to affect the supinator longus (in a young woman engaged in wiping dishes), the coracobrachialis (in wringing clothes), the biceps, and occasionally the triceps. Subcutaneous muscle-rupture is more fre- quently, however, the result of direct violence exerted upon the muscle when tense than the result of pure contraction. Both the biceps and the triceps are not very infrequently injured in this way when the front or the back of the arm, respectively, is struck by a blunt object, e.g. a base-ball bat. When a consider- able muscle, like those mentioned, is thus ruptured, the picture is unmistakable provided the injury is recent. There is characteristic inability to flex the arm actively and fully with a ruptured biceps, or to extend it, with a ruptured triceps, while passive flexion and extension are unimpeded. There is furthermore evident and extensive subcutaneous hemorrhage, and, as a pathognomonic symptom, there is ordinarily readily discernible a diastasis between the two portions of the ruptured muscle, and the proximal portion of the muscle contracts to a quivering fleshy lump when spontaneous efforts are made by the patient to contract the muscle. The diastasis is frequently wide enough to permit the finger to be laid between the ruptured ends of the muscle. The I reatment is obviously by suture of the divided muscle, with the arm put up in flexion, for injury of the biceps, and in extension, for injury of the triceps. Occasionally the flexor group of the forearm, but more frequently the biceps, and rarely other individual muscles of the arm will present, either as the result of an injury with a blunt instrument or missile, or occasionally spontaneously, a rent, not of the muscle fibers, but of the overlying fascia or muscle sheath. Through such a fascial rent the muscle fibers tend to protrude, forming what is called a muscular hernia. The effect of such a herniation of the muscle sub- stance through its sheath is to weaken and impede in considerable degree the forcible contraction of the muscle, the patient complaining of insecurity and uncertainty in exercizing the limb, and occasionally of pain. Here too the treatment is incision and suture of the torn muscle sheath, after first undermining it for some distance from the margins of the rent. Acute myositis is occasionally encountered in the muscles of the arm as a result of pyogenic infection. The pyogenic type of this disease, however, is rare, and when present is but a secondary accompaniment to neighboring extensive septic processes. It may lead to necrosis of the muscles en masse, or to frac- tional sloughing, and solution of the muscle fibers in the purulent effusion. A rare form of myositis is the tuberculous, which in many respects resembles the gummatous myositis of syphilis. It bears, however, the characteristic tokens of tuberculosis, including characteristic reac- tion to tuberculin, characteristic temperature curve, etc. It appears generally in subjects presenting other and extensive tuberculous lesions. Its treat- ment, in the absence of too extensively generalized tuberculous invasion to make the operation justifia- ble, should be by partial or complete excision of the affected muscle. The most common forms of myositis are those whose origin is syphilitic, indeed it is more than probable that part of the "rheumatic" pains which precede or accompany the eruption of constitutional syphilis depend upon a light and acute irritative myositis. A commoner form of syphilitic myositis is the chronic interstitial variety depending upon a small-celled infiltration rising from the perimysium, and extending into and between the muscle bundles. These are destroyed by pressure atrophy, and become transformed into connective tissue with gradual loss of the muscle. It is a diffuse process within the muscle, and is at first generally attended with pain. Gummatous myositis may develop as a slowly growing, and perfectly painless infiltrate in the muscles. Accompanying the gummatous process there are usually found more or less extensive inflam- matory changes. More commonly, however, the growth of the gumma is more rapid, and pain, in- creased by touch and motion, is a marked symptom. The muscle in all the more rapidly growing gummata is in a state of constant contraction, the growth at first moves with the movements in the muscle. As it increases in size it becomes softer in consistency, and the muscle assumes a condition of permanent contracture. Gummatous myositis often advances beyond the muscle, and comes to involve the fascia and sub- cutaneous tissues. It becomes more prominent, softer and less movable, and finally breaks through the skin, leaving a sinuous ulcer from which necrotic masses, chiefly fascial, are extruded. After healing, which requires weeks or months, a cicatricial tissue remains which binds together the muscle, fascia, and skin (Hartley). Ischemic atrophy or Volkmann's contracture is a rather peculiar and an important condition. The following description is taken from Keen's Surgery. "The cause is interference with the circulation. Pressure on the nerves may have some influence. The circulation may be interfered with by the too tight application of splints and dressings, by the unduly prolonged use of the elastic constrictor (tourniquet), by injury to large vessels, and by exposure of the part to cold. The forearm is the region most com- monly involved, the affected muscles become densely infiltrated. Unless the cause is removed within twenty-four or forty-eight hours or earlier, the muscle fibers degenerate. The whole muscle (Fried- rich) does not become uniformly degenerated, but the portions attacked undergo contraction. "According to Dudgeon, pain is absent unless the disease is accompanied by neuritis; other authors describe pain as an early and important symptom. Within a few hours the hand becomes swollen, the phalanges flexed, and there is paralysis of the muscles. The muscles are hard, swollen and tender. If pain is absent, the seriousness of the condition is apt to be unrecognized. If splints are the exciting cause of the trouble, their pressure may occasion necrosis and ulceration of the skin, but these lesions are merely concomitants unrelated to the muscular degeneration. When recovery takes place it leaves a permanent con- tracture. When the forearm is the site of the disease, the resulting deformity is characteristic. The pha- langes are flexed on each other, but the metacarpo- phalangeal articulation remains extended. The pha- langes cannot be extended while the wrist is extended, but as soon as the wrist is flexed, the fingers can be straightened. If the muscular degeneration has been more extensive, the wrist becomes flexed as well as the fingers." Progressive muscular atrophy is a disease which manifests itself most distinctly among the muscles of the arm. It is, however, essentially a nervous disease and not a disease of the muscles; its consideration here, in connection with the muscle-, is for greater convenience only. The nerves supplying 558 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ami and Forearm, Diseases ami Injuries, of the atrophied muscles may be affected anywhere along their course, bul the principal site of the lesion is in the anterior gray columns of the spinal cord. However general the disease may subsequently heeunie.il is at first Idealized, anil t lie upper ex I remit y I hj far the must frequently involved. Affection of the right hand is said to he considerably more frequent than thai of the left, and of the muscles, either the interossei or those of the bull of the thumb first succumb. The disease, in fact, at first simulates an ulnar neuritis, but careful study will indicate the olvement of certain muscles which are supplied by er nerves. From the thenar muscles and the interossei, the disease commonly creeps up the fore- arm and thenee to the arm. or it may skill the forearm pass into the arm, although the triceps extensor muscle is usually spared. It may come to a stand- Still in either of these two places, but may involve the muscles of the shoulder, especially the deltoid. Beginning most frequently on the right side, both r extremities become involved sooner or later. In other instances in which the extremities are lived the atrophy begins in the deltoid (here again the right first). Succeeding the deltoid, the scapular and trapezius muscles may be involved in any order, while a grotesqueness of effect is often produced by reason of certain adjacent muscles retaining their natural size or even being hypertrophied. This is ticularly the case with the anterior part of the trapezius, which is almost never involved. While the shoulders remain exclusively affected, the arm and forearm may retain their usefulness and strength, I uit the power of lifting the arm from the side, and especially of raising it above the head, is lost, and if the patient wishes to lay hold of anything he must swing his arm forward with a jerk till the object is brought within reach of his fingers. The muscles of the trunk become at times involved: the pectorales, the latissimi, the serrati, and the intercostales, and even the diaphragm and the abdominal and lumbar muscles. The muscular atrophy is generally accompanied by responding wasting and retraction of the skin, so that this continues to be applied to the muscles in the usual manner. In some instances, however, this is not the case, and in these a baggy condition of the skin is added which gives its subject an appearance which has more than once rendered him valuable to the showman as the "elastic skinned man," etc. It sometimes happens, on the other hand, that the atrophy is obscured by an accumulation, between the muscles and skin, of adipose tissue, and an appearance of hypertrophy rather than of atrophy may be produced in consequence. \ second muscular symptom, more or less distinct, is fibrillar contraction. This consists in wave-like ractions running along small bundles of muscular fasciculi. These contractions occur spontaneously, or are excited by some slight stimulus, as a breath of air or a dash of water, or by tapping the patient with the fingers or passing a galvanic current through the parts, and this too in any stage of the disease, except that they do not occur in muscles wholly destroyed. Sometimes they can be felt by the patient; at other times he is wholly ignorant of them. They are not invariably present, and often they have been seen in muscle atrophy from other causes; they possess, however, a certain amount of diagnostic value, especially when spontaneous. Coincident with the wasting of muscles is their loss of function. Sensibility is in many cases unchanged, the tactile sense being as delicate as ever, and pain, except accompanying the cramps and chronic contractions of groups of affected muscles, which sometimes occur, is absent. At times, however, the atrophy is preceded by painful paroxysms, which may or may not accompany the chronic, contraction referred to. The pain is sometimes in the course of nerve trunks, hut is as often diffu e, ■■> if the muscles themselves were its seat. At other times it is variously described as a soreness, an aching or a rheumatic pain. Morbid sensations, as those of cold, numbness, and formica- tion may be experienced. Keflex excitability may be increased, while the knee jerk is said to be absent. Unusual sensitiveness to cold is sometimes noted, and SO also is the loss of muscular power under its in- llucnce, which is again restored by artificial warmth (Tyson). The lipomatosis, which has already been alluded to as affording, in some cases of muscular atrophy, somewhat the appearance of the pseudomuscular hypertrophy, may to the casual observer obscure tho diagnosis of this disease. Pseudohypertrophic par- alysis, however, almost, invariably first asserts itself in the lower extremity. Syringomyelia is another of the central nervous diseases which finds its most marked expression in the secondary changes it induces in the sensory, trophic, and motor functions of the arms. The symptoms are almost always bilateral, but a few cases have been observed in which but one side of the body was affected. The most common type is that in which the most salient features are loss of perception of pain and temperature, with retention of the tactile and muscular senses, combined with atrophy of the arms similar to that observed in progressive muscular atrophy. The atrophy usually appears in the small muscles of the hand and gradually extends upward, involving consecutively the arm, forearn, and shoul- der muscles, or it may first appear in the shoulder and upper arm and later descend to the hand. The difference depends upon whether the lower cervical gray matter is first affected with extension upward of the process, or whether the upper cervical enlarge- ment, in which are located the centers for the shoul- der muscles, is first affected. Corresponding with the atrophy there is naturally a weakness of the muscles which may go on to com- plete paralysis. Trophic disturbances are common. Changes in the joints and bones, very similar to llio-e observed in tabes, occur in about ten per cent, of the cases. The joint changes consist principally of enlargement of capsular ligaments, loosening of the joints, thickening of the capsule, changes of form in the ends of the bones, and development of bony spicule in the capsular walls. The further changes resemble those in tabetic joints. Painless fracture of the bones may occur from very slight causes, as in the case of a man who fractured the radius while kneading dough. Various atrophic changes in the skin are frequent, such as herpes, eczema, and even deep ulceration and gangrene; in rare cases amputation of the hand may be necessary; or there may be simply vasomotor changes causing lividity and coldness of the skin or the opposite, or edematous swelling of the hand. There may be sweating or dryness of the skin. The nails may be- come dry, cracked, and brittle and may drop off. An obtrusive symptom which is sometimes ob- served is the painless felon, similar to that which occurs in Morvan's disease. These felons occasion deep ulceration and necrosis of the distal phalanges of the fingers so that they may drop off. Notwith- standing this extensive ulceration the felons are painless, owing to the analgesia present (Prince). For a more accurate differential diagnosis of these different secondary muscular dystrophies, and for a more exact discussion of their pathology and treat- ment, the reader is referred to articles in this work on diseases of the nervous system. Spastic rigidity of the arms is often one of the earliest signs of chronic hydrocephalus, even before the skull begins to enlarge, and convulsions may be present from time to time. In congenital spastic rigidity, due to sclerosis or defective develop- 559 Arni and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ment of the cortex cerebri, the spastic condition is usually confined to the legs. In paramyoclonus mi'ltiplex, as the name of the disease implies, the contractions of the muscles ap- pear in paroxysms and the muscles involved are usu- ally the biceps, deltoid, and triceps in the arms, and the quadriceps femoris and calf muscles of the lower limbs. Myoclonus multiplex is a disease of adult life, and may be differentiated from chorea, which is usually seen in childhood. Sometimes the muscles in myoclonus are exceedingly irritable. Sometimes, as the result of infantile cerebral par- alysis or from reasons developing later in life, the muscles of the hand are affected by a slow, constant movement, so that the fingers assume curious con- strained and unusual postures, being moved into ex- treme or forced extension, flexion, pronation, or supination. This condition is called athetosis, and is separable from chorea in that the movements are slower, and are limited to the fingers and wrists, the arm escaping. Absolute loss of power in one hand and arm, with- out the necessary development of subsequent de- formity, results from cerebral or peripheral lesions as a rule, being rarely spinal in origin, and is called brachial monoplegia. Although the onset of a monoplegia due to cortical, subcortical, or capsular causes is sudden, the reactions of degeneration do not come on for a long period of time in such cases, be- cause the muscles in the paralyzed area are still con- nected with the trophic centers in the cord, and this affords us a valuable point in differential diagnosis. In all cases of brachial monoplegia due to peripheral lesions we find that atrophy of the muscles comes on very rapidly from cutting off of the muscles from their trophic centers in the spinal cord. The Tendons. — The want of protection of the tendons in the forearm is the reason of their frequent accidental division from incised wounds near the wrist . In the event of such division the proximal end will retract an inch or more into the tissues of the fore- arm, and naturally the function of the accompanying muscle will be totally suspended. Where several of these tendons have been divided at once, there may be considerable difficulty in identifying the corre- sponding proximal and distal ends. In any clean wound, however, union by suture should be attempted; nor would the mistaken apposition of the proximal end of one tendon to the distal end of another prove as serious a disaster as the failure to unite the severed tendon ends. In fact an intentional transplantation of the proximal end of one tendon to the distal end of another has recently been practised with brilliant success in some cases of infantile paralysis, with a view to imparting vicarious function to the paralyzed members. In uniting multiple sections of the ten- dons in transverse incised wounds of the wrist and forearm, it is important that the union should be at least between tendons traversing the same compart- ment of the annular ligament. An occasional result of a severe sprain is the dislocation of the tendons about the affected joint. The long head of the biceps is oftenest so affected, being displaced from its groove in the hu- merus. The flexor carpi ulnaris is sometimes in- jured in this way, and the tendon of the extensor com- munis digitorum, which runs to the index finger, is not infrequently torn from its bed at the back of the wrist, owing to the fact that the portion above the annular ligament stands at quite an angle to the portion be- low. Its displacement is always to the radial side. In cases of dislocation of the tendons, the muscles can still contract, but the tendon can be felt to move in its abnormal position, while the extremity suffers a partial loss of function from the mechanical dis- advantage under which the muscle works. These accidents may be treated by replacing the tendon and keeping it in position by a splint. This not availing, the tendon may be cut down upon and the torn sheath sutured or a new sheath formed by dissecting up a band of periosteum. Among the traumatic affections of the tendons we occasionally meet with instances of complete rupture. This occurs either in the course of the tendon proper, or, more frequently, at the attachment of the tendon to the bone, but rupture at the musculotendinous junc- tion is almost unknown. When the tendon is inserted into a special epiphysis, as the triceps into the olecra- non process, the biceps into the tubercle of the radius, and the supinator longus into the styloid process of the radius, so-called rupture of the corresponding tendons is usually accompanied with tearing off of the epiphysis and more or less stripping up of the adjacent periosteum, constituting what is known as a fracture "par arrachement." The tendons of the arm most frequently the subject of rupture are the long head of the biceps, and the pronator radii teres; the radial attachment of the biceps, the triceps, the deltoid, and the pectoralis major have been reported as torn from their insertions. It is not likely that rupture of a healthy tendon can occur except when the muscle is suddenly and unexpectedly exposed to severe ad- ditional strain when already in a state of contraction. The accident is generally accompanied by sudden and violent pain, by complete loss of power in the muscle, and by considerable impairment of function in the limb. The treatment will vary, according to the importance of the affected muscle and the amount of disability incurred, from simple rest, with pains to keep the limb in a position to relax to the utmost the affected muscle, to more or less elaborate operative procedures for the restoration of the continuity of the lacerated tissues by suture. It should be remembered that contractures may subsequently develop in conse- quence of muscular or tendinous ruptures. The tendons themselves are rarely the subject of disease which does not also involve their synovial sheaths as well. They may become necrotic in sup- purative processes which have invaded their sheaths, and in this case their separation will take place at the point where their intrinsic blood-vessels have bci n destroyed. The tendons are sometimes the seat of deposits of urates, and not infrequently undergo calcareous infiltration in advanced life. Ossification of their distal ends is also sometimes observed, and in some cases there is an anomalous development of sesamoid bones at the point where the tendons may form an angle in passing over bony prominences. Rheumatic deposits are sometimes found near the proximal end of the tendons. The Tendon Sheaths. — Much more common than disease of the tendons themselves is disease of the synovial membrane which surrounds them. The exact pathology of the simple irritative form of tenosynovitis is not very perfectly understood. From its etiology and course the pathological con- dition is strongly analogous to that which has been discussed under the head of myalgia, and is prob- ably due to an alteration of the synovial fluid and possibly of the endothelial cells lining the sac. It is observed to occur under conditions strictly analogous with those which induce an attack of myalgia i.e. exposure to cold and overuse of the parts. It is generally accompanied with lameness and tender: over the course of the tendon, and characteristic of the condition is the crepitation which follows contrac- tion of the muscle. Rest, heat, and counterirrita- tion are the best means for relieving the difficulty. In addition to the simple irritative form, a septic, a rheumatic, a syphilitic, and a tuberculous form of tenosynovitis are recorded. The septic form is almost invariably secondary to septic processes outside of the tendon sheaths, and in septic tenosynovitis of the forearm the locus of 560 REFERENCE HANDBOOK OF THE MEDICAL 81 II Nl ES Arm and Forearm, Diseases and Injurlrs ol primary sepsis is most frequently the hands and fingers. The disease is accompanied with a purulent effusion into the tendon sheaths, giving rise to tender oblong swellings, ill-defined on account of the dis- tention due to accompanying cellulitis, and lying iilrl with the axis of the limb. The surrounding tea are usually sufficiently involved in the pyogenic process to give rise to heat, redness, and swelling of the surface. Suppurative tenosynovitis has been known to follow gonorrheal rheumatism of the joints. The treatment of purulent thecitis consists in laying open the tendon sheaths freely, though not literally from end to end lest the tendon escape from its bed. Only in rare cases would it be justifiable to divide the annular ligament of the wrist or even to open its compartments. Great effort, however, should be made to irrigate the sac most freely with antiseptic solutions through the liberal incision above and below the bridge of tissue which it may be deemed wise to leave to serve as a bridle to hold the tendon in its bed, and particular pains should be taken to force the irrigating fluid to pass under this bridge of tissue. In dressing wounds, whether operative or otherwise, of the tendons or of the tendon sheaths, it must be borne in mind that the vascular supply of these tissues is limited and that in consequence when they have been exposed to the air it is necessary to provide carefully against their desiccation in order to avoid necrosis. In all aseptic conditions of the tendon •lis this may be accomplished by covering the exposed tissues with impervious protective strips of a-percha, rubber, or prepared mackintosh. In septic processes the use of impervious dressings is contraindicated, and provision against desiccation must be made by means of wet dressings, frequently renewed. serious and crippling a disease is purulent tenosynovitis, and so indifferent are the results obtained by ordinary surgical means, that I have deemed it not unwise to append a description of the treatment by passive hyperemia, as outlined by Bier, in his book "Hyperamie als Heilmittel." "Incipient phlegmon of the tendon sheaths. whether accompanied or not by a wound leading directly to the sheath of the tendon, we never attack by immediate operation, but, on the contrary the at tempt is made to abort the process at the outset by vigorous obstructive hyperemia (i.e. by means of a firm constricting bandage applied above the elbow). If we are not successful in this, or if there is already unmistakably present a considerable accumulation of pus, the abscess is opened, either through one large, or through multiple small incisions. We avoid very long incisions, such as extend the whole length of the ;ed tendons, because they involve the danger of having the tendon disengage itself from its sheath, allowing it to lose its proper relations with the sur- rounding soft parts, and to become desiccated and necrotic. For the same reason we abstain from the introduction of any packing or any drainage appli- ances. Indeed, a most important consideration is that gauze packing, owing to its capillarity, with- draws the nutrient fluids from contact with the tendon and thus favors its desiccation and necrosis. When, on the other hand, the wound is left to itself, the exposed tendon presently becomes covered with granulations pushing in from the sides of the sheath. Each day the accumulated pus is expressed from the 1 incisions; if necessary, the pus is flushed out with a stream of saline solution. If fresh abscess - form they are promptly incised. All operative measures are conducted under narcosis, for the sake of more thorough work. Xo splint is used. After any operation the wound is simply covered with a copious absorbent dressing, because the obstructive hyperemia generally evokes a very abundant secre- tion. The dressing must be applied very loosely, so that the limb underneath may have ample opportun- Vol. I. — 36 it v to swell under the influence of the constricting bandage, and so that the patient shall not be impeded in malting active movements of tin- fingers. From the very first day, tin- surgeon executes daily pa movements of the fingers in which every joint of each finger is both Hexed and extended. Only in this way is it possible to obtain full restoration of function. Occasionally, even in twenty-four hours, the tendons will have contracted adhesions with die surrounding parts, and under the passive flexion and extension, the tearing loose of these adventit i<>us attachments is accomplished only with a very perceptible cracking. These maneuvers, which under other conditions would be cruelly painful, are relatively easily borne owing to the conspicuous analgesic effect of the obstructive hyperemia. A further extension of the suppuration, v. Inch one would perhaps not unnaturally dread, we have not encountered as the result of such passive movements. The constricting bandage is removed from above the elbow a certain length of time before beginning the passive movements, to avoid bleeding of the granulations. The best time to undertake the passive movements is in the pause between two periods of hyperemization. (The general recom- mendation in the treatment of acute septic processes is to leave the constricting bandage in place, above the elbow, for from twenty to twenty-two hours a day.) The patient, furthermore, is urged to perform active movements of the fingers at frequent intervals." The results which Bier has attained under this method of treatment are most satisfactory, and are far in advance of any attained before his method of passive hyperemia was introduced. It is likely that still better results can be obtained by combining with the treatment by passive hyper- emia, the use of bacterial vaccines. This would necessitate a careful determination of the nature of the infecting germ, and the application of a corre- sponding vaccine. If the streptococcus were found to be the cause of the septic process, such a vaccine would probably- prove more efficacious if grown from autogenous cultures. Like all diseases of the fibrous system, tenosynovitis is very prone to occur in arthritic subjects, and the rheumatic form of texosyxovitis has a very disagreeable tendency to become chronic. In the acute stages alkalies and the salicylates will afford relief to the patient. In the later stages lithia and the iodide of potassium are the most servicable drugs available; while the exposure of the limb to high temperatures in the hot-air bath, together with massage, and active and passive motion carried on in spite of the soreness, will do much to restore the supple action of the arm. The tuberculous form of tenosynovitis begins in a very insidious fashion. It may be primary in the tendon sheath, but is frequently secondary to a tuberculous process in the adjacent joints. It is, like most tuberculous processes, of very slow growth, covering a period sometimes of years, with times of improvement under rest, but with great proneness to recur as soon as the limb is again put to its customary use. It develops frequently after some traumatism such as a sprain or a contusion, and the differentiation from the simple irritative or from the rheumatic form is not at first easy. After a while there will almost always be developed along the course of the tendon the characteristic flat or oval swelling, caused by eTusion into the sheath and thickening of the walls of the sheath itself. This swelling may take on more or less of an hour-glass shape from confinement of the tendon beneath the annular ligament. The disease may remain confined to one portion of a single tendon -heath, but tends to extend both upward and downward; also to attack neighboring tendons and even to invade underlying joints. According to Park, there are two pathological forms 561 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of the disease: one is a fungous form distinguishable by the growth of exuberant granulation tissue of a gelatinous appearance surrounding the tendon on the inner side of' its sheath. In the other form, known as hygroma, the inner surface of the tendon sheath is covered with small growths, which become detached, forming small, hard kernels known as rice bodies. These rice bodies are the result of fibrinoid degenera- tion, i.e. the degenerated villous growths which are fibrinous in character become loosened, forming free kernels. Until recently, this form of disease was supposed to have no connection with tuberculosis. It is now distinctly established that these bodies con- tain tubercle bacilli. The same condition may be found in tuberculous joint disease where they develop from a fibrinoid degeneration of tuberculous granula- tions on the synovial fringes. If the disease is allowed to run its course, suppuration ensues, forming sinuses involving the skin which eventually breaks down. These with the resulting cicatrices greatly impair the use of the hand. The treatment of tuberculous tenosynovitis is essentially the same as that of tuberculous joint trouble, and consists at first in the immobilization of the arm by suitable splints, with moderate pressure, together with the administration of appropriate tonics and careful attention to hygiene. It is essential to differentiate positively the tuberculous form of the disease from the simple irritative and the rheumatic form. Massage so preeminently useful in the treat- ment of the two latter forms, is absolutely and positively contraindicated in tuberculous synovitis. The possible usefulness of dry heat, by means of the hot-air bath (active hyperemia), is not altogether settled, though it would seem to be a rational thera- peutic measure. Less doubtful is the beneficial effect of "obstructive" or "passive" hyperemia by means of a constricting bandage above the elbow. The application of this method of treatment to tuberculous lesions demands, however, considerably more care, judgment, and circumspection than its application to ordinary septic processes. Three points are insisted on by the advocates of passive hyperemia in applying it to all tuberculous lesions: first, the bandage must be very lightly applied, so as to induce but a mild degree of venous obstruction, as opposed to the much firmer application of the bandage in ordinary forms of sepsis; secondly, the bandage should remain in place a much shorter time, from one to two hours a day, instead of twenty to twenty-two hours; and, thirdly, the treatment must be patiently continued for a long period, several weeks or months. Where this method of treatment is applicable, it has the further great advantage that, at least during the time that the constricting bandage is in place, both active and passive movements of the fingers can safely and advantageously be carried out with comparatively little pain. Such active and passive exercise of the fingers naturally very greatly favors complete restoration of function after eventual recovery from the tuberculous process in the tendon sheaths. Without the use of passive hyperemia, such movements of the fingers are counterindicated in tuberculous tenosynovitis, until after complete subsidence of the infectious process, and their use at so late a date can, in the nature of the case, yield only indifferent results. Failure to secure improvement by the above means would justify us, as in cases of joint tuberculosis, in proceeding to operative meas- ures. The simplest of these consists in aspirating the fluid contents of the tendon sheaths and in injecting into them a tcn-per-cent. emulsion of iodoform. Should this fail to control the process, the tuberculous area should be cut down upon, the blood-supply to i lie .inn being first cut off with an Esmarch bandage, and any suspicious granulation tissue scraped away with a small curette. At any point where the tendon itself seems hopelessly affected, it should be freely resected and an effort shoiuji be made by splitting and grafting the tendon to compensate for the defect. Even should this be impossible, the function of the tendon may better be sacrificed than to expose the patient to danger of loss of the limb or even of life. Syphilitic tenosynovitis may exhibit itself in an acute and chronic form, not easy to differentiate by symptoms alone from simple and rheumatic inflamma- tion of the tendon sheaths. Both of these forms of syphilitic thecitis are seen in early syphilis, and I have myself observed one marked case ending in resolution after some months of treatment, in a case of hereditary syphilis accompanied with syphilitic pachymeningitis. The gummatous form is almost invariably very late in development, occurring often fifteen or twenty years after infection. It is recognized as a round or spindle-shaped swelling involving the tendons. It grows slowly and painlessly, remaining as a gumma- tous swelling becoming calcareous, or extending to the surrounding tissues, the fascia and the skin. Synovial cysts of the tendon sheaths, other- wise known as weeping sinews or ganglions, occur with greatest frequency about the wrist, whether just above or just below the annular ligament. There are cases met with, however, in the lower part of the forearm, both on the flexor and on the extensor tendons. Their exact pathology is a matter of dispute, but it is fairly well established that they rarely communicate with the synovial sac proper. They not infrequently contain rice bodies such as are found in the synovial sac in cases of tuberculous disease, but their almost invariably benign course would make it seem improbable that their origin should be tuberculous. These little cysts frequently disappear spontaneously, and often their disappear- ance can be hastened by moderate pressure long continued. More obstinate cases can be dealt with by free subcutaneous puncture with a sharp bistoury or tenotome and the expression of their contents by digital pressure into the surrounding cellular tissues. Some cases may demand free incision and extirpation of the cyst walls, an operation which must be con- ducted with careful antiseptic precautions, on account of the close association and occasional continuity of the cyst with the tendon sheath proper. V. Affections of the Blood-vessels. The Arteries. — The blood-vessels of the arm are subject to the same diseases as the blood-vessels elsewhere in the body. The anatomical position of the radial artery is important from its frequent use for taking the pulse, and it should be remembered that it may be absent in rare instances; or it may be much smaller than normal, terminating in muscular branches above the wrist; or it may lie upon the deep fascia instead of beneath it; or it may be covered by fascia so thick and hard that the pulsation cannot readily be transmitted to the finger tips; finally, it may turn backward beneath the extensor muscles of the thumb. When in its normal position it is easily felt, pulsating almost subcutaneously over the bones of the wrist. Atheroma of the arteries manifests itself through thickening of the vessel wall, either localized or diffuse, and often accompanied by the deposit of calcareous salts until a condition of the vessel is produced well expressed by the term "pipe-stem artery." It is most readily appreciable in the radial artery near the wrist. Its chief importance in this connection is not with regard to the function of the vessels of the arm, but as an indication of the condi- tion of the vascular system throughout the body. The vascular sclerosis will often be found more marked in the right arm than in the left, in individuals 562 RKl-'KKKXCK HANDBOOK OF THE MEDICAL SCIENCES Ami and Forearm, Diseases and Injuries of such as stone cutters and blacksmiths who habitually perform much heavier labor with that arm than with the left. When this condition of arteriosclerosis is found to be present, it is an important guide to the surgeon in leading him to make a guarded prognosis aa to the result of severe operation anywhere in the body. Aneurysms occur in the vessels of the arm as They may be present at any age; indeed Schmidt reports' an aneurysm of the radial artery in an Infant of eight weeks. The traumatic forms affecting the arm are chiefly ■ springing from the axillary artery and showing in the arm pit. The arteriovenous form of an- eurysm was formerly quite a common occurrence v. lien venesection was more generally practised. The adjacent artery being wounded by the incision ,-ii opened the vein, adlie-ions form Viet ween the two vessels and part of the arterial blood is thrown into the vein at each pulsation, the vein greatly dilat- ing under the strain. iiD aneurysms are occasionally met with on t he forearm. They are formed of dilated and tortuous arteries. In a ease that came under my observation, tumor extended from a little below the elbow almost to the wrist, and was about three inches wide. On operation a mass of dilated arteries was found lying in the superficial fascia, fed by numerous branches "rating the deep fascia from below. The treat- ment of this form of aneurysm, which stands on the der line between tumors and malformations, con- in thorough extirpation, approaching the mass of pulsating vessels from the periphery and tying all the feeder- at their point of emergence from the deep ia. With careful dissection, working from the - toward the center of the tumor, dangerous hemorrhage can usually be avoided. The diagnosis of aneurysm can usually be made by observing that the tumor has an expansile pulsation which ceases on application of firm pressure on its proximal side. In the case of cirsoid aneurysm in which the feeders are numerous and come from the parts directly under- neath the tumor, pressure on the proximal side will not suffice to interrupt the pulsation of the mass. A characteristic bruit, can in most cases be heard over the tumor. The treatment of aneurysm of the upper extremity does not differ from the treatment of the condition elsewhere. The Veins. — The veins of the upper extremity are subject to the same affections as those elsewhere in the body; such as 'wounds, phlebitis, thrombosis, and varices. The condition of the veins of the hand and fore- arm is a valuable index of the condition of the general circulation as regards aeration of the blood and pos- olistruction to the venous circulation. These veins dilate when the heart is weak, or when there is any impediment to the return circulation in the do- main of the vena cava superior. Phlebitis may be caused by inflammation near the vessel, by thrombus formation, by traumatism, or by direct infection. It gives rise to pain and tender- ness in the course of the vessel, to edema and discolo- ration of the skin, and if at all extensive, systemic symptoms occur which are those of mild or severe sepsis. The treatment of simple phlebitis consists first of all in rest, which should be insisted on as most im- portant to prevent the detachment of emboli. Next it is necessary to secure as near an approximation to asepsis of the intestinal tract as may be practicable, and finally some benefit may be expected from the use of antiseptic and stimulating substances applied along the course of the affected vein, such as a fifty- per cent, ointment of ichthyol or Crede's silver oint- ment; the object of the treatment being to maintain the intergrity of the thrombus within the inflan el until such time as .shrinking of the coagulated fibrin may allow a partial restoration of the vascular ■ ■anal, and to stimulate the absorptive function of the perivascular lymph channels. Upon the first in- dication of septic infecti f the thrombus, as denced by chills and septic fever, or by local abscess formation, it is proper and necessary to incise the tissue- freely over the affected vessel, to clean out the septic clot, and establish free drainage. During such an operation it may be possible to restore the patulousness of many adjacent veins which may have become thrombotic, by extracting from their lumen long, more or less linn clots oil coagulated blood and fibrin. Great care, however, must Be used in manipulation of the affected limb to avoid break- ing loose portions of the blood clot within the vi which might be carried as emboli to the lungs or to the brain, and give rise to dangerous or even fatal in- farctions. Thrombosis is due to conditions that slow the blood stream associated with abnormal condition- of the endothelial coat. It gives rise to sudden and severe pain and to edema on the distal -ide of the coagulum. The treatment is essentially that of the phlebitis, which is an almost invariable attendant. Varices are rare in the upper extremity, owing to the less unfavorable action of gravity as compared with the lower extremity, but they may occasionally be found. VI. Affections of the Lymphatic Vessels, Glands, and Burs^e. The Lymph Vessels and Lymph Glands. — In con- sidering the affections of the lymphatic system of the arm, one anatomical peculiarity should be borne in mind — namely, that the greater part of the lym- phatic current from the hand and forearm passes directly to the axillary and subscapular nodes with- out traversing the epitrochlear gland and the other lymphatic nodes at the bend of the elbow. The importance of this course of the lymphatic canals is indicated in cases of septic and malignant disease of the hand, as some cases on record tend to prove that the lymphatic vessels, as compared with the lymphatic nodes, may with considerable impunity serve in the transmission of both septic and malignant particles. Thus in cancer of the hand, with more or less extensive involvement of the axillary nodes, it has been recorded in some cases that amputation of the hand and radical extirpation of the axillary lymphatics has succeeded in leaving the patient free from recurrence of the disease, and in a similar manner we frequently find the axillary glands fatally compromised and breaking down into abscesses with the lymphatic vessels, by which infection from the hand must have travelled, remaining to all appearances intact. It behooves the surgeon in all cases of disease of the distal part of the upper extremity to examine with care the condition of the cubital and axillary glands and to palpate also the course of the deeper lymphatic vessels, which is to all intents and purposes that of the main arteries. The epitrochlear node is situated in the bicipital sulcus just in front, of the inner epicondyle of the humerus. It is one of the first glands to become en- larged and indurated in the general adenitis of syphilis. Elephantiasis appears occasionally in the arms, but more rarely than in the lower extremities. Lymphangioma is also rarely met with, but may occur, particularly along the course of the deep lymphatics. Lymphadenitis may of course affect the nodes of the arm as those elsewhere, and is due either to infection in the acute form from some focus of sepsis on the line of drainage, or, in the chronic 563 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES form, is usually due to tuberculous or syphilitic dis- ease. As in all cases of adenitis, it is important to study the anatomical distribution of the lymphatic vessels which center in the affected node with a view to determine the portal of infection. The axillary glands may be involved as a result of disease of the upper extremity, but more frequently as a result of disease of the thorax and of the neck. The Bursa-. — of the bursa? of the arm that most frequently diseased is the one over the tip of the olecranon process. This bursa when inflamed and distended gives a characteristic alteration of the contour of the arm. It is sometimes present as an occupation lesion, and is known as "miner's elbow." The type of inflammation present may be either a simple traumatic bursitis, a septic bursitis, or in some cases a gummatous bursitis. In addition to these are the various forms of secondary bursitis due to extension of disease of the bone or of the joint. The only ease in which the diagnosis of bursitis is likely to offer any difficulty is in its earlier stages before effusion in the bursal sac has taken place. In this case it may be difficult to differentiate it from perios- titis and perhaps from rheumatism. The treatment of simple bursitis should be direct- ed either toward causing absorption of effused fluid, or in default of this, toward the obliteration of the sac. To this end it is wise in the acute form of the disease to try the effect of heat, compression, and the use of various agents such as iodine and ichthyol, whose function it is to stimulate lymphatic absorption. Later in the disease a different form of therapeutic effort will be more likely to be successful, ranging from tapping alone, to tapping followed by the injection of irritating fluids, if necessary to incision and packing, or even total excision of the walls of the bursa. In the septic form of the disease the contents of the bursa will probably be purulent and the surround- ing tissues will be angry and inflamed, and what was in the simple form of the disease a painless fluctuating tumor may take on all the characteristics of an acute abscess. In this case no treatment is of avail which does not involve prompt and free incision and the evacuation of the pus. It is particularly in septic cases that the danger of joint involvement by con- tiguity of tissue must be considered. In the other forms of disease of this bursa, the liability to second- ary joint involvement is slight. As already stated, the bursa frequently becomes sympathetically involved in any of the diseased processes of the joint (rheumatism, tuberculosis, syphilis, etc.) ; and in view of this we are not surprised to find occasionally an acute syphilitic bursitis over the olecranon appearing at the time of the severe joint pains which characterize the earlier stages_ of secondary syphilitic invasion. This type of bursitis tends to spontaneous amelioration and subsides pari passu with the joint affection. A more characteristic form of syphilitic bursitis occurs in this region as a late secondary lesion (second or third year). This difficulty is independent of the joint itself and consists in the development of gum- matous nodules in the wall of the bursa, presently enlarging and becoming confluent until the whole bursa represents one large gummatous mass. The process soon extends beyond the walls of the bursa and involves the skin in gummatous infiltration. When the skin has become involved, this vulnerable mass is very prone to pyogenic infection and second- ary ulceration of an obstinate and destructive character. Like syphilitic affections elsewhere, in the absence of special constitutional depression the m will yield readily to the combined use of anti- syphilitic ami antiseptic measures, neither of which may suffice for a cure. There are two other bursa? connected with the upper extremity whose surgical importance was not 564 fully appreciated until recently emphasized by the work of Goldthwait, of Boston, from whose work on "Diseases of the Bones and Joints" the following paragraphs are largely taken. These two bursas, the subacromial" or "subdeltoid" bursa and the "subcoracoid" or "coracobrachialis" bursa, are both functionally connected with the shoulder joint. The subacromial bursa is situated under the acromial proo cess, outside of the capsule of the shoulder joint, and extends over the greater tuberosity of the humerus and out under the upper part of the deltoid muscle. In raising the arm from the body at the side (abduc- tion), the surfaces of this bursa glide over each other, and if for any reason the bursa becomes inflamed, this motion will be attended with pain, and if such inflammation exist or adhesions have formed, motion will be limited, and the extent of the limitation will depend upon the. extent of adhesion formation. If the cavity of the bursa is wholly obliterated, all rota- tion and nearly all abduction at the shoulder joint will he impossible. Pain is usually referred directly to the location of the bursa or over the situation of the deltoid muscle, frequently, likewise, to the attachment of this muscle to the humerus. The subcoracoid bursa is situated betweed the tip of the coracoid process and the outer surface of the shoulder joint as it extends to and over the lesser tuberosity of the humerus. As the result of a posture such as occurs when the shoulder is habitually carried forward (the round-shouldered or stoop-shouldered attitude), the lesser tuberosity of the humerus rests against the tip of the coracoid process, and so too in many occupations the arm is used so that these two bones are in contact more constantly, or with more force than is normal, under which circumstances the subcoracoid bursa becomes inflamed. If such an inflammation occurs, there will be pain and sensitive- ness with limitation of motion. This limitation of motion at the shoulder joint, when caused by adhe- sions between the two layers of the subcoracoid bursa, is such as one would expect if the anterior part of the capsule of the joint were attached to the coracoid process. Such an adherence of these structures would not materially interfere with flexion or exten- sion of the arm, as long as motion was made in the anteroposterior plane, or with raising the arm from the side, provided the motion was made in a purely lateral plane, because in all these motions the sub- coracoid bursa is comparatively little used. If, however, rotation is attempted, either with the arm at the side or when the arm is raised, limitation is at once apparent, because in rotation the lesser tuber- osity of the humerus must either glide over (in inward ' rotation) or move away from (in outward rotation", the coracoid process. It is this limitation that makes difficult the putting on of a coat or similar garments, the dressing of the hair, the fastening of the bands of shirts, etc., all of which involve movement of these bones in rotation one upon the other. If the sub- coracoid bursa is inflamed, pain is usually located just outside the tip of the coracoid process. At times pain is referred to the deltoid region or down the arm, t lie region of the attachment of the deltoid to the humerus being a common place, or along the course of the ulnar nerve. Occasionally the whole arm and hand are painful, and associated with this there may be disturbances of circulation, the whole condi- tion appearing like a true neuritis. The treatment of subacromial bursitis is practically that outlined above for bursitis of the elbow, with this addition that the weight of the arm must be supported by a sling, either a "mitella" or the more satisfactory Moore's dressing for fracture of the clavicle. The special treatment of subcoraci bursitis should be based on the etiology of the condi- tion, as explained above, and should include proper means, either by gymnastics or by shoulder-brai to do away with the causative round-shoulders. Its REFERENCE BANDBOOK OF THE MF.DICAI. SCIENCES Arm and Foreamii Diseases and in j uries ol general treatment is by heat, rest, counterirritation, etc. When extensive and firm adhesions have formed, these can sometimes be broken up by forced manipu- lation under an anesthetic. In sonic cases it \\ill be fouml that the cavity of the bursa; lias become so completely obliterated that in spite of all manipula- tions the adhesions re-form, and improvement is impossible from such methods. Under such circum- uces an operation should be performed and the bursa' removed. Both of these bursa? are easily hed, and following the complete removal of the bursal tissue, normal function is often obtained, the nee of the bursa; seemingly being of little im- portance. VII. Affections of the Nerves. The nerves of the arm and forearm are liable to the usual forms of disease of these tissues elsewhere (neuralgia, neuritis, etc.), with similar symptoms and demanding similar treatment. The main interest hing to disease of the nerves of the arm is due anatomical distribution, giving motor and iiv disturbances in certain well-defined regions. The three- chief types of such lesions are exhibited ectively in interference with the function of the ulnar, of the median, and of the musculospiral nerve. In ulnar paralysis, the muscles affected are the ulnar half of the deep flexor of the fingers (perforatus), the ulnar flexor of the wrist, the hypothenar muscles, the two external lumbrical muscles, all of the interos- adductor pollicis, and the inner head of the Bexor pollicis brevis. The position assumed by the hand, due to the unopposed action of the antagonist muscles, is characteristic. The hand becomes more -- law-shaped and the condition is known as ■'main en griffe. This typical position is assumed by the hand only when the paralysis has lasted some time (three or four weeks or longer). The wrist is slightly bent backward and to the radial side of the irm by the unopposed action of the extensors and flexors of the radial side of the wrist and of the extensor carpi ulnaris. It is the defect of the interossei which gives, however, the most marked and characteristic deformity of ulnar paralysis. The fingers cannot be Hexed at the first phalanges nor extended at the md and third, and in consequence of this, through the continued action of the extensor communis digi- torum, the first phalanges are markedly over-extend- ■ wing to the w-ant of opposition from the lumbri- cales and interossei, while the continued action of the flexor sublimis and the unparalyzed portion of the flexor profundus digitorum bring the second and third phalanges into extreme flexion. The loss of ation in ulnar paralysis varies considerably: in some eases the sensation is lost in the little finger and the ulnar portion of the ring finger, also throughout the ulnar portion of the palm and the dorsum of the hand. In other cases there is but little attendant anesthesia. The second marked picture of nerve lesion in the forearm is found in paralysis of the median nerve. Destructive injury to this nerve above its muscular branches causes paralysis of the flexors of the fingers excepting the ulnar half of the flexor profundus, and Of the other muscles to which the median is distrib- uted: to wit. the pronators, the flexor carpi radialis, the two outer lumbricales, and all the muscles of the ball of the thumb, except the abductor pollicis and the inner head of the flexor pollicis brevis. The flexion of the wrist and of the hand, and the pronation of the forearm are very greatly impeded but not altogether abolished by the loss of function in these muscles. The flexor carpi ulnaris is still in action and ■ pronation is possible thourgh the weight of the hand when the supinators are relaxed. The extension and abduction of the thumb are characteristic, and the thumb cannot be made to touch the tips of the fingers. Flexion of the two distal phalanges is no longer possible, though thi Si I phalanges are flexed by the interossei. The loss of sensation i- again variable; the most characteristic distribution ol thesia being the thumb, index and middle' fingers, and the radial side ol the ling finger with the radial side of the pal f t he hand. 'I a< ton of t he dorsum of the hand is not greatly affected. Again, a characteristic appearance of the hand and forearm is produced, with great atrophy of the forearm on the radial side and in front . I he wrist is inclined ti ulnar side, and the thumb, whose flexor and adductor muscles are wasted, is usually rotated outward so that its palmar surface is on a plane with that of the wrist and t he fingers, as in api The third characteristic picture of injury to nerves of the arm is thai afforded by paralysis op hi musculospiral nerve. In paralysis of the musculospiral nerve loss of power occurs in all the extensors of the forearm and of the wrist and in the supinators, with the occasional exception of the supi- nator longus. The wrist drops and the finger flexed at their distal joints. Sot xtension of the fin- however, can be obtained through the action of the interossei and lumbricales. The typical distribu- tion of the anesthesia after actual division of the nerve above its cutaneous branches is along the outer part of the arm from the insertion of the deltoid to the lower third of the forearm, and there is more or less affection of the sensation of the dorsum of the hand, though in many cases there is little or no involve- ment of sensation. The ulnar nerve is more exposed to injury than any other nerve in the body. In the wrist, at the elbow, and in the upper arm the nerve is liable to division from incised wounds, to pressure or contusion, or to involvement in fractures of the bone. Some- times an apparently spontaneous ulnar neuritis is observed in persons otherwise in good health. One peculiar accident is liable to affect the ulnar nerve as it passes behind the inner condyle of the humerus, namely, dislocation from its bed. This accident is accompanied with more or less neuralgic pain referred to the region of distribution of its cuta- neous branches, and with more or less involvement of the functions of the muscles to which it is distrib- uted. The pain as well as the motor symptoms will be most marked when the arm is flexed. In short there is excited in the nerve at this point a localized neuritis. The accident, which is rare, may occur spontaneously during violent use of the arm, as in ball-playing and gymnastic exercise, or as the result of a contusion. Pain, numbness, and tingling along the ulnar side of the forearm and of the hand will indicate the moment of its occur- rence and a cord can be felt running along the inner side of the epicondyle which reveals itself as the dis- located nerve through the aggravation of all these symptoms when pressed upon by the examining fin- ger. To avoid extension of the neuritis and all the undesirable sequela; of nerve degeneration, it is im- portant that the nerve should be returned to its bed and securely fastened there. For this purpose a free incision should be made over the course of the dis- located nerve and a firm flap of connective tissue should be dissected up from the inner side of the condyle and turned outward over the nerve so as to bind it in its proper bed. The edge of this flap of connective tissue should be sutured to the capsular ligament of the elbow joint or to the periosteum of the humerus. It is wiser not to allow the needle to pass through the nerve sheath for fear of exciting neuralgic pains. The arm should be put up and fixed in ex- tension and this position maintained until the parts shall have firmly united. If the symptoms of neu- ritis in the mean time have disappeared, the limb should be treated with massage, faradization, coun- terirritation, active and passive motion, etc. 565 Arm and Forearm, Diseases and Injuries of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The median- nerve is often injured, most fre- quently in incised wounds of the wrist. In the fore- arm it suffers in case of fracture of the ulnar and radius, and just above the elbow its course to the bicipital groove exposes it to injury. The nerve per- forates the pronator radii teres, and it is possible for it to be injured in forcible contraction of this muscle without direct external violence. The muscclospiral nerve is generally the sufferer in crutch paralysis from pressure in the axilla. Its close connection with the humerus leads to its fre- quent injury in case of fracture and to its frequent involvement in the callus or between the fragments. The most frequent cause of the paralysis is, however, damage to the nerve during sleep, the patient lying upon a hard bed with his arm under him. This is seen particularly in drunkards. In many cases this injury of the musculospiral nerve is due not so much to' pressure as to stretching of the plexus by prolonged extension of the arm above the head. It is important for the surgeon to bear this in mind, as it is the fre- quent cause of arm paralysis after anesthesia. The prognosis in paralysis of this description is almost invariably good; the most potent therapeutic agent being faradization of the affected muscles. Progressive muscular atrophy and syringomyelia, together with the other spastic and paretic affections of the arm, though more properly due to nerve influ- ences than to actual affections of the muscle, have nevertheless, for the sake of convenience, been treated above under the head of affections of the muscles. VIII. Hysterical Lesions. The elbow is a favorite seat for hysterical lesions, and the arm as a whole is frequently declared by the patient to be powerless, or may be held by perverted volition in some constrained attitude which may be the more natural one of extension, or of partial flexion, or again some strange or bizarre position from which the patient declares herself unable to move it. The differentiation of hysterical from organic disease of the arm may be extremely difficult. Hysterical affections simulate especially disease of the joints. The differential diagnosis has been formulated by Dercum as follows: Hysterical disease of the joints is not associated with deformity and shortening of bone, nor with the formation of pus, nor with the local rigidity, nor with the septic tem- perature that is seen in tuberculous diseases. The stiffness is caused by contracture of the_ muscles, which is usually much more extensive than in organic disease, and the pain is usually more diffuse and more spontaneous. There are, moreover, characteristic mental and physical stigmata present. The hyster- ical patient dreads to move or assist in the examina- tion of the limb, and obviously dwells upon each symptom, while she is very apt to have segmental anesthesia in the affected limb or even hemianesthesia of the body. A very significant symptom is paralysis of the limb, which is never present in tuberculous joint disease. Finally, under full etherization the hysterical joint is found to be freely movable in all directions. It must not be forgotten, however, that hysterical symptoms may be added to those of genuine organic disease of the joint. Hysterica] paralysis may be caused by emotion, such as fright, anger, chagrin, or disappointed love. It may vary in degree from slight loss of power to total palsy. The deep reflexes of the affected side are usually increased and the skin reflexes abolished. The tendency to contracture is often marked: some ca es, however, present a flaccid type. In mild cases the nutrition of the limb is not affected, but in severe ca es of long duration slight but distinct loss of volume may !"■ noted. True atrophy with reaction of degeneration is practically unknown, and when present must throw a doubt over the exactness of the diagnosis. Hysterical paralysis is often accom- panied also with anesthesia or hyperesthesia. The anesthesia is likely to be sharply defined and limited to the paralyzed "part. The boundary of the anes- thetic area will be at right angles to the long diameter of the limb. The paralyzed part may become edematous and blue or mottled. The hyperesthesia accompanying hysterical paralysis is usually hyper- algesia. This hyperalgesia may be attended with contracture. The painful cramp-like state of the muscles causes the patient to cry out and to shed tears. Hysterical paralysis is not as a rule confined to the distribution of particular nerve trunks; in other words, it is central, not peripheral. Contracture is very likely to coexist with paralysis in hysteria, still this is not a constant rule. Neither is the reverse true: that a contracted limb or muscle is always paralyzed. Hysterical contracture is most obstinate and resisting, being very difficult to overcome even with great force. Moreover, the antagonistic muscles are involved; in other words, the limb is drawn into a vise-like immobility. The contracture is sometimes so persistent that it does not relax even in sleep. It does relax, however, under ether or chloroform. The duration of hysterical paralysis may be greatly prolonged. Some cases recover promptly, but others persist so long and simulate so closely the effects of organic disease that even the most careful observer may come to distrust the exactness of his diagnosis. The termination of hysterical paralysis is sometimes sudden, following some shock or strong mental or moral impression. Sometimes, however, recovery is gradual under well-directed treatment. IX. Tumors. Of the tumors affecting the arm and forearm none is peculiar to this locality. Keloids following si of any sort are found here as elsewhere, as are tin other forms of neoplasm which may develop from the skin or its appendages. Fibromata may occur on the arm in the form of painful subcutaneous nodules over the course of the superficial nerves. Lipomata are found with considerable frequency upon the upper extremities. They are most commonly of the cutaneous variety, and are found chiefly upon the posterior side of the arm and upon the ulnar side of the forearm, frequently also upon the shoulders and over the scapula. They have also been found burrowing beneath the muscles of the forearm. Sarcoma sometimes occurs here as a primary growth, usually in the callus of a fracture or as a tumor of the bone. Secondary metastatic sarcomata may of course be deposited from the blood-vessels in the arm as elsewhere. In this case they are generally seen as subcutaneous sarcomatous nodules. Carcinoma very rarely occurs excepting as a secondary growth from epithelioma of the hand. Epithelioma of the hand in turn develops with com- parative frequency in old age from purely benign \\ which are so frequently encountered upon the fingers, and a case has recently come under observation in which a verrucose condition existed symmetrically on the extensor aspect of each elbow, suggesting the possibility of a primary carcinoma in this region with a pathological history similar to that of epithe- lioma of the hand. Leonard W. Bacon. Army Medical Department.— The Medical Depart- ment of the U. S. Army received the organizal ion « Inch it has at the present time (1912) by the Act of April 23, 190S, by which it was largely increased and greatlj improved in status and efficiency, ruder the Army Regulations "The Medical Department is charged with the duty of investigating the sanitary condition 566 REFERENCE HAND ROOK OF THE MEDICAL SCIENCES Army Medical Department of tlic Army and making recommendations in refer- ence thereto, of ad\ ising with reference to I he location ,,i permanent camps and posts, the adoption of s . tenia of water supply and purification, and the ,li |„,sal of wastes, with the duty of caring for the sick and wounded, making physical examinations of officers and enlisted men, the management and con- trol of military hospitals, the recruitment, instruction, and control of the Hospital Corps and of the Nurse I lorps, and furnishing all medical and hospital supplies except for public animals." The organization of the Medical Department is as follows: ill I he Surgeon-General, who is chief of the Department; the Medical Corps; The Medical Reserve Corps; The Dental Corps; The Army Nurse Corps; The Hospital Corps; 7) The clerical force and other civilians employed from time to time under the authority of the annual appropriation acts. To these might be added the civilian physicians employed under contract, once a large and important class who supplemented the commissioned medical ris and made good the deficiency of numbers of the latter in time of military exigency. Since the lion of the Medical Reserve Corps, however, it is as commissioned officers of this corps that civil physicians are called into the Army when their services are needed in time of war or other necessity only a few contract surgeons are now employed for duty of a special character or at special localities h as arsenals and remount depots. The status, duties, and responsibilities of these several classes will be stated in order. (1) The surgeon-general has the rank, pay, and .inres of a brigadier general and is the Chief of Medical Department. As the head of a bureau of the War Department he is charged with the supervision of the expenditure of the Medical Depart- ment appropriations and is the adviser of the Secre- tary of War and the Chief of Staff upon matters ins; to the health, sanitation, and physical fitness of the Anny. and the administration of the medical service in all its branches. He exercises military control over the general hospitals, medical supply lots, hospital ships and trains, but not over the medical personnel and medical units which are under command of officers of the line of any grade, ept in so far as relates to duties, reports, and supplies of a purely professional nature. The Surgeon-General is not only the ranking officer of the Medical Corps and Chief of the Medical Depart- ment, but is also at the head of the Surgeon-General's office, a bureau of the War Department, which latter is one of the great executive departments through which the government is administered. The War artment is not a part of the Army, although the ruing power for it, and containg many army officers among its higher personnel, and in the same way the Surgeon-General's Office is a civil bureau, imed by a permanent clerical force belonging to the civil service and paid from another appropriation than the Army, although several medical officers are on duty in it in charge of divisions of the office. Surgeon-General's Office. — This office being the ad- ministrative agency by which the Surgeon-General rcises his authority and his advisory functions i- the medical service of the Army, a brief descrip- tion of it is appropriate, although as above shown it is not strictlv speaking a part of the Medical Depart- ment. Besides the medical officers detailed for duty therein, and the Superintendent of the Nurse Corps, the personnel of the bureau consists of ninety-eight clerks of various grades, seven specialist- connected with the library and the museum, and some mechanic-, messengers, laborers, et C. As shown by the diagram the office is divided into five divisions: The first under the Chief Clerk, a civilian, has charge of the general correspondence, the records, the disposition of the mail, the examinations of property and money accounts, the preparation of plans lor t he const ruction and repair of hospitals, and the control of the clerical force. The second, the Supply Division, is under a medical officer, anil has charge of the purchase and issue of medical supplies and equipment of every sort, and their accumulation for war, the administration of the depots for medical supplies, and the disbursement, of the medical and hospital appropriations, and those for artificial limbs and apparatus for pensioners. Commissioned medical officer ■ Civil official or clerK", Secretary of War Chief of Staff J Surgeon General Fia. 317. — Diagram of the Divisions of the Surgeon-General's Office. The third, the Sanitary Division, is under a medical officer and passes upon all medical questions which come to the War Department, including the recom- mendations made by medical officers in their sanitary reports. It handles also all questions of physical fitness for the military service in officers and enlisted men and reviews the proceedings of retiring boards. It tiles and collates the records of sick and wounded, tabulates the vital statistics of the army and prepares the annual report of the Surgeon-general. The fourth, the Personnel Division, is under a medical officer. It keeps the personal records of, and conducts the correspondence relating to the stations and duties of all individuals of the Medical, Medical Reserve, Dental, Nurse, and Hospital Corps, in all about 4,3(10 persons in time of peace. The fifth, the Museum and Library Division, is under a medical officer with several assistants, of which two are permanent civil appointments con- nected with the library, and another, a medical officer, is curator of the Medical Museum. This division occupies its own building at the corner of Seventh and B streets, S. W., Washington, D. C. The Museum was established during the Civil "War and contains in all more than 34,000 specimens. It is particularly rich in specimens illustrating gun-sliot injuries of the skeleton; in colored representations in wax of skin diseases; in specimens snowing the historical develop- ment of microscopes, ophthalmoscopes, stethoscopes; and in specimens illustrating the development of surgical apparatus. It has also a large collection of medals celebrating medical and hygienic subjects and events. 567 Army Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The library was developed in the years succeeding the Civil War from a small collection of books for the use of medical officers on duty in Washington into the great national institution which it is at present. It has over 175,000 bound volumes and 310,000 pam- phlets and theses. Its collection covers the literature of medicine since the invention of printing. Besides the fact that it is the largest medical library in the world its distinctive feature, which has made it famous, is the index catalogue which covers the en- tire range of medical subjects, being arranged both by subjects and authors. Osier says with reference to it "While there is not in American medicine much of pure typographical interest, a compensation is offered in'one of the most stupendous biliographical works ever undertaken. The Index-Catalogue of the library of the Surgeon-general's office atones for all shortcomings, as in it is furnished to the world a universal medical bibliography from the earliest times. It will ever remain a monument to the Army Medical Department, to the enterprise, energy and care of Dr. Billings, and to the scholarship of his associate, Dr. Robert Fletcher." (2) The medical corps consists of the following grades and numbers of medical officers besides the Surgeon-general, all of whom have the rank, pay, and allowances of officers of corresponding grades in the cavalry arm of the service: 14 colonels; 21 lieutenant-colonels; in") majors; 300 captains and lieutenants; the officers of the latter grade being promoted to the former after three year's service, provided that they have been proven proficient by passing the pre- scribed examination for such promotion. Appointments in the Medical Corps are mad. • by the President and confirmed by the Senate upon the recommendation of the Surgeon-general after the ap- plicant has passed the prescribed physical and pro- fessional examination. These examinations are rigid 'and the success of the candidate depends upon his own merits and qualifications alone, official and political influences being powerless to make good deficiencies. The candidate must be a citizen of the United States, between twenty-two and thirty years of age, must have satisfactory general education, must be a graduate of a reputable medical school legally authorized to confer the degree of doctor of medicine, and must have had at least one year's hospital training, including practical experience in medicine, surgery, and obstetrics. Th.' examination consists of two parts, a prelimi- nary and a final or qualifying examination. The former is held by boards convened at convenient places, usually military posts in various parts of the country, which make the physical examination, and then conduct the professional examination which is in writing and by questions sent to the board from the office of the Surgeon-general. Qualified applicants are then appointed to the Medical Reserve Corps, with the rank of First Lieutenant, and ordered to Washington for a course of instruction in the Army Medical School. They receive the pay and allow- ances of that grade for the journey and during the session of the school, which lasts from the first of i ictober to the last of May. This school was established in 1893 by Surgeon- general Sternberg in the City of Washington. It gives advanced and very practical courses in hygiene, sanitary chemistry, clinical microscopy and bacteri- ology, tropical medicine, the military aspects of medical and surgical practice, ophthalmology and optometry, Roentgen-ray work, medical department administration, and the military duties of medical officers, hospital corps drill, and first-aid. Lectures are also given in psychiatry with clinical instruction at the Government Hospital for the Insane, and a short course in military law by the Judge-advocate General. Instruction in horsemanship is given by officers of cavalry at Ft. Myer. The laboratories of the Army Medical School are equipped for research work as well as clinical instruction, and the facilities of the Army Medical Museum, and the Library of the Surgeon-general's Office are available for its teachers and students. Candidates who fail to reach a satisfactory standard at the qualifying examination or whose conduct or scholastic standing is not satisfactory during the term, are discharged and returned to their homes. Successful candidates are at once given commissions in the Medical Corps, if, as is usually the ca~c, vacancies exist therein, and are at once assigned to duty with troops. The pay of a First Lieutenant, Medical Corps, is $2,000 a year. He is also, as are all medical officers, furnished with a house, furniture, fuel, lights, horses, forage, and professional books and instruments. He is permitted to purchase government supplies at cost and when he travels under orders his expenses are paid and his personal property transported free of charge. At the end of three years' service he is promoted to Captain, Medical Corps, provided, however, that he passes satisfactorily a prescribed examination which is intended to demonstrate whether or not the young officer has made good use of his time and opportunities, In ease of failure in this examination the proceedings of the examining board are reviewed by a special board and if their findings are confirmed the officer -o failing is given an honorable discharge from the service with a donation of a year's pay. In this and subsequent examinations for pro- motion, if the officer is found to be physically unfitted for active service because of a disability incurred in the line of duty he is promoted and retired. In less than two years after receiving his promotion as Captain the medical officer has completed his first five years of service and becomes entitled to an increase of pay of ten per cent, and for each additional term of five years a further increment of ten per cent, is added to the pay of his grade up to forty per cent, at the end of twenty years service. These increments are colloquially known in the Army as "fogies." Pro- motion to the next grade of Major depends upon the occurrence of vacancies in the upper grades, and is theoretically assumed to occur after from fifteen to eighteen years of total service, but of late years, owing to increases in the Medical Corps from time to time, the period has in most instances been much less. The promotion to the grade of Major is after an ex- amination under similar conditions but differing in scope from that for the grade of Captain, and failure is followed by a like penalty. When the medical officer reaches" the top of the list of majors he under- goes the third and last examination for promotion, but as the duties of the next grade of Lieutenant- colonel are mainly of a supervisory and administra- tive nature, this examination is not professional in character except as regards the applications of preventive medicine and general and military hygiene, but deals largely with the important duties of Chief Surgeons. Because of the age and length of service of officers of this rank the penalty of failure is some- what different, being suspension from promotion for a year and a second trial at the end of that time. If then successful the promotion accrues, but if the officer again fails he is placed on the retired list with three-fourths of the pay of the grade of major. _ Promotion to the grade of Colonel is by seniority. The Surgeon-general is appointed by the President by selection from the officers of the Corps, but usually from the two upper grades, for a term of four years and may be reappointed for a second or third term provided he does not meanwhile reach the age of .Vis REFERENCE HANDBOOK OF THE MEDICAL SCIENI I 3 Army Medical Department (sforty-four, at which retirement from active service i compulsory by law for all offii From tin' Colonels and Lieutenant-colonels are selected tin' Chief Surgeons of militarj - and departments, tin' Chief Surgeons of the larger military commands of tin- mobile army fur sen ire in the Geld, tho commanding officers of general hospitals, and other like positions of importance and responsibility. Tin' salary of medical officers of the several grades depends somewhat upon the length of service i> i [e lint the follow inn table represents what may insidered the normal rates of pay: < ! . .riers With quarters Grade, furnished. commuted. First lieutenant V $2,432 in -'.400 2.976 in, five years' service 2,640 3,216 in, ten years' service 2,880 3.456 lin, fifteen years' service.. . . 3,120 3,696 fifteen years' service 3,900 4,620 ir, twenty years' service .... 4.000 4,720 mant-colone] 4,500 id 5,01 i 6,008 Burgeon-general 6,000 7, 1 52 Fuel and lights are furnished in kind, the allowance being iberal and increasing with each grade. The distinguishing color of the Medical Depart- ment was formerly green, but after the Spanish War in 1902 maroon was adopted because, being the dis- tinctive color of the medical service of most of the great military powers, its advantages in war were obvious. This color appears in the uniforms of all commissioned officers of the Medical Corps, Medical Reserve Corps, and Dental Corps on the shoulder straps, the collar of the full dress coat, and the band of the dress cap. The distinctive badge of the Medi- cal Department is the caduceus which is worn on each side of the collar of the service and dress coats, on the sleeve cuffs of the full dress and special evening dress coats, and the overcoats of all commissioned officers of the Medical Department. In the case of the Reserve, Dental, and Nurse Corps, the caduceus is surcharged with the monogram appropriate to each. W^ Fig. 318. — Badge oi the Medical Corps. (3) The medical reserve corps was created 1 ty t he reorganization of April 23, 1908, to take the place of the Acting Assistant Surgeons and Contract Surgeons of former days, who were civilian physicians attached to the Army but without a definite military status and authority, an anomalous and trying position, which was most unsatisfactory to members of a dignified and learned profession. They have the rank of First Lieutenants, and their commissions "confer upon the holders all the authority, rights, and privileges of commissioned officers of the like grade in the Medical Corps of the U. S. Army except promotions, but only when called into active duty and during the period of such active duty.'' An applicant for appointment in the Medical rve Corps must be between twenty-two and forty- five years of age, a citizen of the United States, and a graduate of a reputable medical school, and must pass a satisfactory physical and professional examina- tion. Examinations for appointment are held from time to time, and at lea year al convenient localities throughout the country. I he number of officers commissioned in the Medical Reserve Corps is not fixed by law and the inactive lis) is an unlimited one from which the Secretary of War may call to active duty as many as the emer- gencies of the quire. They cannot be com- pelled to accept active duty, bul should it be declined by a reserve officer his commission will lie vacated. receive 1 1 I [tenants of the Medi- cal Corps, viz., $2,000 a year with an additional $200 for each live years of active service. They receive also fuel, lights, horses, horse-equipmen) and fori when necessary, travel allowances, professional luniks and instruments, and quarters in kind or commuta- tion therefor at the rate of $36 a month. It i- tin- policy of the Medical Department to appoint each year a number of young physicians who have just pleted their medical education into the Reserve - and to give them at once a tour of active service of from six months to two years in order that they may become familiar with the conditions and admin- istrative methods of the Army medical service. De- tailed information as to the physical and professional requirements for appointment can be obtained upon request of the Surgeon-general. The uniforms, side arms and equipments of Medical Reserve officers are like those of the .Medical Corps with the difference only that the caduceus bears the letters " R. C." superimposed in monogram. Fig. 319. — Badge of the Medical Reserve Corps. (4) The dental corps was created by the Act of March 3, 1911, and consists of Dental Surgeons and Acting Dental Surgeons, the total number of which together cannot exceed the proportion of one to each thousand of the actual enlisted strength of the Army. All original appointments to the Corps are made as Acting Dental Surgeons after passing a satisfactory physical and professional examination before a board composed of a medical officer and two dental surgeons. Applicants must be citizens of the United States between twenty-one and twenty-seven years of age and graduates of a standard dental college. Acting dental surgeons who have served in a satisfactory manner for three years are eligible, after passing a satisfactory professional and physical examination, to be commissioned as First Lieutenants in the Dental Corps. Lieutenants of the Dental Corps rank next after the Medical Reserve Corps and have the same pay and allowances as the latter, including the quin- quennial increase for length of service, in computing which service as an Acting Dental Surgeon is counted. Dental Surgeons on attaining the age of sixty-four are retired from active service with the pay of three- fourths of their grade including the increase for length of service. Their right to command is restricted to the dental corps. The uniforms of commissioned dental surgeons are the same as those of medical officers of like grade, with the exception that the caduceus bears the letters " D. C." superimposed in monogram. Acting dental 5G9 Army -Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES surgeons are not required to have the full dress uni- form but only the dress, service, and white uniforms which conform to those of medical officers, but with- out the shoulder strap or other insignia of rank. Their pay is at the rate of $150 a month with fuel, lights, quarters in kind, and travel allowances. They do not receive the increase of ten per cent, for each five years of service but as above stated their service counts therefor when commissioned. Fig. 320. — Badge of the Dental Corps. (5) The aemt nurse corps was created by the act of February 2, 1901, and amended by that of March 3, 1910, by which a definitestatus was given to graduate female nurses who before had been employed under contract for service in the Army but had not been an established part thereof. At its head is a superinten- dent who, under the direction of the Surgeon-general, has general supervision of the Corps, her office being a part of the Personnel Division of the Surgeon-general's Office. The Corps is composed of Chief Nurses, nurses and reserve nurses, in such number as may be needed for the military service. The number of Chief Nurses and nurses in active service is 125. They are stationed only at General Hospitals and a few of the larger post hospitals. Chief Nurses are appointed from members of the Nurse Corps by the Surgeon-general, upon the recommendation of the Superintendent, and after a satisfactory examination, one being stationed at each hospital or station where nurses are on duty. Applicants for appointment in the Nurse Corps are required to be graduates of acceptable training schools, having a theoretical and practical course of not less than two years and attached to a general hospital of not less than 100 beds. They must pass satisfactorily a physical examination, preferably made by a medical officer and a professional examination conducted by the Superintendent. Appointments are made for three years and are renewed upon application by the nurse if her service has been of a satisfactory char- acter. The list of Reserve Nurses of the Army, contem- Fig. 321 — Badge of the Red Cross Nurses. plated by law, and consisting of honorably discharged our es, has not been carried out, because one of the functions of the American Red Cross is to furnish the Medical Department of the Army in time of war or other emergency with nurses and other personnel. In order to be able properly to meet this obligation the Red Cross has enrolled an eligible list of over 3,000 carefully selected graduate nurses, and these now constitute the reserve of the nurse corps. They will be called into service through the central office of the Red Cross with their own consent, and will then be subject to the same regulations and receive the same pay and allowances as permanent members of the Nurse Corps. The pay of the Superintendent is $1,S00 a year, with the same allowances as other nurses. The pay of nurses begins at S50 a month when serving in the United States and increases at the rate of ten per cent, for each three years of service up to $05 for over nine years' service. To this is added .$10 a month for service outside the continental limits of the United States. Chief Nurses receive $30 a month additional when in charge of the nursing service at general and base hospitals, and in hospital ships. Other chief nurses get $20 a month in addition to their pay except when on duty where special skill and capability are required, when the Surgeon-general may increase the amount to $30 a month. Thus while a nurse who has just joined at a hospital in the United States gets $50 a month, the Chief Nurse at the base hospital at Manila may receive $105 a month. They receive also quarters, subsistence, travelling expenses when travelling under orders, leave of absence on full pay for thirty days in each year, which may be cum- ulative up to four months. The quarters provided for nurses are usually detached from the hospital, and include a sitting- room, dining room, kitchen, the necessary toilet rooms and a separate bed room for each nurse. When more than five nurses are on duty at a hospital the Chief Nurse is entitled to an office and a separate sitting-room. The furniture, equipment, and service of nurses' quarters is furnished by the Medical Depart- ment, which also provides the laundry service for table and bed linen and nurses' uniforms. The uniform of the Nurse Corps which is always worn when on duty consists of a waist, belt, and skirt of suitable white material, bishop collar, and a white cap made according to specifications prescribed by the Surgeon- general. The badge of the Corps which is worn on the left side of the collar is a caduceus of gold or gilt with the letters "A. N. C." in monogram super- imposed in the center. Fia. 322. — Badge of the Army Nurse Corps. The history of expert nursing in the Army is of recent date, since trained nursing as a profession was not introduced into this country until 1S73. Women have since the early days of the republic been em- ployed in the care of the sick, but the duties of the humble predecessors of the present nurse corpswere quite different from those of their accomplished sisters of to-day, and are now relegated to the hospital orderlies'. The Army Regulations of 1S14 provide " (3) Every regimental hospital shall be supplied with 570 IM'.FERENCE HANDBOOK OF THE MEDICAL SCI] NCES Army Medical Department one or more fciiialc attendants; it shall he the business df these lii scour and cleanse the bunks and II -s of the rooms or tents, to wash the blankets and bed sacks and clothes of the patients, to cook the victuals of the sick, and to keep clean and in good order the inn utensils." The functions of the women nurses in the Civil War were of a much less menial .ntcr and except for lack of .scientific training approached those of the graduate nurses of a later day. An authority* on this subject slates thai "the Civil War marks the beginning of all organized concentration of women in this country in public duties." It is estimated that 2,000 women were engaged in nursing ami hospital administration during the Civil War. Miss Dorothy L. Dix was lOinted superintendent of women nurses in general hospitals in 1862, and it was ordered that except in emergency no women should be employed as nurses without her approval. No candidate for position as nurse was considered unless she was between the age of thirty-five and fifty; matronly us of experience and those of superior education and superior disposition were to have the preference. Habits of neatness and order, sobriety and industry were essential. Medical officers were required to organize their hospitals so as to have one woman e lor every two men nurses or attendants. In the forty-three years between the termination of the Civil War and the outbreak of the Spanish War nursing as a profession had become well established in the United States and trained nurses of excellent attainments were employed in large numbers by the Medical Department of the Army. Through a miscarriage in the legislation authorizing the calling out of volunteers, authority was not given for the enlistment of a volunteer hospital corps, and it was impossible to obtain a sufficient number of men of good character and capacity by enlistment in the Hospital Corps of the regular army. The vacancies were filled, therefore, by the clumsy expedient of transferring the least desirable men who were not desired by their company and regimental commanders from the volunteers to the regular hospital corps. The results were most unsatisfactory until the employment of trained nurses in large numbers brought order, neatness, and efficiency into the wards of the general hospitals. At the beginning of the Spanish War the Surgeon- general was authorized to employ nurses under contract and an appropriation was made for their pay. No restriction as to sex was made but as the supply of trained nurses in the country was almost entirely female and as their services were intended to be restricted to the general hospitals, where proper provision for the comfort and privacy of women could be made, the number of men nurses employed instead of being double that of the other sex, as in the Civil War, was so small as to be negligible. At the beginning a few untrained women were employed especially for the purpose of getting immunes to care for the cases of yellow fever which had occurred in the Army in Cuba, but soon thereafter the national society of the Daughters of the American Revolution offered to take charge through committees, of the selection of those of proper qualifications and char- icier, and this offer was promptly accepted by the ^con-general. Dr. Anita Newcomb McGee was appointed director of the board designated for this purpose and was later appointed an acting assistant surgeon, and assigned to duty in the office of the Surgeon-general to act upon all matters relating to Army nurses. The committee of women which was auxiliary to the American National Red Cross Relief Committee of New York also examined and certified a large number of nurses as suitable for employment in the Army, besides paying the expenses incident * A History of Nursing, by M. Adelia Nutting and Levina A. Dock. In their arrival al their places of assignment to duly. More than 200 sisters of charily were also furnished by religious orders. One thou and live hundred and sixty-three nurses in all were employed under con- tract by the Medical Department. (0) The hospital coeps. of the Army was created by the Act of March 1, ls.sT (24 Stats., 135), before which lime the attendance in military hospitals was supplied by details from the line of the Army and by hired civilians. The unsatisfactory character of this service will be referred In later. The act above referred to provides: "That the Hospital Corps of the United States Army shall consist of hospital stewards, acting hospital stewards, and privates; and all necessary hospital services in garrison, camp, or field (including ambulance service) shall be performed by the members thereof, who shall be regularly enlisted in tin; military service; said corps shall be permanently attached to the Medical Department, and shall not be included in the effective strength of the Army nor counted as a part of the enlisted force provided by law." This law was amended by the Ad of March 2, 1903, so as to increase the number of grades in the corps and alter their titles from hospital stewards, acting hospital stewards, and privates to sergeants, first class, sergeants, corporals, privates, first class, and privates. This act also authorized the organization of companies of instruction, ambulance companies, field hospitals, and other detachments in the Hospital Corps as the necessities of the service may require. Acting cooks and lance corporals have been also added as separate gradings. The corps is recruited by enlistments therefor and by transfers from other branches of the service. All first enlistments and transfers are to the grade of private. The strength of the Hospital Corps is not limited by law, but the Secretary of War is authorized to enlist or cause to be enlisted as many privates of the Hospital Corps as the service may require, it being clearly the intention of Congress to place upon the War Department the responsibility for any suffering which may be caused to the sick and wounded, or any inefficiency of the medical service, which may result from a deficiency of enlisted personnel. The numbers and pay of the various grades of the Hospital Corps are shown in the following table: Sergeants, 1st Class Sergeants Corporals* Acting eooksf Privates, 1st Class.. Privates Num- bers. 330 350 50 100 1,867 963 Enlistment. 1st, IM. S50 $54 If re-enlisted within three months. 3d. HI. $58 Sr,L> 5th. J6th. 7th. Sfifi S70 S74 42 36 42 30 24 4S 4 J 48 36 26 If discharged at termination of enlistment and re-enlisted after three months the soldier is only entitled to pay of second enlistment. It is required that the proportion of privates, first class, to privates shall not exceed two to one. Cor- porals are appointed for duty in ambulance com- panies, and in the larger hospitals for duty principally of an outside character. Promotion to the grade of sergeant is made after an examination by a board of * Lance Corporals are not properly a distinct grade, being simply privates who are given the temporary duties and authority of corporals, without any increase in pay. t Acting cooks are detailed from privates, first class, and privates. 571 Army Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES medical officers, which reports upon the candidate's qualifications as to his physical condition, character and habits, discipline and control of men, knowledge of regulations, of nursing, of dispensary work, of cleri- cal work, of the principles of cooking and mess management, of hospital corps drill, and of minor surgery and first aid work. Married men are not eligible for promotion. Chief Surgeons are authorized to hold these examinations without reference to the Surgeon-general. Examinations for appointment to Sergeant, First Class, are conducted by boards of medical officers ap- pointed by the General Commanding the Division. The examinations therefor are oral, practical, and written. They embrace the same subjects as for the grade of sergeant, but are more difficult. Sergeants, first class, are required to have served not less than twelve months as Sergeants before being eligible for promotion. The Sergeant, First Class, ranks with the Ordnance Sergeant, Post Commissary Sergeant, Post Quarter- master Sergeant, First Class Signal Sergeant, and Electrical Sergeant, First Class, of the Coast Artillery, and is only ranked by Sergeants Major, Master Electricians, Chief Musicians, and Engineers of the Coast Artillery. The duties of Sergeants, First Class, and Sergeants are to look after and distribute hospital stores and supplies, the care of medical property, to compound and administer medicines, to supervise the prepara- tion and serving of food, maintain discipline in hospi- tals, prepare reports and returns, supervise the work of their subordinates, and perform such other duties as may be required of them by their superior officers. No other noncommissioned officer requires so much special knowledge for the proper discharge of his duties or has such a variety of duties to perform as the Sergeant, First Class, Hospital Corps. Like the First Sergeant of a company he must be a good dis- ciplinarian, drill master, and general supervisor of the duties of the men under his control. He pre- pares or supervises the preparation of numerous reports, returns, and other official papers, some of them voluminous and complicated, which must be made not only to the Surgeon-general, but to the adjutant of the command, the Adjutant General of the Army, and to the officials of the Quartermaster and Commissary Department. He must keep track of, and prevent waste of a great number of articles in- cluded under medical and hospital property; he must be a pharmacist and have sufficient knowledge of medicine and surgery to act as an assistant to the medical officer. It is commonly supposed that skill in pharmacy is the essential qualification of noncom- missioned officers of the Hospital Corps, but from the enumeration above it will be seen that knowledge of drugs is only one of the many qualifications which are demanded of them. One of the most important duties of medical officers is the instruction of the Hospital Corps to which a certain number of hours every week throughout the year is given, and which never ceases so long as the soldier is in the service, in connection with his daily round of duties. The instruction of the Hospital Corps soldier covers the Articles of War, the orders and regulationsin regard to his behavior and bearing upon all occa- sions, bearer drill and field work, use of the first aid packet and other articles contained in the hospital corps and orderly pouches, methods of transporting wounded in peace and war, the use and care of the field hospital equipment, and the pitching, striking, and packing of tents. All members of the Hospital Corps arc also instructed in riding and in the care of animals. They are also instructed in military sanita- tion, especially in the purification of water and proper di posal of excreta and wastes, and the care of the person. In the field when serving with infantry or other 572 troops not mounted, only the noncommissioned officers are mounted and the privates who serve as orderlies for medical officers, the latter carrying in- stead of the hospital corps pouch an orderly pouch which contains a pocket operating case, hypodermic syringe, scissors, catheter, and ligature material, in addition to first aid dressings. The equipment of privates of the hospital corps consists of a hospital corps pouch containing first aid dressings, a large hospital corps knife, carried in a scabbard like a sword, and used for various purposes in the field, a haversack and blanket roll, canteen, cup, knife, fork, spoon, meat can, and a shelter tent, half which is on the march rolled about the blanket and in camp is joined to the tent-half of a comrade to make the shelter tent for the two men. The clothing allowance of the Hospital Corps is liberal, amounting to $142.44 for the first enlistment, and $103.61 for each subsequent enlistment. The value of all clothing not drawn is paid to the soldier upon his discharge. They are required to have four uniforms: a field uniform of khaki and one of olive drab; a dress uniform of dark blue, to which is added on occasions of ceremony a maroon breast cord, and a blue and maroon cap band; and a uniform of white duck, to be worn by men on duty in the wards, dispen- saries, operating rooms, mess rooms and kitchens, and by privates who are detailed as assistants to dental surgeons. The overcoat is of olive drab like that of the line. The distinctive color of the facings of the Hospital Corps is the same as for the other personnel of the Medical Department, maroon, which is however piped with white to distinguish it further from the shade of red adopted for the artillery, which is scarlet. The maroon facing appears on the chevrons and trouser stripes of the noncommissioned officers, on the piping of the dress coat and mixed with white in the breast collar, and the dress and the hat cord of the service uniform. The corps insignia are worn on the coat collar, and the dress and service cap. They are: For the dress coat a caduceus of yellow metal, similar to those for officers, worn on the collar on each side in the same manner as by officers; For the service coat a caduceus of dull bronze worn as above stated; For the dress cap, for Sergeant, First Class, a cadu- ceus of white metal enclosed in a wreath of gilt metal, and for all other men of the Hospital Corps a caduceus of gilt metal without the wreath; For the service cap these insignia are of dull bronze. Fig. 323. — Chevron of a Sergeant, First Class, Hospital Corps. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Department 7 The clerical force at large ami other civilians attached to the medical corps includes the clerks, engers, mechanics, and laborers employed al I he ii.-al supply depots in Washington, New York, Louis, San Francisco, and Manila, the clerical force of the offices of the Chief Surgeons, Headquar- ters of the four great territorial divisions, and the mechanics and laborers, with a few clerks, at the eral hospitals. It will be observed that the clerical force of the Surgeon-general's t Iffice is not included, as it is, as stated above, a part of the War Department, which is one of the executive departments and quite distinct from the Army. The total number of clerks employed at the stations above named is forty. ging in salary from $'2,000 to $(>()(). There are employed sixteen packers and four mechanics al annual salaries ranging from $1,200 to $780, The ■I number of employees, including the variable number of laborers, was on January 1, 1912, two hundred and thirteen, with a total pay roll of about $140,000. Historical Resume. — The Medical Department of the United States Army had its beginning on July 27, 177", when the Colonial Congress at Philadelphia 1 a medical establishment, or as it was then railed, "an hospital," for the Army. Prior to this tment the surgeons of the forces before Boston been appointed by the colonels of regiments, with the wise proviso, however, on the part of the Provin- cial Congress of Massachusetts that they should be examined by a medical board named by the Provincial gress. That there was nothing pro forma in these examinations is shown by the fact that no less than six of a group of fourteen were rejected on account of failure to come up to the standard. After the battle of Bunker Hill a field hospital was estab- I at Cambridge for the care of the wounded. Subsequently general hospitals were established at Ticonderoga, X. Y., and at Williamsburg, Va. To provide these with the requisite medical officers surgeons were appointed who belonged to no regi- ment, but to the hospital department in general as staff surgeons. Tills arrangement aroused a strong feeling on the part of the regimental surgeons who protested against the removal of their sick, and their reduction to the level of dispensary surgeons for the -lighter ailments of camp. They claimed the right to take care of their own sick and they were supported in this by a majority of the regimental and company officers. It is interesting to observe how mankind 'ts its experiences. More than 120 years after- ward during the Spanish-American War the same clamor was raised by regimental surgeons of volun- teers, their colonels and company officers, against the establishment of division hospitals, and the necessary disestablishment of regimental hospitals as incompetent to meet the exigencies of active field service, although this incompetency had meanwhile been proved during the long years of the Civil War. Of course, among these surgeons there could be no -ion or effective cooperation, and, as General Washington wrote to the Congress at Philadelphia, affairs were in a very unsettled condition. "There is no principal director nor any subordination among the surgeons; of consequence, disputes ami conten- tions have arisen, and must continue until it is reduced to some system." The first department consisted of the director general and chief physician, four surgeons, twenty surgeons' mates, an apothecary, a clerk, two store- keepers, and a nurse to every ten sick. It may be of interest to mention that the pay of these officers was as follows: The director general, $120; the surgeons, the surgeons' mates. $20; the storekeepers, $4, and the nurses, $2 a month. Dr. Benjamin Church of Boston was elected director general, and he was given the appointment of all the personnel of the hospital, except the surgeons' males, « i,,, were appointed by I he surgeons. Dr. church had a reputation for culture and profes- sional skill, but was a few month- after hi- appoint- ment detected in treasonable correspondence with the enemy, deposed and thrown into prison. He was succeeded by Dr. John Morgan of Philadelphia a man of much energy and administrative ability as well as professional skill. He soon gained I he friend- ship and support of General Washington, and the B he always retained. Willi the extension of the theater of war, the number of surgeons was increased, and Drs. Skinner and Shippen were named chief surgeons for the northern department and the forces on the west bank of the Hudson. The organization was, however, too loose to secure efficiency or concert of action. The relations of the regimental surgeons to each oilier and to those in charge of the general hospitals were entirely undetermined, and the department surgeons refused to admit the authority over them of Dr. Morgan. There was beside no well-arranged sys- tem of medical supply, and in consequence there was much suffering, and complaints multiplied. As has happened since, more than once, Dr. Morgan was punished for the very shortcomings for which he had in vain asked Congress to provide a remedy, and he was dismissed in January, 1777. Congress' the next year exonerated him from all blame, but did not reinstate him. A complete and elaborate organization of the medical department, modeled on that of the British tinny, was adopted in April, 1777, and Dr. William Shippen was elected director general of the new establishment. Deputy director generals were pro- vided for the northern and southern departments, and under these a physician general and surgeon general in each district, "whose business it shall be to super- intend the practice of physic and surgery in all the hospitals of the district." This separation of the practice of physic and the practice of surgery, which obtained in Europe at that time, and has fasted in civil life in England until the present dav, neces- sitated a most cumbrous and awkward dual organiza- tion, which soon disappeared under the rudely prac- tical test of war. It is probable that most American physicians at that time outside the larger cities practiced surgery to some extent, in addition to the practice of physic. The regimental surgeons seem from the first to have combined the two arts, and we find in the bill, which in 1780, reorganized and simplified the medical establishment, an explicit provision that "there shall be three chief hospital physicians who shall also be surgeons, one chief physician, who shall also be a surgeon, to each separate army, fifteen hospital physicians who shall also be surgeons," etc. But although the medical officers of the army thereafter appeared to have been both physicians and surgeons, the former title seemed to have been rather reserved for the higher grades, while the title "surgeon" became bv the end of the Revolutionary War generic for alPmedical officers. At the end of the Revolution the Army was dis- banded, except fifty-five men at Ft. Pitt and twenty- five at West Point to guard the military stores at these places. The officer highest in command was a captain, and the medical department was reduced to the vanishing point. The Revolution had pro- duced a number of distinguished military surgeons, among whom were Cochran, John Warren, Craik, and Tilton, in addition to those already named. The pressure of Indians on the western frontier after a few years prevailed over the morbid fear of a regular army with which our ancestors of a century ago were possessed, and in 17X0 a regiment of regular infantry and a battalion of artillery were organized, with a medical service of one surgeon and four sur- geons' mates. This small force was divided up into a 573 Army Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES number of small commands at scattered posts along the frontier and the regimental surgeons were entirely too few in number to supply them. In 1802, there- fun-, a new departure was taken in the employment of post surgeons in addition to the regimental medical officers. If general hospitals were established sur- geons of a higher grade and rate of pay than the regular post surgeons were appointed for temporary service. In this way the medical department was enlarged to meet the necessities of the Army in the year 1912. The War of 1S12 brought an army again in the field, but as the medical department was without a head and the surgeons had not even assimilated rank, good medical administration was impossible. In March, 1S13, Congress created the positions of physician-and-surgeon-general and apothecary gen- eral, the latter to act as assistant to the former, and as medical purveyor. The surgeons were divided into hospital and regimental surgeons, of which the former were superior in rank and pay. Both had mates and assistants, and there were in addition post surgeons who ranked with the mates. Dr. James Til ton who had been a hospital surgeon during the Revolution was appointed physician-and-surgeon- general in 1S13. His management of affairs during the war appears to have given universal satisfaction. Many hospitals were established and broken up during the course of events, but all appeared to have been well administered and well supplied and competent for the work thrown upon them. Some indeed as that at Burlington, Vt., under the superintendence of Surgeon Joseph Lovell, Ninth Infantry, appear from the reports to have been model establishments. The title of surgeon-general appears first in the Act of May 14, 1818. Joseph Lovell was appointed to this position, and in that year he made the first annual report of the surgeon-general to the Secretary of War, and also drew up a set of regulations for the medical department. He remained for eighteen years at its head and during that time by his ability and force of character shaped and organized the corps of army surgeons into a coherent and efficient medical staff. In 1821 a further advance was made in the organization of the department by consolidating the regimental surgeons with the staff surgeons so that the corps consisted simply of one surgeon-general, eight surgeons with the rank and pay of regimental surgeons, and forty-five assistant surgeons with the pay of post surgeons. This number, however, was insufficient to provide one medical officer to each of the military posts, and so the system of employing certain physicians under contract was instituted. Surgeon-general Lovell died in 1836. The medical department was fortunate in having so able a man as Dr. Lovell appointed as its chief. He defined the duties of his subordinates, established an excellent system of accountability for property, improved the medical reports, inspired his officers with the idea that as sanitary officers they had greater responsibilities than mere practising physi- cians and surgeons, and labored earnestly to have their pay increased and their official status raised in proportion to his views of the importance of their duties. He also established an equitable system of exchange of posts so that no officer would be retained unduly at an undesirable station. He was succeeded by Thomas Lawson, a man of strong character and fine professional and administra- tive abilities, and withal a brave and ardent soldier, and a most original character. He entered the Navy in 1809 as surgeon's mate, but left that service for the Army in 1811. His service as a medical officer of the Army covered the remarkable period of fifty years and three months, and included active and distinguished set-vice in the War of 1812, the Indian Wars, and the Mexican War. At the outbreak of the latter he turned over the office in Washington to an assistant and joined his old friend Gen. Scott with whom he made the campaign, performing the duties of Chief Surgeon in the field, for which his long experience so eminently fitted him. When he became surgeon- general, in 1S36, medical officers were without mili- tary rank, and in addition to the great disadvantages of such a status, suffered frequently from the insolence and contempt with which the line officers of that day. following the traditions of the British service, were inclined to regard the medical profession. Surgeons, for example, were not entitled to a salute from enlisted men, and when serving on boards were ranked by the youngest subaltern in the service. In the new uni- form, adopted in 1839, they were allowed a s^ord, but not the officer's epaulettes, an aiguilette being prescribed instead; "a piece of tinsel on one shoulder," as Lawson contemptuously described it. To establish and maintain the dignity of his pro- fession and his corps, was to Thomas Lawson a sacred mission, to which he devoted himself with such courage, pertinacity, and keenness of wit that he achieved success in all the important claims advanced in behalf of his corps, culminating in the Act of February 11, 1847, which conferred on medical officers the assured and honorable status of definite military rank. It is a tradition in the service that on the passage of this act the grim old fighter sent around to medical officers a confidential circular to the effect that now that the}' had the status of officers they must promptly challenge any other officer who failed to show them proper respect. During the Mexican War the senior surgeons were assigned as medical directors and in charge of field hospitals. Certain of the juniors were on duty at the hospitals and purveying depots, while others served in the field as regimental officers with regular troops. Volunteer surgeons were on duty with their regiments but some of them were occasionally detailed to hospital duties. The medical service of the Mexican War seems to have been performed with the same efficiency, courage, and devotion to duty which marked all the operations of the small but glorious armies under Scott and Taylor, and such men as Satterlee, Tripler, Simpson, Cuyler, Wright, Moore and Barnes laid in it the foundation of reputations which were destined to grow under the far wider responsibilities of the Civil War. In the fierce assault of Molino del Rey, Assistant Surgeon William Roberts was killed and Assistant Surgeon James Simons was wounded. Although the Army Regulations for 1S25 contained a clause that no person should receive the appoint- ment of Assistant Surgeon until after examination by a properly authorized board, yet this rule was not at first carried out on account of the difheultv of detailing medical officers for this purpose. It is stated that Dr. Charles Tripler, appointed an Assistant Surgeon in 1S30, was one of the first officers examined under this provision. General Orders No. 5S of the War Department, dated July 7, 1832, reiterated this regulation and directed that hereafter it should be strictly enforced, and the regulation has been steadily maintained since that date, even in time of war. This regulation was embodied in the law by the Ait of June 30, 1834, which not only required that candidates before being appointed, should "have been examined and approved by an Army medical board," but also required that an examination be held prior to promotion fo the grade of Surgeon. The thirteen years which intervened between the Mexican War and the outbreak of the Civil War were years of activity and progress for the medical corp-. although the Utah Expedition against the Mormons in 1858 was the only military event of note. \n important advance in the standard of the examina- tion for admission was made in 1849, when a knowl- edge of Latin, of physics, of practical anatomy inthc form of dissection, and clinical experience acquired 574 KF.FF.KIMT. HANDBOOK OF Till: MFDIOAL SCIENCES Army Medical nopartmcnt cither in a hospital or in private practice were made prerequisites. In lN;jO tin- Medical Department of \nny was first formally represented at the animal ting of the American Medical Association. Surgeon-general Lawson died in L861, shortly be- fore the outbreak of the Civil War. From the calls fur large levies of troops and the feeling North and h thai a desperate struggle was before the eoiin- ii was evident that without la rue reinforcements the medical department would be unable to do its work icessfully. At this time it consisted of one sur- Q-genera] with the rank of colonel, thirty .surgeons • ill the rank of major, and eighty-three assistant eons with the rank of first lieutenant and of tin after five years' service. In August, 1861, the 1 1 in n of ten surgeons and t wenty assistant surg s authorized. Some 1 of this small staff corps look irge, as medical directors, of corps and armies, ructing the volunteer officers in the duties per- taining to camps and field hospitals; others acted as medical inspectors, aiding the directors in their work of supervision and education; some organized general utals for the sick that had to be cared for on every of the armies, while others kept these hospitals and the armies in the field provided with medical and iial supplies. The remainder were assigned to service with the regular regiments and batteries. Bach volunteer regiment brought with it a surgeon and two assistants appointed by the governor of the e after examination by a State medical board. The senior regimental surgeon of each brigade became invested with authority as brigade-surgeon on the staff of the brigade commander, but as seniority in many instances was determined by a few days or -. it often happened that the best man for the don was not secured by this method. Congress •fore authorized a corps of brigade surgeons of volunteers, who were examined for the position by a hoard of regular medical officers. One hundred and ten of these brigade surgeons were commissioned. The Civil War was the first in which large armies made their appearance on American soil, and in these army corps of volunteers many of the glorious raditions and hide-bound prejudices of the old Army disappeared along with its regiments and batteries. Yet it was none the less the leaven hid in three meas- ures of meal, which leavened the whole lump, and this is true not less of the Medical Department than of the line. On January 1, 1861, the Army numbered 16,400 and the medical officers 115, or seven-tenths of one per cent, of the whole — a considerably greater propor- tion, by the way, than exists to-day. In April, 1862, a bill was passed by Congress to meet the pressing needs of the medical department. This gave the regular army an addition of ten surgeons and ten assistant surgeons, and provided for a temporary i lease in the rank of those medical officers who were holding positions of great responsibility. It gave the surgeon-general the rank, pay, and emolu- ments of a brigadier general; it provided for an assist- ant surgeon-general and a medical inspector general of hospitals, each with the rank of colonel, and for eight medical inspectors with the rank of lieutenant colonel. These original vacancies were filled by the President by selection from the army medical officers and the brigade surgeons of the volunteers, having re- I to qualifications only, instead of to seniority or previous rank. At the end of their service in these positions, officers of the regular force reverted to their former status in their own corps with such promotion as they were entitled by the casualties of the service during their temporary occupancy of these war posi- tions. About the time of this enactment Surgeon- general Finley, Lawson's successor, was retired at his own request after forty years' service, and Assistant Surgeon William A. Hammond was appointed the first surgeon-general with the rank of brigadier gen- eral, in December following eight more inspectors were authorized. Their duties were to supervise all that related to the sanitary condition of the army, whether ill transports, quarters, or camps, as will as the hygiene, police, discipline, and efficiency of field and general hospitals; to See that all regulations for protecting the health of the troops and for the careful treatment of the sick and wounded were duly ob- served; to examine into the condition of supplies and the accuracy of medical, sanitary, statistical, military, and property records and accounts of the medical depart nieut ; to invest igate t he causes of dis- ease and the met hods of prevent ion. They were re- quired also to be familiar with the methods of the subsistence' department, in all that related to the hospitals and to see that the hospital fund was judiciously applied. Finally, they reported on the efficiency of medical officers, and were authorizci to discharge men from the service on account of disability. Shortly after this the corps of brigade surgeons was reorganized to give its members a position on the general staff similar to that of the army medical officer and to render their services available to the surgeon-general at any point where they might be most needed, irrespective of regimental or brigade organizations. They henceforth became known as the corps of surgeons and assistant surgeons of volun- teers; and the appointment of forty such surgeons and one hundred and twenty assistants was authorized. The medical history of the Civil War marks an epoch in military sanitary organization even greater than was made in the art of war by Sheridan's use of cavalry or the hasty entrenchments of Lee. It is a glorious chapter of American history, but the full story of the ability and devotion of the surgeons of the Civil War, regular and volunteer, must be sought, not in the limits of an article, but by those who have industry and good eyesight, in the ponderous volumes of microscopic print which make up the " Medical and Surgical History of the Rebellion." For many years, during and after the revolution, the selection of the personnel of hospitals was left to the surgeons in charge. The stewards and ward masters, nurses and cooks were either detailed soldiers or civilians at the option of the surgeon. The Army Regulations of 1S21 for the first time distinctly provided that cooks and nurses in hospitals should be taken from the privates of the army, although such had doubtless been the usual practice before that date. During the Civil War civilians, both men and women, were largely employed as nurses, especially in the general hospitals. They may also have been employed to a limited extent in the war with Mexico. With these exceptions, hospital attendants were obtained, from 1821 until the organization of the hospital corps in 1887, wholly by the detail of soldiers of the line, an arrangement which was always unsatisfactory, for it was difficult to secure the best men of the command for such duty, and the length of the detail being uncertain and pro- motion practically unknown, there was little to stimulate the ambition of the attendant. The employment of civilians as hospital stewards for post and regiments, as well as for general hospitals, was still authorized in 1821; but as in the Indian wars which resulted from the spread of civilization westward, the activity of the army was transferred to the frontier, it no doubt became increasingly difficult to hire suitable civilians, while experience showed that it was desirable that the incumbent of this position should be amenable to military discipline and held to a definite term of service. It therefore soon became the rule that hospital stewards should be detailed from the line, as is shown by the fact that in 1S33 an order from the War Department gave authority for the enlistment of a hospital steward at posts where a suitable man 575 Army Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES could not be obtained from the command. But even though specially enlisted as hospital steward he was still mustered with a company and regarded as a detailed soldier of the line, and in 1842 the adjutant- general decided that in case of emergency he could be required to perforin military duty as such. Since the hospital steward could be returned to the line at any time at the caprice of the commanding officer, the necessity of securing for him a more permanent status was felt, and Congress in 1856 authorized the appointment of hospital stewards from the enlisted men of the army who should be permanently attached to the medical and hospital department. Command- ing officers were, however, still permitted to detail, upon the recommendation of the medical officer, a soldier to act as hospital steward for field duty or at stations where there was no hospital steward. These men were at first known as acting hospital stewards. After 1S64 they were called hospital stewards of the second class if detailed for duty at posts of more than four companies, and hospital stewards of the third class if at posts of four or less companies. In 18(52 the employment of civilians as cooks and nurses in the general hospitals having been authorized, the surgeon-general published regulations for the "Hospital Corps, U. S. Army," which was to be composed of civilians hired under contract for the period of one year, unless sooner discharged. Except in name this organization bears no resemblance to the present hospital corps, which was created by the act of Congress, March 1, 1NS7. The idea of medical organizations in the field, drilled and trained to gather up the wounded from the battle- field, transport and care for them, developed by Larrey and Percy in the Napoleonic wars, had perished with the armies of the First Empire under the retroactive prejudices of the old monarchies, and the military taboo of even republican America forbade a physician to exercise the sacred function of "com- mand over trained enlisted assistants of his own department or even to have a permanent and un- questioned jurisdiction over the mules and drivers of the medical ambulances. He controlled in battle his own two hands, and these only, unless the colonel saw fit to give him the uncertain and doubtful assistance of the regimental band. The following letter taken from the files of the Surgeon-general's Office permits a glimpse of the tragic results of this lack of an organized enlisted personnel for the Medical Department: SfrtGEON-GENERAL's Office, Sept. 7, 1SG2. Honorable Edwin M. Stanton, Secretary of War. Sir: I have the honor to ask your attention to the frightful state of disorder existing in the arrangement for removing the wounded from the field of battle. The scarcity of ambulances, the want of organization, the drunkenness and incompetency of the drivers, the total absence of ambulance attendants are now working their legitimate results, results which I feel I have no right to keep from the knowledge of the department. The whole system should be under the charge of the Medical Department. An ambulance corps should be organized and set in instant operation. I have already laid before you a plan for such an organization, which I think covers the whole ground, but which I am sorry to find does not meet with the approval of the general-in-chief. I am not wedded to it. I only ask that some system may be adopted by which the removal of the sick from the field of battle may lie speedily accomplished and the suffering to which they are now subjected be in future as far a |i< issible avoided. I p to this date six hundred wounded still remain on the battlefield in consequence of an insufficiency of ambulances and the want of a proper system for regulating their removal in the Army of Virginia. Many have died of starvation, many more will die in consequence of exhaustion, and all have endured torments which might have been avoided. I ask, sir, that you will give me your aid in this matter, that you will interpose to prevent a recurrence of such consequences as have followed the recent battle, consequences which will inevitably ensue on the next important engagement if nothing is done to obviate them. I am, sir, very respectfully, Your obedient servant, William A. Hammond, Surgeon-General. Yet even this picture of the COO men who had lain ten days on the battlefield of Second Bull Run could not bring the commanding general to lift the taboo and approve of enlisting men for the Medical Depart- ment. But while the Surgeon-general was vainly struggling with the prejudices of Gen. Halleck, light had broken in another quarter. July 1, 1862, Surgeon Jonathan Letterman reported to General McClclIan to be medical director of the Army of the Potomac He was only thirty-eight years old, having entered the service in 1849, and had just received his pro- motion to major. The Army of the Potomac was at this time crowded with sick and with the wounded of the seven day's fight, and in the retreat to Harrison's Landing most of the medical equipment and supplies had been lost or expended. In the course of a month he brought order out of this chaos, and at the same time drew up a plan for an ambulance corps — simple, far-reaching and effective — which General McClellan was quick to adopt. The personnel for this corps was obtained by transfers of officers and men from the line, and they, as well as the ambulances and other transportation, were placed entirely in the hands of the medical directors of the several army corps. A distinctive uniform and a simple drill were prescribed. This organization was announced in orders apparently without reference to Washington on August 2, and was soon followed by a scheme for regimental medical service and the establishment of division field hospitals in October. These taken together made a complete workable system, which at once made a new epoch in medical organization, and placed the Army of the Potomac far ahead of any military establishment in the world in this respect. Meanwhile the system had its first trial at Antietam September 7, 1862, when the wounded of the Army Corps from the Army of the Potomac were promptly removed from the field and cared for, being in marked contrast with the experience of the wounded of the other wing made up of troops from Pope's army. In the bloody battle of Fredericksburg, where, in addition to the great number of wounded, was added the confusion of a defeat, the ambulance companies nevertheless did their work with smoothness and dispatch, and the wounded were transported without confusion or delay to the division field hospitals. As reported by Surgeon Charles O'Leary, medical director of the Sixth Corps, it "afforded the most ploasing contrast to what we had hitherto seen during the war." This medical organization soon spread to the other armies of the United States, and was formally adopt- ed by Congress in the spring of 1864. It was not copied from European models, but, on the contrary, has been, in its essential features, adopted by all civilized nations, and it is probable that the name and fame of Jonathan Letterman are better known to-day to the military surgeons of Europe than in lii- 1 own country. Nor during his lifetime did this great and beneficent genius receive any promotion or any reward other than the commendation of his general and the admiration of his professional comrades. This splendid constructive work was done, and the vast responsibilities of chief medical officer of a great 576 REFERENCE HANDBOOK OF Till'. MEDICAL SCIENCES Army Medical Department Flo. 324. — Dr. Jonathan Letterman. army were me( and surmounted by a man who s ■riven only the rank and pay of a major. When the Surgeon-general proposed thai the medical directors of the armies under McClellan and Halleck be given the temporary rank of colonel, which was enjoyed by other staff officers, the War Department returned the ungracious and fatuous reply: "Refused unless ui be shown that the skill and efficiency of sur- is arc increased by an increase of rank and paj ." This rank was afterward given to the medical direc- of armies in the field by the Act of February 23, li is not surprising that Letterman, broken in health by his great labors ami disgusted at the blind ingratitude of those in authority, resigned from the service in De- cember, 1864, and died in San Francisco some years later. The Army General Hospital in San Fran- cisco, which receives the sick and wounded com- ing from the Philippine and the Hawaiian Islands, and which is the largest general hospital at present in the Army, has recently been named the Letterman General Hospital, in memory of this great organizer for whom it is hoped that some day the medical profession will demand official recognition which was denied him in his life- time, by the erection of a statue in Washington. The end of the Civil War found no less than 204 general hospitals containing 136,000 beds in opera- in the territory of the United States over an area extending from Maine to Florida, and westward be- yond the Mississippi. The Medical Department during the Civil War disbursed over 847,000,000, and id for 1,057,423 sick in its general hospitals alone, without counting those that passed through the field regimental hospitals. Of the medical staff, ll."> were shot in battle, of whom 42 died, and 2bo died of disease. This great struggle has left behind it as monuments of the labors of the medical profession, the Army Medical Museum and the great national institution known as the Library of the Surgeon-general's office. The record of their professional work is given in the "Medical and Surgical History of the Rebellion," which in spite of the advances in professional knowl- edge since that time, remains an inexhaustible mine of statistical information, while the reports of medical directors in the appendix are of permanent value and interest to all who are interested in the great and ever-recurrent problems of medico-military ad- ministration. The following remarks from an address made in 1879 on infectious diseases in the Army by the great German military surgeon Rudolph Virchow, show an appreciation of the accomplishments of the medical department of the Army during the Civil War far be- i what is common to members of the medical pro- fession of our own country: "It has been sharp necessity, this keenest of monitors, which has opened men's eyes through the heaviest visitations, so that they are compelled to notice what, to speak accurately, they would not see. Yes,, it is astonishing, what schools of suffering the armies have had to pass through before the truth line commonly acknowledged! Thus in the Cri- mean war, the French army lost one man out of every three, in their wholearmy, and it is calculated that of the 96,615 men who forfeited their lives, Vol. I.— 37 only Hi.Jlo fell before the enemy; about on equal number of wounded died in the hospitals. The re l, more than 7.~>.(H)(l men, f,-|| a sacrifice to dis- ea e. In the American civil War, 97,000 men died in battle, and 184,000 from epidemics and sickni What a huge ma "f pain and suffering, what a sea of blood and tears stands revealed in these figures I Hut, also, w hat a heap of fallacious regulat ions, of prejudices and misunderstandings. It is necessary to lav bare here the long list of these -ins ami mi-iakes; fortunately it is sufficiently well known in order to serve as a warning for others. But it must also be said that it was not necessity alone which exposed the evil and brought redress. That the French learned little or nothing in the Crimea, and the North Americans so much in their Civil War, that from that date onward begins a new era of military medicini — this depends not on the magnitude of the necessity which the Americans had to Undergo, which in truth was not greater than the French underwent in the Crimea. It was far more the critical, genuinely scientific spirit, the open mind, the sound and practical in- telligence, which in America penetrated step by step every department of army administration, and which under the wonderful cooperation of a whole nation reached the highest development that, relative to humane achievements, had hitherto been attained in a great war. Whoever takes up and looks into the comprehensive reports of the military medical staff will be again and again astonished at the richness of the experiences chronicled therein. The utmost accuracy of detail, painstaking statistics embracing the minutest particulars, an erudite exposition com- prehending every aspect of the practice of medicine, are here united in order to preserve and transmit to contemporaries, and to posterity, in the most thorough way possible, the wisdom purchased at so tremen- dous a price. The admirable medical organization of Letterman disappeared with the armies of Grant and Sherman, and Congress, weary of war, could not be induced to take interest in any military matter, except in the direction of reduction and economy. While all other nations made haste to apply 7 the lessons of our war and to remodel their medical organization in accor- dance with them, our own Medical Department reverted to ante-bellum conditions and went back- ward. The hospital stewards were the only perma- nent enlisted personnel, and all nursing and other work about the hospitals was done by an uninstrueted and constantly changing personnel of men detailed from the companies. No worse system could have been invented, and yet it lasted twenty-two years, until, in 1SS7, the first step toward a modern organization was made by the establishment of a hospital corps consisting of privates and two grades of noncommissioned officers. The medical officers then began the systematic train- ing of the personnel and the study of modern medical organization with a view to war conditions. This movement unfortunately was misunderstood by the officers of the line and met, especially at first, with much ridicule and covert opposition, the use of military titles by medical officers being especially resented. The outbreak of the Spanish War in 189S found the Medical Department with a personnel of 177 com- missioned officers and 750 enlisted men. This number was barely sufficient to perform the medical service of the regular army of 25,000 men in time of peace. When a volunteer army of 250,000 men was mobilized, and at the same time an expedition em- bracing practically the entire regular army was organized to attack Santiago, it was immediately evident that if the regular regiments were to be cared for by regular medical officers but few would be left to organize the medical service of the volunteer armies. Each of the volunteer regiments brought 577 Army Medical Department REFERENCE HANDBOOK OF THE MEDICAL SCIENCES with it into service three regimental surgeons and three hospital stewards, but no privates. The regi- mental and field hospitals had to be organized at the expense of this regimental medical personnel. The enlisted strength of the regular hospital corps was inadequate for "25,000 men, and as Congress failed to authorize the enlistment of volunteer Hospital Corps men, the situation in this respect became at once acute, and was only partially relieved by the clumsy expedient of authorizing the transfer of men from volunteer regiments to the regular Hospital Corps. We have seen how this emergency was relieved in great measure in the general and stationary hospitals by the employment of female trained nurses in large numbers. This assistance, of course, could not have been employed in the regimental and field hospitals. which marched with the troops and performed the service of removal of the sick and wounded from the front, but fortunately the short duration of the Spanish War made but small demand upon the activities of these mobile organizations. The volun- teer surgeons, though in many cases appointed with- out effective examinations, were, as a rule, capable and efficient physicians but were lacking in admin- istrative experience, and in practical knowledge of military hygiene. The troops were, in most cases, kept for long periods of time in their camps of mobili- zation and so the typhoid infection, which almost every regiment brought with it from its state camp, had good opportunities for dissemination. It was the accepted belief of military surgeons, as of the medical profession at large, in 1S9S, that the principal and almost the only method of dissemination of typhoid fever was by polluted water supplies, and the typhoid epidemic that swept through all the camps in the summer of 1S9S, regardless of the fact that for many of them the water supply was artesian, created consternation and surprise. The true conditions under which typhoid fever is spread as a camp disease were not understood until the publication, some years later, of the remarkable study of these epidemics made by Major Reed of the Medical Corps, and Majors Vaughan and Shakespeare of the Volunteer Medical i.e. which covered 20,738 cases of typhoid fever among 107,973 officers and men in ninety-two regiments. The military and sanitary lessons of this war were most instructive. They were studied with much and patience and every facility for arriving at the truth by a commission appointed by President McKinley to investigate the conduct of the War Department in the war with Spain, commonly known as the Dodge Commission, from the name of its chairman. Their conclusions were as regards the Medical Department: What is needed by the Medical Department in the future is: 1. A larger force of commissioned medical officers. 2. Authority to establish in time of war a proper volunteer hospital corps. 3. A reserve corps of selected trained women nurses, ready to serve when necessity shall arise, but, under ordinary circumstances, owing no duty to the War Department, except to report residence at determined intervals. 4. A year's supply for an army of at least four times the actual strength of all such medicines, hospital furniture, and stores as are not materially damaged by keeping, to be held constantly on hand in the medical supply depots. 5. The charge of transportation to such an extent ill secure prompt shipment and ready delivery of all medical supplies. G. The simplification of administrative "paper work," so that medical officers may be able to more thoroughly discharge their sanitary and strictly medical duties. 7. The securing of such legislation as will authorize all surgeons in medical charge of troops, hospitals transports, trains and independent commands to draw from the Subsistence Department funds for the purchase of such articles of diet as may be necessary to the proper treatment of soldiers too sick to use the army ration. This to take the place of all commuta- tion of rations of the sick now authorized. To these should have been added the creation of a corps of medical inspectors with adequate rank and powers. In the reorganization of the Army by the Act of February 2. 1901, no attention was "paid to the recommendations of this commission or to those of the surgeon-general, and the proportion of medical officers was not only not increased but was greatly reduced, while their prospect of promotion was taken away by disproportionate increase in the lower grades. The injurious effect of this legislation soon became apparent and it was found impossible to fill the vacancies created by the act or, without a lowering of the standard, to get more recruits for the medical corps than were sufficient to replace the annual 1. by death and retirement. Surgeon-general R. M. O'Reilly therefore, on December 24, 1903, placed in the hands of the Secretary of War, Elihu Root, a memo- randum in which the defects of organization of the act of February 2, 1901, were carefully and fully diseu- and a reorganization proposed which would earn,' out the recommendations of the Dodge Commission >u far as specific legislation was necessary to that end. The scheme proposed was finally enacted into law on April 23, 190S, and has resulted in the excellent organization of to-day. Meanwhile the Surgeon- general has kept constantly in view the recommenda- tions of the Dodge Commission so that all have been carried out with the exception of No. 2 — authority to establish in time of war a proper volunteer hospital corps. This has been for some years before Cong as part of a general law proposed by the War Depart- ment for the raising of volunteer armies, but remains without favorable action. Jeffeksox R. Kean. Army Medical Field Service. — Where any large number of men are to be employed in a given task, their organization into suitable groups is essential to the accomplishment of satisfactory results. \ machine must be created, each part of which works in harmony with the others and all are domina by a single will. No more complete and intricate machine exists than that found in a modern army, and that part of the mechanism relating to the functioning of the Medical Department is one of great and essential importance. This point has been too often overlooked; and the first years of our Civil War, with a sad experience which only lack of time and opportunity kept from being duplicated in the Spanish War, clearly demonstrated that zeal and patriotism cannot make up for defective organization and ab- sence of team work. It has been said that the best preparation for war is war itself. This is but a half truth. Ultimate good results may proceed quite as 578 KJEFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Field Service iiucli f'"«' -original ii ii^i akes recognized and sub- ie q U entJj ftwciided as from .successes achieved at the ,„,„,,( '\,>i- is training in the routine duties of ieaoe from its entirely different character, any eparation for Che new parts and changed cenery staged by war. We can. by studying in dvance the matter of medical Held service from the tandpoiat of theory, make our mistakes largely inder conditiaaiLS when knowledge is not, bought by Wood, suffering, and tears. It is easy enough : to care for wounded actually under his ands, bul I u problem in war is to bring the wounded irgeon, and the surgical supplies together i a suitable way and without undue interference with uiitary purposes. Not all these facilities can be rough! up I" the wounded under the limitations of ce the problem becomes largely one of vacuatiorj of the wounded from the zone of casualty i where fixed hospital establishments admit of ivision of every facility that ingenuity can .mil money can buy. The problem of medical irk, before being one of purely professional is thus first of all one of transportation of ats. ■neral way, there are three zones whose borders it overlap, and through which severely ounded will pass from front to rear, viz., collecting, ing, and distributing. Each has its specific •lief formations in which convalescing cases will be d and returned to the front. The whole is to pass the cripple back as quickly as pos- :i point where he will be out of the way, while ■turning the sound man without unnecessary delay i service with the colors. loses of the Medical- Department in War. — These EBcially l:nd down as follows: : The preservation of the strength of the )rces in the field (o) by the necessary sanitary res, (6) by the retention of effectives at the oat, and the movement of non-effectives to the rear obstructing military operations, and (c) by ie prompt succor and removal of wounded. Second: The care and treatment of the sick and in- ed :it the front, -on the lines of communications, ad in home territory. The primary purpose thus relates to military tonomics in the prevention of waste; only secondarly ■i ^derations of humanitarianism enter. The specific duties of the Medical Department in ar are included in the following: 1) The initiation of sanitary measures to insure ealth of troops. _ I The direction and execution of all measures of ublic health among the inhabitants of occupied ory. (3) The care of the sick and wounded on the march, in camp, on the battle-field, and after removal there- 1 1 ill The methodical disposition of the sick and wounded, so as to insure I lie retention of those effec- tive ami relieve the fight ing force of tin' aon-i ffecti re. The transportation of tin' sick and wounded. (Ii) The establishment of hospitals and other formations necessary for the care of the sick and in- jured. (7) The supply of sanitary material necessary for the health of the troops and for the care of the sick and injured. (8) The preparation and preservation of individual records of sickness and injury, in order that claims may l>e adjudicated with justice to the Government and the individual. The Sanitary Personnel. — A very large person- nel is necessary to carry on the work of the Medical Department in war. It is drawn from: (a) Medical officers of the regular army, 450 in number. Also from the officers of the Medical Reserve Corps, both on the active and inactive lists. The organized militia of the States, on mustering into tin' service of the United States, brings its own medical officers; while in the organization of any volunteer foi'res provision is made for the necessary attached sanitary personnel. (b) Physicians employed under contract, but not commissioned as officers. (c) Members of the Hospital Corps, as existing in the regular army and organized militia and as ex- panded to meet war conditions. (d) Members of the Army Nurse Corps (female). (e) Officers and soldiers of the line or staff detailed for duty with the Medical Department. (f) Civilians employed as clerks, drivers, laborers, scavengers, etc. ( noncommissioned officers, and seven privates take part at the aid station and keep in touch with the firing line. The equipment of the aid station is very simple, merely boxes of dressings, and light nourishment with facilities for preparation. This is an advantage, since it is no great task to establish or break up such a station, which may need to go into operation in more than one location during a tight. The first consideration is protection from fire, and usually the nearer the aid station is to the front, the safer it is from dropping projectiles. The aid given on the firing line will consist of the applica- tion of dressings, the stanching of hemorrhages, and the immobilization of fractures where practicable. It must be confessed, however, that the actual results accomplished on the firing line will probably be not great, and that sanitary assignments thereto are largely to encourage the soldier in a belief that, if hit, his injuries will be promptly attended to. With such encouragement lie will stand longer and fight, better. When troops are advancing by rushes across an open country, it is clear that to attempt san- itary work under such conditions is to invite useless destruction. The treatment at the aid station will usually be limited to first aid for wounded coming from the front who have not already received it; and to the readjust- ment of dressings, if necessary, of those who have. Fractures, if not previously immobilized, are here put in splints. Restoratives and analgesics are given as required. If practicable, stimulating food and drink are prepared. In general, as much as possible will be done here to reduce the burden of work which other- wise would subsequently fall on the dressing stations ami field hospitals, as well as relieve the sufferings of the injured. As a rule, no operations will be done here except such as are urgently needed to save life, as the ligation of an artery or performance of trache- otomy. It must be remembered that the further to the rear, the better the facilities provided and the greater the chances for successful surgical work. Prompt occlusion of wounds, in preventing infection, is the great thing. By great attention to this last point, the Japanese are said to have had a third of all their wounded back on the firing line within a month. The regimental surgeon must not permit his station to be overcrowded. All able to walk will be promptly started back to the next relief point in the sanitary chain which has in the meantime been established to the rear. Those unable to walk are turned over to the ambulance company bearers as soon as they arrive. The regimental surgeon therefore must make every effort to get into touch with the ambulance company, charging the wounded he is starting to the rear to report his location, or even detaching one of his sanitary personnel as messenger. Frequently a rough position sketch should be scut showing the location of the station and the best means of access to it. Darkness affords a convenient opportunity to evac- uate the aid stations and search the more advanced 581 Army Medical Field S.-rvii ■<■ REFERENCE HANDBOOK OF THE MFDtCAL SCIENCES positions. This work at night is very difficult and ar d , ' 1 ous. If his regiment moves, the surgeon closes his aid station and follows, never permitting himself to get out of touch with his organization. ( ttherwise an advance might leave an aid station so far behind thai it would not be able to fulfill its purpose. Any wounded thus left behind on moving the aid station would probably be taken over by an ambulance company, or some of the regimental sanitary personnel may be detached to remain with them. Similar action is taken in case of retreat. It appears from the foregoing that the first brunt of sanitary work is done on the firing line and at the aid station. The volume of casualties developing in a very short time will sometimes be tremendous, and sanitary assistance must be promptly rushed up from the rear. This is done by appeal of the regi- mental surgeons to their colonels, and by the latter to higher authority. Regiments have not rarely lost from one-half to two-thirds their strength in a single battle. Larger forces lose less in proportion; but a division may well lose a third, and in five great battles of the Civil War the winning side lost twenty per cent. or over. These losses do not fall equally on organiza- tions, but some are shot to pieces, while others in reserve may have lost scarcely a man. To meet the needs of such diversified casualty, the regimental sanitary service is not, by itself alone, sufficiently elastic, and further formations, about to be described, are necessarily brought into play. The Ambulance Company. — There are four am- bulance companies to a division. Like the field hospitals and reserve medical supplies, they are divisional troops, and subject only to the commands of the Division Commander and the Chief Surgeon. A Director of Ambulance Companies, with the rank ■of major, and with a sergeant and private of the Hospi- tal Corps as assistants, directly conducts ther manage- ment under the Chief Surgeon. The personnel of an ambulance company is as fol- lows: 5 medical officers, 1 captain and 4 first lieuten- ants; 9 noncommissioned officers, 2 sergeants, first class, and 7 sergeants; 1 acting cook; 69 privates, first class, and privates. In order to keep the organiza- tion as elastic as possible, for the reasons which appear elsewhere, specific assignments to duty are not made except in the personnel to accompany the wheel transportation, which is as follows: 1 lieutenant; 1 sergeant, first class; 1 sergeant; 1 acting cook; 2 musicians; 1 farrier; 1 saddler; 15 drivers. As to mounts, of the above company personnel the following are mounted: five officers, thirteen enlisted men. For transport of sick and wounded an ambulance company has twelve ambulances, each drawn by four mules. The official capacity of an ambu- lance is four recumbent and one sitting case; or two recumbent and five sitting cases; or nine sitting cases. For short distances, good roads and great emergency, these figures for sitting cases may be slightly exceeded. There are also four collapsible travois, one of which is carried on every third ambulance. These may be used with the pack mules, cavalry horses, or public or private mounts. Automobile ambulances will probably find a place in the military service. Each ambulance company carries twenty litters, beside which there are four on each ambulance. The latter, however, are needed as cots for the recumbent cases and are intended to be exchanged for loaded litters brought to the ambulance. For moving sup- plies, each company has three four-mule wagons. Two of these chiefly carry rations, forage, kitchen outfit, bedding rolls, officers' baggage, etc., and belong with the field train. The third wagon carries the equip- ment for the dressing station — a load of about 1,300 pounds. For use in country not practicable for wheel vehicles, or under exposure to fire, this dressing station equipment is loaded' on: fotnr pack mules which form part of the company transport. The supplies entering into the dressing statioi equipment are simple yet sufficient far their purpose They consist chiefly of an abundance of dressings an operating case, commode set,, detached servici medical chest, simple fo>tos, a couple of rolls ol blankets, a water filter., two tent flies, buckets basins, and lights for night work. The general function of ambulance companies is tt collect the sick and wounded of the mobile fo. ci transport thera to field hospitals. More specifically their_ duties in battle are to establish and operati dressing stations, help the regimental sanitary person- nel at the front, and collect audi remove the wounded by litters and ambulances, to the field hospitals They therefore bridge the entire gap between tht regimental sanitary service and the field hospitals. Generally speaking, an ambulance company ordereci into action proceeds about as follows: The company moves as a whole to th<> last point sheltered from fire. Here the wheel (transport i left behind under cover to await orders. Th* ninainder of the company, with its dressing station equipment carried on pack mules, moves to the vicinity designated for a station and locates in a protected spot, preferably near roads from front to rear, possessing a water supply aard, if possible, buildings. The latter are not only shelter, but convenient landmarks to which to> direct wounded. The company probably leaves her* about two medical officers and about nine enlisted men. This personnel at once establishes and prepares the dressing station to receive and care for patients. The remainder ol the company, consisting of, say, twenty litter squads, under two medical officers and five sergeants, moves forward either as a single detachment or several smaller groups to get into touch with the several regimental aid stations in the sector of the line they are ordered to handlo. As soon as they get into touch with these stations, they start the flow of wounded back to the dressing station, which is a variable distance — perhaps half a mile — further to the rear. As the wounded accumulate at this point faster than they can be cared for by the original dressing station personnel, the latter is reinforced from time to time from the litter bearer section. Ultimately, most of the latter may have been ab- sorbed into the dressing station and the work of collecting largely turned over to the regimental sani- tary service. The time when ambulance companies ought to go into action is decided by the chief surgeon on the number and location of wounded. They go in only when the local regimental personnel can no longer handle the situation. The same factors decide number and location of the stations to be openi d. As soon as the advance of troops or other factor has caused the enemy to so modify his field of fire as to enable the fairly safe approach of the wheel transport, it is sent for to come up to the dressing station. The dressing station is marked by Red Cross guidons and camp colors. If off the road, the way to it is indicated by these colors stuck in the ground as markers at convenient intervals. The dressing station itself is divided into the following depart- ments: Dispensary, kitchen, receiving and forwarding section, slightly 7 wounded section, seriously wounded section, and mortuary. Within ten or fifteen minutes after being ordered to establish, the stores should be unpacked and the kitchen in operation and ret to supply liquid nourishment. All wounded pass through the receiving section. Trivial injuries, after treatment, are sent back to their organizations with- out delay. Those disabled from fighting, but able to walk, may be sent to the station for slightly wounded, a field hospital or the advance base, as the Chief Surgeon may direct; they are usually organized into .".XL' ki:i i:i;i:\< i: handbook of Tin: mi.dk \i. SCIENCES Army Medical I leld ><n pounds; surgical dressings, 5,991 pounds; official blanks, etc., 492 pounds; instruments, 4o0 pounds Most of the articles carried are expendable. These articles are largely contained in standard size boxes with hinged lids. The wagons are packed under a definite scheme to tacilitate getting at their Contents. Three wagons are SO packed as each to cany practically a month's allowance of medicim . hospital stores, and dressing materials for one field hospital. The fourth wagon carries equipment; the fifth, baggage, tentage. and forage; and the sixth a general supply wagon largely carrying bedding. By having these reserve supplies available with the division, the deficiencies resulting from the expendi- tures depending upon action may be promptly re- moved and the sanitary organizations as well supplied in a few hours after action is over as they wen: before it began. Sanitary Tactics. — With comprehension of the num ber, size, and functions of the various mobile sanitary formations, as briefly outlined above, must come appreciation of the fact that their direction and management to good advantage is a task of great magnitude and much difficulty. The .Medical Depart- ment has a well defined system of tactics of its own, based upon and coordinating with general military tactics as a whole, under which its formations are handled, moved about, and administered to best advantage. To learn this properly is a study by itself, and one absolutely outside the sphere of education of the civil physician, who is largely help- less in such an administrative position. A mere professional training is only one of several necessary qualifications, among which a knowledge of the elements of strategy and military organization, pur- poses, and methods are paramount. In this sense, the term "Chief Surgeon is a misnomer, for he is an administrative officer rather than a professional attendant. The responsibilities of such an officer with troops in the field are tremendous; and after a severe action, with wounded by the thousands to handle under conditions which always partake of an emergency, they are greater than those of almost every other officer. He must be an organizer and executive of a higher degree of ability, so that the best possible provision to meet sanitary need may always be available at the right time, in the right place, and in the right way. Appreciating that a modern army is the most elaborate and complex human machine ever devised by man, he sees that the Medical Department functions as part of the general mechanism in a way best to promote the military welfare and to interfere least with the movements and disposition of troops. But to do this he must be informed of the plans of his commander and be able to apply this knowledge to suitable modifications in the management of the Medical Department. Under modern military organization, the infantry division, of almost 20,000 men, is regarded as the smallest tactical unit possessing the elements to cope with ordinary conditions and emergency. With such a force, the sanitary personnel at the front is very great, as already mentioned, and as adding to the difficulties of administering it, is very scattered. And the division is a small force for modern war. In any great battle, at least a dozen such divisions would probably make up one of the contending armies, and such a force would occupy a wide frontage. It is said that the Japanese had over 400,000 men before Mukden, with a battle line sixty miles in length. To control, direct, and smoothly operate the vast sanitary personnel required at the front, scattered as it must be and in each of its elements required to play a different but coordinating part under dissimilar environment and conditions, in the accomplishment of a single common purpose, is a task to which all but the best administrative capacity, fortified by special training, must prove unequal. Briefly, the great problem to be solved at the front with fighting troops is one of transportation and con- centration of the disabled. Conditions are utterly at variance with what they are in civil life. Through every problem runs the dominant requirement that 585 Army Medical Field Service REFERENCE HANDBOOK OF THE MEDICAL SCIENCES everything — humanitarianism included — shall yield to matters of military efficiency. Hence the army sur- geon must regard his military obligations required under his commission, as an officer, of greater effect than his Hippocratic oath as a physician; and to acquiesce, if need demands, in the subversion of the personal interests of the sick and wounded in the achievement by the nation of the common ultimate purpose of military success. The disposition of sanitary personnel and organiza- tions in marching columns is of material importance in respect to the provision of suitable sanitary assistance when and where needed, but with the reservation that the assistance thus made available shall be supplied with the least interference to military purposes and methods. The tactical formation of the column — particularly as to whether advance or rear guard formation — is always a controlling factor. There are no hard and fast rules as to the distribution of sanitary personnel, transport and supplies through the column, but there are certain general principles relating to these points, the observance of which will contribute greatly to having sufficient sanitary assistance available at the right time and place. In these principles, the factor of distance, or its equiva- lent in marching time, is basically important. To better appreciation of the matter, a little knowledge of the common dispositions of the combatant forces within the column is essential, and is given here as follows: For all practical purposes, we may consider that marches are to be classed as (a) route marches, in which troops are being moved from one place to another and under conditions in which encounter with an enemy is not to be considered; (b) marches with an advance guard formation, in which an enemy is being sought out and will be attacked or opposed; (c) marches with a rear guard formation, in which the column is retiring from a nearby enemy and is endeavoring to evade a general action. In route marching, the component units march in closed column, without any special intervals or dis- positions for offense or defense. In such case, the regimental and other sanitary detachments accom- pany the organizations to which they are assigned. Their exact disposition is a matter of no great im- portance, except that sufficient of the sanitary personnel must be assigned to the rear of each or- ganization to pick up and care for any exhausted or disabled therefrom. In practice, the great majority of the sanitary personnel would be aggregated at the rear for facility of control. TV'ith a detached battalion, all its sanitary personnel marches here. With the regiment, probably all except the regimental surgeon and his orderly, who rides with the colonel, and the surgeons of the two leading battalions, with their orderlies and one litter squad each, who march with their assigned organizations, follow the regimen- tal column. To each regimental organization is temporarily assigned for the march one ambulance with animals and driver. This outfit belongs to an ambulance company, is only loaned, usually for the day, and is temporarily under the jurisdiction of the regimental commander and surgeon. Its function is to pick up and carry on to camp such sick, ailing, and footsore as may require transportation. If not otherwise required, it may carry the belongings or even persons of exhausted soldiers; but its function is not to help supply transportation to a jaded army. Exhaustion in the military organization as a whole should be avoided by appropriate rests, or met by the later forwarding at a slower rate of speed, of detach- ments formed from individuals unable to keep up with the column. This ambulance on the march is practically a regimental hospital on wheels, discharg- ing its cases in the regimental area when camp is reached, to be there restored to duty, taken up in the regimental infirmary or transferred to a field hospital 586 as need requires. The medical officer marching ii rear of the regimental organization limits admissions to the ambulance to cases of actual necessity. If . company commander considers that one of his mei needs medical assistance or transportation, he writes a memorandum to this effect and gives it to a non commissioned officer; the latter, with the soldier falls out of column and waits by tin- roadside unti a medical officer comes up. The latter authorize; the admittance of the man to the ambulanci makes such other disposition of him as seems nec< sary, sending back to the company commander thi note, with the action taken by him in the case of thi soldier endorsed upon it. If more men have to fall out during the march than can be accommodate the single ambulance with the regiment, the excess i- directed to wait at some convenient point beside the road until the rear of the column as a whole arrives, bringing the intact ambulance trains with fun accommodations. This is the plan habitually employ- ed with troops in advance guard formation and march- ing to the attack. Any still greater excess of disabled could await the wagons of the field train, or those of the field hospitals, next to come up. Where a regi- ment is operating independently, it is assigned a total of three ambulances, which follow as a train at the rear of the regiment. In the column moving to the attack, special dis- positions of the sanitary personnel and transpo-t are necessary, variable with length of column and de- pendent upon the advance guard formation assumed. It is of the utmost importance, in controlling danger- ous hemorrhage and limiting the opportunities for wound infection, that sanitary assistance shall be available within a reasonable period after receipt of an injury. But this is generally practicable only for the tactical organized units, and the Medical De- partment gives no assurance that each and every injury will be reached and handled as promptly and effectively as might be desired. In its general pla small groups and individuals have of necessity to be disregarded, and the purpose is merely to endeavor to bring about the greatest good to the greatest muni Assuming an infantry regiment moving toward an enemy known to be in the vicinity in front, the gem procedure, somewhat variable with terrain, would be about as follows: (1) Six or eight mounted scouts, rapidly recon- noitering the roads ahead and on the flank, and about a mile ahead of the leading foot troops. (2) A "point," of an officer and four men, some 500 yards in advance of the next element. (3) "Flankers," variable as to number and interval, and radiating from the "point" out to 400 to 500 yards on each side of 1he road; thence parallel to it back to , the "support" of the advance guard. (41 "Advance party," probably one company, |i details as "point" and "flankers," and about 400 yards in advance of the next element of the column. No sanitary personnel will usually accompany the foregoing. If any are wounded, they must dress their hurts themselves with the first aid dressing carried on the person, and await the coming up of a formation large enough to warrant sanitary representation bcit g assigned to it. (5) "Support," probably of the remaining three companies of the battalion. This will march, say, 1,000 yards in advance of the "main body of the column." In the rear of the "support" will probably be found the battalion surgeon, his orderly, a noncommissioned officer, and two litter squads of the Hospital Corps. (6) "Main body," consisting of the two remaining battalions. Each battalion is accompanied by the sanitary quota just given above. The regimental surgeon and his orderly ride with regimental head- quarters, probably at the head of the "main body". (7) The remaining sanitary personnel, consisting REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ i in v Medical Field Service of the senior noncommissioned officer and four private Hospital Corps, with litters and park mule, forming the aid station party. m Regimental band, carrying company litters, officially placed under direction of the regimental .mi and under immediate direction of the senior sergeant firsl class, II. C, attached to the regiment, rhe three ambulances, closing in the column. ini [f the field train is present, it follows the buiances at a suitable interval, depending upon circumstances. If a regimental infirmary or regi- mental hospital is present, its transportation probably edes the field train. Communication is kept up between these different formations by individual soldiers marching at about 100 yards intervals and known as "connecting fil In this formation the regiment, excluding the nioiintril scouts, extends about one and one-half milrs from front to rear. Such an organization will march about three miles per hour, whence it appears that if a man in the "point" is wounded and the '■column" continues to advance, the surgeon with the support will reach him in about ten minutes, and the rear of the regimental column and ambulances in about thirty minute. In this formation, if the advance is checked, the 'point" is reinforced by the "advance party" and the latter in turn by the "support.'' The whole battalion previously forming the advance guard is now a unit on the firing line, and the battalion surgeon makes such distribution of his sanitary personnel as may be necessary. The other battalions successively arrive, and if necessary go into action. Each has a .sanitary personnel directly attached to it sufficient for its immediate needs. The field train is probably halted a couple of miles back. The ambulances are halted to await orders at the nearest point to the my which they could reach while protected from his fire. The aid station party, reinforced by the band, is continued on to a convenient point near the front, probably near the reserve, where it is held in readiness for movement to the proper place at the proper time. It will thus be seen that the military forces arrive in progressively stronger waves. The sanitary trees likewise accompany and immediately follow the latter. If opposition is slight, the column, in prosecuting the march, soon crosses the zone of casualty; if opposition is severe, the rear of the column mines up to the halted head and thus arrives within the zone of casualty. Either contingency is favorable to the work of the Medical Department. The wounded men will not have to march or be carried back to the surgeon, for the surgeon is himself normally moving up to him. The contingencies of tactics here naturally tend to bring the patient, the .surgeon, and the sanitary supplies together at the earliest possible moment. A rear guard formation is practically the same as the advance guard formation, except that the column is headed the other way. In other words, the situa- tion is the same as if all combatant individuals, detachments, and organizations had simply faced about. But for the sanitary personnel the above does not apply. In advance guard formation, reinforcements of combatant troops and sanitary a^-istanee are steadily moving toward the firing line ic front; but in rear guard formation the firing points are at the extreme rear, so that both combatant and sanitary troops steadily tend to leave the suc- cessive zones of casualty and widen the distance already ting between the wounded man and represen- tatives of the sanitary service. The purpose of the rear guard formation, moreover, is not to fight but to avoid fighting and to get away. The correlated factors of time and distance control the situation. Whatever is to be done for the wounded must be done quickly; and to be able to do it quickly sufficient assistance must !>'• available at tl i in I possible point in the column. Ami inasmuch a- wounded must be promptly removed if they an- not ' captured by the enemy, the need for plenty of wheel transportation as near as possible to the rear is obvi- ous. Probably half the SS i innel and half the band will thus be assigned to the rear guard, at hast two litter squads with t he rear party. One or re ambulances would immediately precede the "support" of the rear guard, falling out on ignal and halting until reached by litter parlies bringing up injured men from the rear. Theaid station party, for which there '.'.ill be little use unless tin- "com- mand" is forced to turn and fight, precedes the main body. Any hospital supplies arc with the held train a variable interval in advance of the main body. The same principles as illustrated lor the regiment apply to larger and smaller forces. In such ins t a Qi ■ . the proportionate strength and composition of per- sonnel, and intervals between formation-, vary. The location and strength of sanitary personnel likewise varies. With larger forces than the regiment, ambu- lance companies, field hospitals, and the reserve sani- tary supplies have to enter into our calculations in connection with marching troops. With a brigade in advance guard formation, an at tached ambulance company ami field hospital would march at the rear of the column. As a brigade in such formation marches about its own length in an hour, it is clear that all sanitary assistance available can be up in about an hour after the head of the column is fired upon, and by this time a general action has been begun. This time is not excessive for the regimental detachments to handle the situation by themselves. In rear guard formation the field hospital would precede the "main body", together with filled ambu- lances, while empty ambulances and the ambulance company personnel would precede the rear guard, ready to turn and assist the sanitary personnel of the latter if need requires. But the infantry division is the tactical unit. It would normally have a brigade of infantry, with some artillery, in its advance or rear guard. Its advance guard is 6,000 yards long and separated by some 2,000 yards interval from its main body. The latter is 10,000 yards long, total 18,000 yards. The trains are about 10,500 yards, or a total of say 29,000 yards. But such a column cannot be kept closed up and will elongate on moving by ten per cent, and probably more. The fighting column will thus be 20,000 yards from front to rear — or say about eleven miles long. The trains will follow the column at a variable interval, say three to five miles. From a tactical standpoint, it is important that nothing which can be spared should have a place in this column and thus interfere with the deployment of the maximum number of men in the minimum time. But humanitarian reasons and the need for getting wounded attended to reasonably promptly, by reason of its psychological effect on the uninjured, combine to require that some provision for the care of wounded be made. The disposition will be about as follows: one ambulance company, less all its wheel transportation, or with dressing station wagon merely, will follow the advance guard. This position is about 6,000 yards from the extreme ftont, or about an hour's march. About the time that the advance guard deploys and gets heavily engaged, this leading ambulance company will have come up and be on hand to assist in caring for casualties. No ambulances are sent with the advance guard, as these would occupy valuable road space and merely be in the way. Until the main body is out of the road, the latter is blocked for removal of wounded. The three remaining ambulance companies, complete, and the train of the one sent with the advance guard, follow at the rear of the main body. They are thus some eleven miles from the front, where they could probably arrive in about four and one-half hours as a 587 Army Medical Field Service REFERENCE HANDBOOK OF THE MEDICAL SCIENCES division can move only relatively slowly; or three and one-half hours after the first ambulance company arrived on the scene, and shortly after deployment was completed and the action become general. The field hospitals, heading the trains whenever battle is imminent, would pull on to within half a dozen miles of the action, and be halted at a convenient place to await orders. If need demanded, the field hospitals could reach the field one or two hours after the ambulance companies, dependent on the length of the interval between the rear of the column and the trains. The reserve medical supplies usually bring up the rear of the supply train. They are about six miles from the field hospitals at the head of the train, and could thus arrive on the battlefield about two and one-half hours later if the sanitary material were needed. It thus appears that as the casualty situa- tion on the field develops, a succession of organized sanitary relief units comes up and thus are sent into action according to the needs of the situation. The actual positions of the foregoing formations with the division after battle is on is wholly variable with local conditions and terrain. It could, in the nature of things, practically never be twice alike; but perhaps some such disposition as follows would fairly express the situation: In the First Brigade, the First and Second Infantry have each the First and Second Battalions on the line and the Third Battalion under cover within a hundred yards or so in support. The Third Infantry forms the brigade reserve, and is perhaps several hundred yards in the rear of the other regiments. This brigade has a frontage of, say, two-thirds of a mile. The Second Brigade is, say, immediately on the right of the first. Its interior disposition is approximately the same as with the First Brigade. The Third Brigade is the divisional reserve, and is under cover, say, half a mile to the rear and at a central point whence any part of either the First or Second Brigade can be quickly reinforced. Under such conditions, the points of medical relief in operation might be about as follows: With the First and Second Battalions of the First and Second Infantry, sanitary aid on the firing line as expressed by the presence of a surgeon, orderly, non- commissioned officer and one or more privates. Somewhere back of the First and Second Battalions, as near them as possible but probably near the reserve battalion, would be the aid stations of the First and Second Infantry. The sanitary personnel of each of these is that of the aid station party, plus much of the sanitary personnel of the nearby reserve battalion, plus the band. Wounded from the two battalions of each regiment at the front drain into each of these aid stations. Several miies to the rear, preferably on a side road not utilized by the dressing stations and field hospital, is the station for slightly wounded. The battalion and regimental surgeons are directing the slight cases to start there at once. Back of the two regiments on the firing line of the First Brigade, preferably at a point near the center draining both flanks, is located the dressing station. This brings it somewhere near — though probably in the rear of — the brigade reserve. Wounded from the two regiments engaged and their aid station; converge here. Only very exceptionally would sanitary assistance be drawn from the regiment in reserve, which may at any time have to go into action. The Third Brigade, in reserve, is for the time beipg inactive. If successful, it will be pushed against the enemy; if unsuccessful, it will form the rear guard to hold off the enemy and permit of an orderly retreat. It is not suffering casualty and has no sanitary forma- tions in operation. It may not be needed for some hours. Some of its sanitary personnel may be tem- porarily detailed by the Chief Surgeon to assist at the dressing station nearby. The dressing stations of the First and Second Bri- 588 gades are evacuating their wounded by ambulance on a field hospital just established some three miles back at a point readily accessible from both the First and Second Brigades. Perhaps near this point are the two reserve ambu- lance companies, and three field hospitals, packed up and awaiting orders. A transport column has just arrived here from the rear, and will load its ambulances at the field hospital as soon as the cases are in readiness to be evacuated farther to the rear. Back some five miles on the route over which the division advanced, halted with the trains, are the wagons of the reserve medical supply. Eight or ten miles away is a rest station, where the transport column will halt to rest en route on its return with wounded from the field hospital. Fifteen or twenty miles away is an evacuation hos- pital, located at railhead and serving as a receiving and forwarding hospital for the sanitary train service leading to the base. Nearby is another evacuation hospital, packed in wagons and in readiness to be pushed to the front when and where needed. An advance medical supply depot has been established at railhead. In the foregoing scheme, the sanitary service with the cavalry, artillery, and other troops is not con- sidered, as the infantry furnishes all but a small per cent, of the total losses. In the rear of the field hospital above mentioned, the sanitary formations relate to the line of com- munications, or zone of evacuation, next to be con- sidered. II. The Evacuation Zone. — Prolonging the col- lecting zone to the rear comes the evacuation zone. This includes the line of communications, the great channel through which the military force at the front is sustained and at the same time relieved of it- human debris. The sanitary formations for the divi- sion in this zone are as follows: transport column; evacuation hospitals; medical supply depots; hospital trains and boats; base hospitals; base medical supply depots. All these formations come under the direc- tion of the Chief Surgeon, Line of Communications. They are depended upon to take over the wounded from the division at the front without unnecessary delay, and thereby free the military force at the front from an encumbrance which would otherwise largely paralyze its fighting efficiency. The various for- mations in the zone of evacuation may briefly be discussed as follows: The Transport Column.-. — One such organization is allowed each division. Its primary function is the evacuation of field hospitals, and transportation and care of patients therefrom to evacuation, base or other hospitals on the line of communications; or to points with train or boat connection by rail or water to such hospitals. The transport column has 4 medical officers, 1 major, commanding, assisted by 3 junior medical officers; 4 sergeants, first class; 16 sergeants or cor- porals; 4 acting cooks; 16 drivers; 4 orderlies; and 40 litter bearers. Its transportation consists of 1*2 ambulances and 3 wagons. The supplies are identical with those furnished an ambulance com- pany, except that no pack mules or dressing station equipment are supplied. This organization is weak, and capable of meeting ordinary conditions only. However, its work partakes much less of emerge: than does that of ambulance companies: and tin' time factor for removal of the disabled, while al v. important, is here less frequently paramount. On the march, transport columns or sections thereof keep in touch with the column and are brought up to take over patients collected by field hospitals, which must again be freed. These disabled are removed to the designated point, and the transport column REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Field Service promptly returns toward the front. Ordinarily ii will not work in the rear of evacuation hospitals. Whin battle is imminent, the transport column is usually heavily reinforced by both vehicles and bearers. Empty army wagons and hired or iin- -,.,1 civilian trams, automobiles, etc., are em- ed, Mini extra sanitary personnel sent up from the casual camp at the base. Just before battle, all the e resources should be moved as far to the front as ticable, so as to be promptly available. As soon sufficient patients requiring return to the rear imulate at one or more lield hospitals, the trans- port column will receive, provide fur, and transfer them to the rear. It also provides for the slightly wounded, able to walk, who may have been directed Rest Station. — When the distance to be travelled by the column is more than a half day's march, or the lition of the patients require it, the transport Mia establishes rest stations at convenient points. Hours consumed in travel, rather than distance actu- ally traversed, largely determine location. These stations may correspond with quartermaster's supply depots; they certainly will with one of the etapes established along the line of communications. Rest stations are formations having no definite ■ unci or equipment. They can usually be established in houses and can be materially outfitted local resources. They are intended only for temporary treatment and care of patients until they can be moved further. Ordinarily the duties of the- personnel at these stations are limited to the readjustment of dressings and the supply of food and s'n.'lirr to patients. Emergency operations may, however, be done when necessary. Tlic personnel for rest stations may very legiti- ely be drawn from the Red Cross, who can perform the necessary work to excellent advantage. Some- times rest stations may be kept up for considerable periods with the same personnel, or they ma)- be iporarily created for the needs of a single stop or night. When patients must be left behind at I stations, sufficient personnel and supplies are left with them, and the Chief Surgeon of the Line of Communications is duly notified. The general re- lations and functions of transport companies are analogous to those of ambulance companies. Evacuation Hospitals. — Two of these hospitals are mobilized with each division. Each has an official capacity of 324 patients, or a total of 624. Under stress of emergency they may be expanded to accom- modate many more than that, since the nature of their service will frequently cause their establishment in communities where buildings are available and supplies and personnel may be materially supple- mented from local resources. The personnel of an evacuation hospital is as follows: Fourteen medical officers, divided into 1 lieutenant colonel in command, and of the juniors, I executive officer, 1 quartermaster and commissary, 1 operating surgeon, 2 assistant operating surgeons, 8 ward surgeons; 8 sergeants, first class, of whom 1 is general supervision, 1 in charge of office, 1 in charge of quartermaster and commissary supplies and records, 1 in charge of kitchen and mess, 1 in charge of detachment and detachment accounts, 1 in charge of patients' clothing and effects, 1 in charge of prop- erty and records, 1 in charge of dispensary; 16 ser- geants, of whom 1 is in dispensary, 2 in store rooms, 1 in mess and kitchen, 4 in office, 2 in charge of police, 5 ward masters, 1 in operating room; 10 acting cooks; 119 privates first class and privates, of whom 76 are ward attendants, 1 in dispensary, 3 in operating room, 10 in kitchen and mess, 4 in store rooms, 5 with transportation, 4 orderlies, 4 in office, and 12 on outside police. The evacuation hospital has little transportation. There are two four-mule wagons for ordinary hauling, and three ambulances for the movement of the dis- abled. The latin' is sufficient, as although the num- ber of patients to i»- moved is large, the distano are short and the time factor is rarely of importance Evacuation to the rear of tin- evacuation hospital will very frequently in- bj rail. The equipment of an evacuation hospital is prac- tically that of three lield hospitals — into which it can be broken up— pin- a considerable amount of heavy material, such as folding field furniture, etc., not car- ried by lield hospital-. It is fully provided with tentage for shelter. It weighs, packed, about 66,000 pounds, and thus requires about thirty wagon to move it. These wagons are to be supplied by the Quartermaster's Department as need requires. The institution is a fairly mobile one, but it does not ordinarily need to move often, suddenly, or to very great distances. The evacuation hospitals form a central point toward which the collecting zone converges, and from which tile stream of disabled Hows toward the rear to diverge later into appropriate relief establishments. The primary function of the evacuation hospital is to replace held liospilals so 'hat the latter may move with their divisions, or to take over their sick with the same end in view. Secondarily, it is used for ordinary hospital purposes on the line of communica- tions. One of those with the division is usually established at railhead as a receiving and forwarding hospital, while the other is, if necessary, pushed out a day's journey or shorter distance nearer the front. Sometimes an evacuation hospital may be set aside, in whole or part, for the treatment of infectious diseases. The military situation controls the location of evacuation hospitals, but they should, when pos- sible, be located on a railroad or navigable stream. The vicinity of a town or hamlet is very desirable; but access by good roads, good water, and plenty of fuel are essentials. If suitable buildings are available, the evacuation hospital is habitually established in them, and little or no tentage is pitched. Many such buildings, as hotels, are already supplied with every- thing for the comfort of patients except medical supplies; other buildings, as warehouses, schools, halls, etc., may be readily converted to hospital use by the supplies and equipment carried. When a battle is expected, the evacuation hospitals are cleared, packed, and brought forward to a point convenient to the scene of expected action. As they are cumbrous and can only move relatively slowly, they are not attached to troops, whose movements they would hamper. They are held in readiness somewhere conveniently on the line of communica- tions, so as to open on the spot or move further forward as the Chief Surgeon of the Line of Communi- cations may direct. Once established, evacuation hospitals are not ordinarily moved during combat unless the troops have advanced so far that the distance makes it easier to move the institution to the patients than the patients to the institution; or when the natural route of evacuation of wounded no longer passes through them; or when the field hospitals are so overwhelmed with wounded that it is necessary to supplement them without delay. After a battle, the evacuation hospital may move up to or near the field and take over the wounded from the field hospitals, or take over the latter, equipment and all, supplying similar equipment from one of its sections for a new field hospital which, with the field hospital personnel thus released, goes forward to rejoin the division. The duties of an evacuation hospital are much like those of a field hospital, except that it is not so governed by emergency and is intended to afford a longer and better opportunity for treatment than field hospitals can give. In a general way, the organization of the evacuation hospital into depart- ments corresponds with those already outlined for field hospitals. 589 Army Medical Field Service REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The character of surgical treatment given wounded in evacuation hospitals will naturally vary with con- ditions. When during or after battle very many wounded are coming in, the treatment which can be given will not be much more extensive than that afforded in field hospitals, viz., emergency operations and those intended to fit the patient for further transport. But when few wounded are coming in and an early move is not probable, complete treat- ment is usually given. Excellent facilities for surgical asepsis are almost always available. Like all other medical formations, the evacuation hospital is in- tended to facilitate the further transport to the rear of serious cases liable to be permanently incapacitated, or those calling for more protracted treatment than the nature of such establishment is intended to pro- vide; while on the other hand it is intended to re- tain all cases offering prospect of early recovery and return them to duty with their organizations at the front. Every effort is taken here, as elsewhere, that wounded soldiers shall not separate themselves from their commands further than is absolutely necessary. To facilitate administration, two or more evacuation hospitals establishing in the same town or vicinity may be combined under one head; or the whole or part of the personnel of one such hospital which is not itself established may be sent to reinforce that of another. Such matters, together with the opening or closing of these hospitals, with when, where, and how their patients shall be evacuated, are decided by the Chief Surgeon of the Line of Communications. Upon him devolves the responsibility of freeing the forma- tions at the front of wounded, and keeping the movement of the latter back to the rear uninterrupted so that congestion at any point or points may be avoided. Particularly is it necessary that the non- effectives shall be promptly removed from the zone of operations. An appropriate field of usefulness of the Red Cross is in taking over one or more wards of an evacuation hospital, or in performing such other duties in connection with it as the medical officer in command may deem fit. Base Hospitals. — These are sanitary formations of the line of communications. One is mobilized for each division, and has an official capacity of 500 beds. It is capable of caring for more than that number of disabled under stress of emergency; and probably, as was the case in the Civil War, many would be greatly expanded. The personnel of a base hospital includes 20 medical officers, of whom 1 is a lieutenant colonel in command; 1 major, as operating surgeon; 18 junior medical officers divided into 1 executive officer, 1 quarter- master and commissary, 1 pathologist, 1 eye, ear, nose and throat specialist, 2 assistant operating surgeons, 12 ward surgeons. There is also 1 dental surgeon. There are 8 sergeants, first class, of whom 1 is in general supervision, 1 is in charge of office, 1 in charge of quartermaster and commissary supplies and records, 1 in charge of kitchen and mess, 1 in charge of detachment and detachment accounts, 1 in charge of patients' clothing and effects, 1 in charge of medical property and records, and 1 in charge of dispensary. There are 16 sergeants, of whom 1 is in the dispensary, 2 in storerooms, 1 in mess and kitchen, 4 in office, 2 in charge of police, and 6 are wardmasters. There are 14 acting cooks; and 1 1 ~> privates, first class or privates, of whom 68 are ward attendants, 1 in dispensary, 2 in operating room, 1 in laboratory, 14 in kitchen and mess, 12 outside police, 1 dental surgeon's assistant. Also 46 female nurses. The medical supplies, furniture, and equipment of a base hospital weigh 92,000 pounds. It might some- times be established under canvas, and for such con- ditions 121 hospital tents are authorized as shelter. But ordinarily it will occupy buildings taken over for the purpose, or erected in the form of frame pavilions especially adapted to hospital purposes and 590 built according to the official specifications filed in the office of the Surgeon General. The base hospital is provided with 3 ambulances and 2 four-mule wagons for ordinary hauling. Any additional transportation required is secured as needed from the Quarter- master's Department. The base hospital is rarely if ever moved in wagons, but is habitually brought up by boat or rail to the point of establishment at the base from which the military movement is launched. Its equipment is very complete, and nothing in the way of supplies or personnel is lacking to facilitate the recovery of patients. As troops advance further from their main base, railroads are repaired and one or more suitable points become advanced bases. New base hospitals are established at these points, since those already estab- lished further back are very likely now too far sepa- rated from the advancing force. The ones first established still continue their functions, but as the line of communications lengthens, new ones are established to form links in the sanitary chain at suitable intervals more convenient for the handling of sick and wounded. Where battle by a large force is expected, several base hospitals may be opened and held empty in readiness to receive the wounded who may be expected — or the personnel of those al- ready in operation may be augmented by that of those not yet established Base hospitals are intended to receive cases from the field and from evacuation hospitals, as well as cases originating on the line of communications and the base. Being completely equipped from a medical standpoint, it is intended that they shall give com- plete treatment to the great majority of cases sent to them, forwarding to home territory only such cases as require special treatment, are not likely to be fit for service for a considerable period, or will probably be permanently incapacitated for further duty. But where their capacity is being exceeded, or where heavy fighting is in immediate prospect, they will either have to be evacuated of suitable cases or rein- forced by the opening of new hospitals or the expan- sion of accommodations already existing. These hospitals send out the necessary personnel to meet sick arriving from other hospitals or from the trans- port columns, but such receiving parties will ordinarily not go further than the adjacent railroad station or points of debarkation. When evacuating cases further to the rear from advanced base hospitals, the necessary personnel and supplies are drawn from the latter. Several base hospitals in the same vicinity may be combined under a single head. As frequently happened in the Civil War, they may be converted into general hospitals. In a general way, the internal management of base hospitals conforms to that of general hospitals. No man capable of further duty in the immediate future should ever be sent further to the rear than the base hospital, for experience amply shows that the services of a great proportion of the cases getting further to the rear will probably be lost for the campaign if not for the war. While it is necessary for the surgeon at every field establish- ment of the Medical Department to exercise great discretion as to who shall go further back, who shall be retained, and who shall be returned to the front, this perhaps applies with greater force to the base hospital. It is most important that those formations shall not become clogged; for if this occurs the more mobile organizations near the front, having no place into which they can discharge their patients, must inevitably become congested and immobilized. Convalescent Camps. — When necessary, the chief surgeon of the line of communications may establish a convalescent camp or camps at the base, or in the vicinity of base hospitals established along the line. Such camps are branches of the base hospital near which they are situated. The purpose of the convalescent camp is to relieve REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Field Service -Mire in the base hospital by permitting the therefrom of all such cases as are well on ecov'i ry, and which rest and time rather than edical care are needed for a cure. It frees many beds which would otherwise be occupied, nl holds under control and for further service any who, if evacuated further to the rear, would be radically lost to the army. Held here under • oversight, th?y can be forwarded to their ions at the front as their condition and iportunity warrants. These convalescent camps, practically emergency formations, have no i or organization. In the Civil War, thej metimes grew to such vast size as to be difficult of lininistration and management. One being now d to a division, it is probable that a size equal base hospital which it relieves of a certain patients will not be exceeded. Uniting es, closed but healing flesh wounds, cachexias, lility following any cause furnish legitimate i such camps. No personnel can be specified advance for these camps, as it naturally depends' pon the number and character of cases present in ii latter. The same remarks apply to the equip- Facilities for shelter, nourishment, sleeping ausement are about all that are required. arge buildings with grounds, located on the outside towns. ina\ be taken over; or frame partition uildings may lie specially constructed for the pur- ose on attractive sites. Tentage would rarely be sed except for temporary emergency. Super- v medical officers could be assigned in charge, ith a necessary sanitary personnel detailed from ial camp. Disease Hospital. — One such hospital iv he established for each division as need demands, personnel, or equipment is prescribed, as arily vary with the number and nature f the cases to be eared for. All large bodies of ■oops not infrequently present cases of dangerous issible infections, which must be isolated as on as possible. The contagious disease hospital is branch of the base hospital whose need- it serves, cing located conveniently thereto yet far enough .ay to secure the necessary isolation. The person- el is assigned by the chief surgeon of the line of immunications, . who makes the necessary drafts lereto from the casual camp. The nature of the luipment varies, but corresponds in a general way ) that of the base hospitals. It would usually be cured direct from the base medical supply depot. he use of buildings is preferable, and conditions are -ually such that these can be obtained. If a large umber of contagious eases have to be treated, the i.i.f surgeon of a field arm}' may set aside an evacua- ion hospital for special service as a contagious isease hospital. Small hospitals for contagious .ay need to be established along the line, so hat these cases need not be moved. ial Camps. — These camps are designated for eption, shelter, and control of the unattached anitary personnel on their arrival and during their tay at the base of operations. They are established >y the Chief Surgeon of the Line of Communications, nd are under the immediate command of the senior I officer on duty therein. These camps are I iblished in the proportion of one to each division, hough several may be merged when several divisions re operating together as a field arm}-. Sanitary ecruits, Hospital Corps men discharged from hospital >r returning from furlough, absentees from any cause, md special detachments returning from the front 'port here, and are taken up under a company irganization. From this, drafts are made on request if the Chief Surgeon of the Division to replenish anitary organizations at the front weakened by leath, sickness, discharge or other causes. From it, he organizations on the line of communications are manned, and the necessary personnel for any spei ial put pose is draw n. Iia*' U. ■ ['he 1 t he point from which a military force draws it- supplie . a sufficient quantity of which is rapidly accumulated to meet pn ,ni and probable needs, lii making this provision for material, the Medical Department has its part to play, and establishes a supply depot thereat for the purpose. The personnel prescribed for this formation is 2 medical officers, 1 sergeant, first class, - sergeants, and 12 privates. The amount and character of supplies to be carried in stock by the base medical supply depot is fixed by > : ieneral. However, they must be ample to constantly meet all requirements of the sanitary sen ice at the front , on the line of communica- tions, and at the base. Some elasticity is necessary according to the needs at the front, the operations in prospect, facilities for transportation, etc. Among other items, a large number of iron frames as litter supports, lor use in fitting up baggage cars for the conveyance of wounded, are carried in stock. As the troops advance and the line of communications lengthens to a degree where it is difficult to make issue of supplies to the divisional sanitary units, one or more branches, or advance medical supply depots, may be pushed to the front. One is usually if not invariably established at railhead. Issues are made from these depots to organizations along the line of communications. Ordinarily, only the divisional -anitary units will receive supplies direct from the base medical supply depot. Regiments will replenish their stock from a designated field hospital or the reserve medical supply. The base medical supply depot is habitually established in a building. Its difficulties are many, for its efficiency largely- depends upon facility of the transportation of supplies called for, and transportation is in the hands of another department. Hospital Trains. — There are two kinds, regular and improvised. The regular trains are made up of ten cars each, of which eight are for patients. The official capacity is 200 patients. The personnel of such a train is made up of 3 medical officers; 1 sergeant, first class; 2 sergeants; 2 acting cooks; 2 orderlies; 20 privates as nurses. The equipment varies with the special needs of the situation. In time of emergency, improvised trains for patients are made up of any available cars and turned over to the use of the Medical Department. Troop trains moving up to railhead may have their empty coaches filled with less severely wounded on the return trip. Empty baggage or freight cars, made more or less comfortable with litters, straw or hay, may carry back recumbent wounded. On many occasions it is probable that wounded, as in the Russo-Japanese War and our Civil War, will be sent back in these trains without any special preparation of the latter, as a result of unfavorable military conditions. In ordinary freight or baggage cars, all patients carried for any distance must be regarded as recumbent, and the capacity based on twenty-five patients per car. Special litter fittings for the conversion of box cars for hospital purposes are supplied by the Medical Department. They are so assembled as to provide recumbent transportation for twenty-four patients per car. They are kept in stock, knocked down, in the base medical supply depot, and are sent forward so as to be at railhead on the eve of impending battle. The personnel of improvised trains depends on the needs of the situation. It comes either from the casual camp, or the large hospitals at the base or on the line of communications. Supplies would usually come from the base medical supply depot. Hospital trains and improvised trains for patients may operate in hostile territory, in home territory, or both, according to tactical and geographical con- siderations. Abroad they are directed by the Chief .391 Army Medical Field Service REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Surgeon of the Line of Communications; in home terri- tory, by the Surgeon-General. Medical officers com- mand these trains. In transporting patients, they are particularly charged to give due warning to the institution to receive them of the time of arrival and number of disabled. The schedule of train service is arranged by the Chief Surgeon of the Line of Com- munications. Hospital Slu'ps. — These can only relatively rarely be used on the line of communications. However, in the Civil War they rendered invaluable and tremendous service, particularly on the Mississippi and its tributaries. Where navigable streams are available, they will usually offer better opportunities for the more comfortable and expeditious evacuation of the disabled than can be had by land, and the necessary boat service should be at once organized, the personnel and supplies coming from the sanitary service of the line of communications. But in over-sea expeditions, hospital ships and ships for patients are required; and both are provided by the War Department. The former are of a permanent and elaborate nature, while the latter are usually transports fitted up in emergency for the return trip to bring back the less severe class of the disabled. The former are outfitted at home, and the latter from the main base in foreign territory. All these ships are under the command of the medical officers in charge, who have exclusive direction of all but the technical handling of the ship, which latter remains vested in the sailing master. The capacity, personnel, and supplies of ships for patients naturally varies with availability and requirements. Perhaps about one-third of its troop capacity may be regarded as a fair average of the capacity of a return- ing transport to carry patients of the less severe class. Regular hospital ships are intended to have a capacity of 200 beds, and to carry the more severe cases. As a matter of fact, since our Government owns no army hospital ships in time of peace, the capacity of those in war will vary with the facilities afforded by the most available ships of the merchant marine, remodelled for the purpose. In the Spanish War, our regular hospital ships were the "Relief," " .Missouri," and "Bay State, "all utterly dissimilar as to size, tonnage, and construction. The personnel of the official hospital ship is 1 major and 4 junior medical officers; 1 sergeant, first class; 4 sergeants; 5 acting cooks; 30 privates. The equipment of these hospital ships is most elaborate and complete, nothing being lacking which could in any way contribute to the comfort and welfare of the patients. III. The Zone of Dispersion. — While this article is supposed to deal only with army medical field service, it is impossible to conclude the discussion without further consideration than that of the zone in which the patients fall and are collected, and the zone through which they are removed. Many of the dis- abled pass into a third zone, or zone of dispersion. In this latter zone they will be scattered, for conven- ience and availability of treatment and care, through various general hospitals and the convalescent camps attached thereto. All of these are in home territory. We now have two such army hospitals receiving and caring for all kinds of cases, one in San Francisco and one in Washington, D. C. Both are capable of great expansion. In addition, as many other such inst itutions as may be needed in any future war would be established at strategic points, and of a size to meet necessary requirements. Plans and specifications for such hospitals, drawn up on the pavilion system, are already prepared in the office of the Surgeon- General, and they may be erected out of lumber and ordinary building materials with great rapidity. During the Civil War, the Northern forces had at one time 192 general hospitals, with 118,000 beds. Some such hospitals accommodated 3,500 patients each, but it is not now believed to be good policy to have them of more than 1,000 bed capacity. These general hospitals are under the exclusive control of the Surgeon-General, and are set outside the juris- diction of department commanders. The equip- ment of the general hospital is varied and elaborate, approximating, except in the relatively temporary nature of the buildings, that of high class civil hospitals. The personnel is very complete, and in these general hospitals will be found the best expert medical as- sistance found in civil life, drawn temporarily to the colors through motives of patriotism. Receiving hospitals may be established at posts habitually utilized for the discharge of troop trans- ports. They may be branches of neighboring general hospitals; or they may themselves be ad- ministered as general hospitals. In time of great stress, or when official hospital accommodations are insufficient, contracts may be made with civil hospitals conveniently located," and patients sent there for necessary treatment. Usually such cases are supervised by a medical officer, to maintain some military control and see that the necessary records are properly kept up. The system is undesirable, as tending to absenteeism and will probably not now be employed any more than ab- solutely necessary, though freely used in the Civil and Spanish Wars. In the past, many disabled have been furloughed to their homes as soon as able to travel, where they have received private medical attention subsequently paid for by the Government. This system is highly undesirable, as letting the patient escape absolutely from military control, and will probably not be greatly employed in the future. Hospitals for prisoners of war are established by the Surgeon-General at points designated by the Secretary of War. They have the status of general hospitals and are managed directly under the Sur- geon-General, except that the officer charged with the custody of the prisoners will maintain such guards over the hospital as are necessary to prevent libera- tion or escape of prisoners under treatment therein. A total necessary bed capacity for the entire force, front to rear, is fixed at the equal of ten per cent, of the total borne on the muster rolls. This number does not include the accommodations of the field hospitals, rightly considered as being unavailable except for brief emergency treatment. Edward L. Munson. Army Medical Statistics. — Broadly speaking, the main causes affecting the health of troops are the manner of living, the environment, and the fond supplied. The first relates to the occurrence of overcrowding, imperfect ventilation, want of clean- liness, and inattention to personal hygiene. The second is typified in the accidents arising from atmos- pheric or telluric influences, such as rapid death from heat and cold, the comparatively transient influei s of the seasons, and the slower and more durable effects of climate as modifying diseases of a restricted habitat. The last cause concerns the diseases brought about directly or indirectly by vicious ali- mentation. There are no diseases peculiar to the soldier; but military conditions are frequently such, particularly during a campaign, that the germs of disease are widely disseminated among an especially susceptible body of men — and hence a larger number are attacked and succumb than would probably have been the case in civil life. In character, the diseases developed in the military establishment call for no remark unless it be their unusually severe type, the regularity with which outbreaks of some affections recur, and the frequent tendency of others to become endemoepidemic. The prevailing diseases in armies 592 REFERENCE HANDBOOK "1 THE MEDICAL SCIENCES Army Medical Statistics are, naturally, largely acute; and a large propor- tion of thein arc zymotic and hence theoretically preventable. I he purpose of army medical statistics i- to define the influence of military life upon health and ti> per- mit the ready appreciation and accurate comparison of varying conditions of service and environment in their relation to the well-being of the soldier. Since each case of sickness in the military establish- ment at once becomes a matter of official record at the hands of competent observers, it follows that statistics so obtained are not only more comprehen- bul more accurate than those bearing on the irrence of disease among civilians. Unfortu- v tor their general utility, however, they are i upon a physically superior class, always exist- under restricted and unusual conditions and fre- 1 1 v in unfavorable surroundings, and hence ictions which may be drawn from them cannot legitimately applied outside the limits of the military service. Unfortunately, also, owing to the irent systems of nomenclature and classification eases which have prevailed in the past, as well other causes which will be referred to later, it i< not always possible accurately to compare the sickness and mortality from special causes occurring in differ- annies, or even for the military establishment and civilian classes of the same nation. The commit- on international military medical statistics which met at Budapest in 1894 has, however, formulated a plan which overcomes in great measure the difficul- ties with which army statisticians have had to con- tend, leads to a common basis of comparison, and will ultimately be the means of affording a large amount of information hitherto not available. In the British army, statistics with regard to sick- and mortality were first compiled shortly after the close of the Peninsular war, but were published at long and irregular intervals. They gave much information with regard to the healthfulness of various stations, but the advent of the Crimean war caused their temporary discontinuance. In 1S59 their publication was again resumed and they have since been issued annually. Army statistics have collected in France and Germany since the Napoleonic wars, but have not been regularly made available for general use, frequently being issued only in part or not at all. Of late years, France has not given out full information as to the occurrence of ase and death among her military forces. In the Itiited States army, satisfactory data for the period prior to 1S40 are not available, and it is only since Iss-t that figures sufficiently elaborate to be of any great value to the statistician have been compiled and published. At present the official returns show not only the amount of loss the army annually incurs from disease but also the causes leading thereto as influenced by race, age, length of service, arm. of service, season, station, and other factors. Little information is gained by recording the statis- tics of disease as a whole, since so many factors com- bine in the production of the final result that they must be separately studied to arrive at a proper ^standing of the whole. The main points upon which army medical statistics are based are as follows: 1. The number of admissions to sick report as compared with the number of persons furnishing the This is accomplished by taking the actual lumbers in both classes and reducing them to a com- parable standard in rates per "thousand. The lumbers furnishing the sick are reduced by those sick in quarters or hospital; but as a general rule an equivalent number of men are returned to duty or 1 ulisted to replace the losses through death or 'Usability. In our service statistics are based on ital strength. 2. The rate of deaths per thousand strength. This Vol. I. — 38 is obtained by the division of the total number of CUrring during the year by the mean at Qua] strength, including the absent as well a rving with the colors. The figures thus obtained are then reduced to rates per thousand. .'). The rate of discharges for disability from dis- ease, per thousand strength — obtained by dividing the losses from discharge by the i • ngth and then reducing to the above standard of comparison. 1. The total ln-rs from disea-e; as determined by the sum of the rates for mortality and for discharge for disability from this cause. 5. The rate of constant sickness, or constant ineffi- ciency. This is given by adding the numbers put down as remaining under treatment at the end of each week, or month and dividing by the number of days, weeks, or months in the period desired, again reducing to the comparable standard. 6. The number of days of service lost by each soldier. This is found by adding together the total number of sick days in a given period and dividing by the mean strength of the command for that period. In all computations the figures are reduced to common terms of one year and one thousand strength. Comparative Loss in C from Sich d Wounds. — Since the great military epidemics of antiq- uity — the destruction of the Assyrians under Sen- nacherib; the plague described as occurring during the Peloponnesian war; the pestilences which ravaged the Roman and Carthaginian armies; the great losses substained by the army of Severus in the mar- shes of Caledonia — it has been established as a gen- eral rule that, in protracted wars, armies suffer much less from wounds than from disease. The con- stant advance in sanitation, however, based upon an accurate knowledge of etiological factors, has exerted a marked effect in diminishing military mor- bidity and mortality; and while in the future a com- paratively high sick and death rate among troops engaged in war is always to be expected, it is scarcely possible that such disastrous epidemics as have prevailed in times gone by could be repeated in the future. Wars become shorter as they become, through modern refinements, more expensive; and troops, particularly in an aggressive and decisive campaign, are not exposed to unhealthful influences to as great a degree as was the case when hostilities were more protracted. With improvement in the effectiveness of arms, as regards both range and ra- pidity of action, the proportion of casualty for any period of action must naturally be increased — and hence there is a constant tendency toward the approximation of the rates from wounds and disease. From the records of the past, however, many valu- able lessons can still be drawn. In 1809, during the Walcheren expedition, the mortality in the British army from disease was 346.9 per thousand effectives, while only 16.7 per thousand were killed by the enemy. A few j-ears later the British army in Spain lost three times as many men by disease as by the result of con- flict, and the sick rate mounted to such proportions that more than twice the number of men composing the army passed through the hospitals during a sin- gle year. In the Russian campaign against Turkey, in 1828, it was estimated that SO, 000 men died of disease and "20,000 in consequence of wounds. During ( teneral Scott's campaign in Mexico the losses from disease alone exceeded thirty-three per cent, of the effective strength of the forces under his command, and in a single regiment of Indiana volunteers which entered the service 1.000 strong only 400 re- turned to the State for muster out. Laveran states that in the Crimean war the allies [osl 52,000 men in six months, of which number 50,000 men were un- harmed by the Russians; while during the entire war, according to Viry, the French lost, in round numbers, out of a total force of 300,900 men, no less than 95,000, of whom 75,000 died of disease and only 593 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES 20,000 died on the field or succumbed to wounds. In this campaign nearly one-fourth of the French medical officers arc said to have succumbed to sickness. During the war in Italy, in 1859, a period of hostilities of only short duration, there were from the French force of 200,000 men. 129,950 admissions to hospital. In the war carried on by France in Mexico the mor- tality from gunshot and that from sickness was as 10 to !",). The mortality among the Fnited States forces in the Civil war was divided as follows: Mortality. White. Colored. Total. 42,721 I7.au 157,004 23,347 1,514 1,817 29,212 S37 44 238 19,731 24,184 Total 270,989 33,380 304,369 From the most reliable data available the deaths in the armies of the Confederate States during this struggle did not fall short of 200,000, three-fourths of which number were due to disease and one-fourth to the casualties of battle. In 1866, in the war against Austria, out of a total strength of 437,260, the Prussians lost in an unusually brief and decisive campaign ii,427 men by sickness and 4,450 at the hands of the enemy. The Franco- German war, in 1870-71, furnished the only exception up to the time of the Russo-Japanese war, to tin' general rule that more men are killed by disease than by the weapons of the enemy, since of the German army 33.7 per thousand strength fell in battle while only 18.6 per thousand died of disease. This admir- able result was largely due to the proper observance of sanitary precautions; assisted, no doubt, by the brevity of the campaign, the rapidity of the move- ments, and the fact that active operations were con- ducted during the most healthful season of the year. In the Russo-Turkish war of 1878, according to Viry, the Russians lost 102,799 men, of whom only 10,578 were killed by the enemy. During the Spanish- American war of 1898, for the five months which in- cluded the total period of hostilities, of the 274,717 officers and men enrolled in the United States forces there were only 34.5 men killed by the enemy while 2,565 succumbed to disease. For the whole year of 1S9S the deaths from wounds in our service gave a rate of 0.G2 per thousand strength, the killed in battle amounted to 2.79 per thousand strength, while the deaths from all causes aggregated 30.31 per thousand. Even in July, the month in which aggressive opera- tions against Santiago were conducted, the killed in action amounted to only 1.25 per thousand, while the deaths from disease were 1.7S per thousand. The British in the last South African war, had 7411.0 admissions per thousand from disease and but 34.0 per thousand for wounds inflicted by the enemy; while the deaths from disease were 09.0 per thousand and deaths of those killed in action or sub- sequently dying of wounds amounted to but 12.0 per thousand. But the Japanese Army reversed tliis in the Russo-Japanese war, the best available statistics giving their killed at 72.0 per thousand Strength; their wounded at 266.8; and their deaths from disease at lis per thousand strength. An interesting side light on the later results of hard campaigning is given by Rosse, in his statement thai of the old soldiers carried on the Fnited State. pension rolls those disabled by disease are more than four times greater in number than those pensioned for wounds. Death Rates in Civil ami Military Life. — The diffi- 594 culties attending an accurate comparison of death rates for the military service and those of civil 'life are necessarily very great. Owing to the rejection of intending recruit- many individuals are at once returned to private life whose early demise would otherwise have gone to swell the military death rates Further, the army is maintained as a s"elect body of physically sound men, and its weaklings are constantly undergoing elimination from the service ultimately to increase the mortality of civil life. Hence civilian rates are unduly increased, while army statis- t ics fail to show all the deaths presumably due to mili- tary service — and it is obvious that the more rigorously the standard for the soldier is maintained as regard's physical excellence, the more favorable the showing apparently made for a military life. Vallin, in France in L871, placed the probable error due to the above causes at as much as 9.19 per thousand, thus practi- cally doubling the figures for the military death ri of his time. Viry considered this allowance to be too high, but believed that a rate of 3.60 per thousand, for such as leave the colors with incurable disease should be added to the military and subtracted from the civilian death rates; thus making a difference of 7.20 per thousand. The estimates of Marvaud placed the probable error at four per thousand. While it is probably correct for the French service to add 3 60 or even four per thousand to the millitary death rate, to deduct the same number from the civilian rate involves the broad assumption that the numbers in each class exactly correspond. For our own service the immense disproportion existing between the pres- ent small army of 75,000 men and the large number of males of the military age living in the United States renders the influence of the comparativi ly small number of soldiers who may be discharged for incurable disease upon the civilian death rate of so little importance that it may practically be disre- garded. The census returns for 1S80 give the an death rate for disease as 6.97 per thousand for all males between the ages of twenty and forty-five yi During the same year the mortality from disease in the United States army was 5.S8 per thousand — appar- ently a distinct advantage in favor of the military service. If, however, Viry 's factor above mentic be accepted as correct for our service, the true mili- tary mortality becomes 9.48, or 2.51 per thousand in excess of the civilian rate for the same period. As it is probable that since that time the death rate in the military service has diminished in proportionately greater degree than has been the case in civil life, it may be fairly assumed that, under conditions of peace, the death rate in our army is at present but slightly in excess of the mortality for the same in civil life. The results obtained by Farr in his com- parison of the death rate in the British army with the corresponding classes of civil life, made a genera- tion ago, are as follows: Death rate Age. per 1,000, 20-25. — Soldiers 17.0 Civilians 8.4 25 30. — Soldiers IS. 3 Civilians . !>.2 30-35.— Soldiers Is. i Civilians 10.3 35-40. — Soldiers I'LL' Civilians .11.6 According to Notter and Firth, the present death rate of the civil male population in England, at the soldier's age, is as follows: Morta Age. per I I -'11 25 5. I 25-35 7.1 ; i 15 i-' 3 Between the ages of twenty and thirty-four the mortality is in favor of the soldier, but after thirty- REFERKXCK HAXDBOOK OF THE MEDICAL SCIENCES Army Medical Statistics the mortality is reversed and the civil rates are ower. [■'or (lie British service I lie death rate for the home ons was 3.42 per thousand in 1897 and l.iis per fiousand for the decade IS87-1896. If the civilian leath rate for all males of the military age be accepted i- about seven per thousand, the showing made com- iares favorably with similar figures for the German in and is superior to the French mortality rates. I'liis is certainly a great improvement over the con- ns existing in 1856, when it was shown that the mortality in the army at large was twice as great as ong the civilian population, and in the case of the I luards three limes as great. gards t he < lerman army, it was recently stated iv its surgeon-general that during the early part of century the death rale of the male civil populat- ion of Prussia, between twenty and thirty years of . was lower than that of the military death rate, figures being fourteen per thousand for the army ind ten per thousand for the civil population. This lit ion is now reversed, and in 1S93 the death rate i Prussia for the civil male population from twenty to thirty years of age was 6.38 per thousand, while at the same time the mortality for the German army ;.(ili per thousand. While these results are cer- tainly admirable and are undoubtedly in large part due to careful observance of sanitary regulations, u should be remembered that soldiers unable to main- tain the required physical standard are probably more thoroughly eliminated in the German army, and at an earlier period in their military training, than in other services. In the French army, on the home stations, the age annual death rate from 1882 to 1890, inclu- was 7.88 per thousand strength; while Bertil- fixed the annual mortality among the civilian male population, between the ages of twenty and ity-five at 10.60 per thousand. Marvaud, how- , believed that the estimate made by Bertillon was too low, and placed the annual death rate for civilians of the military age at two per thousand. nig Marvaud's coefficient of error given above, the corrected rate for the French military service would become 11.88, while it would be eight per thousand for the same class in civil life. Marvaud concludes "that, in spite of all ameliorations which have been introduced, chiefly of late years, into the hygienical Surroundings of the French soldier, his mortality rate is ^t ill elevated and certainly exceeds that of the same sex and age in civil life." Loss of Time from Sickness. — In the United States service the annual average number of days lo s,-s. United States 1,043.43 30.74 12.98 3 . 96 16.94 962.05 26 87 1 1 52 .',. 16 111 MS ( lermany . . . sio, to 24 . 67 13.20 4.11 17.34 907 . 1 1 2 ; 16 12.46 4 . 'J6 16.72 1,033.14 32.81 18.87 4.16 23.03 Scandinavia . 8S6.08 26 - 55 13 3 : 5.17 18.50 Scotland S52.38 25 64 12.50 1. 17 13.97 Switzerland. . 893.75 27 82 12.31 2 . 90 15.11 Austria 807.1 1 21.63 16.53 2.67 19.20 1 tanmark. . . s ;r, o:; 26.21 13.33 5 . 55 18.82 t'i 1,049. 13 30.89 in 56 7 04 17.68 Ail others.. . . 821. 12 23 . 90 13.66 3.86 15.70 595 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES It should be noted, however, that the figures given fur the countries named in the latter half of the above table are not to be considered as absolute, since they are not based upon a sufficiently large number of men to avoid the possibility of error. These rates are, however, of particular interest, since, so far as they go, they tend to bear out the popular belief that the native-born American possesses a greater proportion of vital force and greater power of resistance against death than does the foreigner. Race proclivity, as regards sickness, is well shown by the records of the British forces in the West Indies, in which, for the ten years 1876—1885, the ad- missions per thousand of strength for the whites were 893.5, colored 1,(174.1; discharges, whites 13.95, colored 26.79; constantly non-effective, whites 44.68, colored 58.38; deaths, whites 1.3.42, colored 15.38. In the United States service, for the decade 1877-80, the death rate among the whites per thousand was 9.97 and for the colored 12.91. There has been, however, a constant tendency for the past twenty years toward the approximation of the rates for the whites and blacks in our service; and therelative rates per thousand for the white troops of all nation- alities as compared with those for the colored troops, during the year 1S97, were as follows: Admis- sions to hospital. Constantly non- effective. Discharges for disability. Deaths Total losses. 35.72 37.24 11.04 10. S9 9.62 9.51 5.05 5.89 14.67 15.40 But since the Spanish war, new factors of climate, environment, and race have entered. For the year 1910, some rates per thousand were as follows: Whites, in United States Colored, in United States Whites, in Philippines Filipino native scouts. Admis- Con- sions to stantly ,n hospital. non- c3 effective Q 1 lis- charges. 903.31 827.53 1,242.65 S76.10 34.25 4.25 2.S . 72 7.37 45. 15 5.19 26.01 4.31 15.45 12.39 10.14 6.79 Total losses. 19.70 19.76 1 J . 23 11.13 The lower rate for losses in the Philippines is ex- plained by the practice of sending home to the United States many serious cases for treatment or discharge for disability. In the distribution of diseases according to nativity, typhoid fever and rheumatic fever had their greatest prevalence in our service, for the years 1890-1S96, among the Canadians and Scandinavians. The high- <■ l admission rates for consumption were 5.70 among the French and 4.76 among the Scotch; the lowest rates were 1.42 among the English and 1.49 among the Germans, the rate among the nativesof the United States being 3.33. Pneumonia was more frequent among Canadians, 5. IS, and Scotch, 4.76, than in men of other nativities. The rate for this disease for the natives of the United States was 3.90. Venereal disease prevailed more among men born in the United Stales and Canada than among the others, the admission rates for these two classes being 93.98 and 91.92 respectively; the Irish and Swiss had the lowest rates, 47.00 and 50.90. The Irish, however, had by far the largest relative number of cases of alcoholism, 90.96. The smallesl rales for this cause were given by the Danes, 12.59, and Austrians, 19.00; the admission rate for the native-born American soldier having been 28.51 for this cause. Sickness and Death Rates as Affected by Season. .Military morbidity and mortality are to a certain extent influenced by seasonal changes; varying accord- ing to the climatic conditions prevailing in each country or locality, by which the propagation of certain affections is either favored or retarded. In the French army the admissions to hospital for disease in time of peace, reach the maximum of fifty-seven or fifty-eight in January and fall to the minimum of about thirty-eight per thousand in September. In the Italian army, for the period 1872-1S92, the great- est amount of sickness occurred in March and the least in November. In the United States service the midsummer period is the most unhealthful, while the late fall and early winter gives the least sickness. The monthly prevalence of disease in our army, in time of peace, as given in the figures for the year i vi_>, is shown in the following table: Total admissions to hospital, per thou- sand of mean strength, for dis- ease and injury. Constantly non-ef- fective, per thou- sand of in . : . strength, from dis- ease and injury. January. . . February. . March April May June July August. . . . September October. . . November. December. 148.65 107. S7 108.03 92 . 53 9S.66 101.94 108.26 108.37 108.57 97.48 91.97 9S.34 49.54 41.69 39.27 37.34 37.67 :;s.3i 37 . 46 36. S6 38. 12 38.79 39.38 111.44 For the year 1898, when the army, if not entirely engaged in active military operations, was, after the month of March, still in the field and on a war footing, the monthly rates per thousand strength were as follows: January. . . February. . March April May June July August. . . . September October. . . \i -\ . ■ T r l I XT, December. Admissions from disease. Discharges from
  • t year and under. . . Second year Third year Fourth year Fifth year Six1 h year N '. i nth year Eighth year Ninth year. Tenth year Twelfth year Fifteenth year and over ,205 ,632 ,645 ,2 I'J ,053 ,148 897 629 738 921 ,351 ,587 2,254 l.t «1 98 1 967 1,064 901 97IJ 1,057 927 991 1,007 823 For the same year the discharges for disability, divided according to length of service, were as follows: Discharges for Service. disability, per 1,000 strength. Under 1 year 64.9 1 year ... .41.5 2 years . 3 years . 4 years . 5 years 6 years . 7 years . 8 years . 9 years . 10 years . 12 years 13.3 19. 6 2.3.1 15 years and over 22 . 1 For the same year the death rate per thousand strength, according to length of service, was deter- mined to be: Less than one year of service 10.90 One year of service 4. SO First five years of service 4.54 Second five years of ser\ice 5 . 22 While the absolute number of men in the army of the United States during the year 1SS5 can scarcely be considered as sufficiently large to warrant any exact deductions, it is certainly safe to assume that the processes of elimination in our army are most active by far during the first twelve months of service; after which the total losses fall below the general rate for the whole army, not to rise again until the more mature men of ten years' or longer service succumb to infirmity. Viry states that in the French service the annual losses by death and discharge for disability amount approximately to forty per thousand during the first year of service, thirty per thousand during the second year with the colors, and twenty during each of the subsequent years. According to Ordronaux, sta- tistics for the French army some years ago showed the following to be the average annual mortality: Service. 1 year 2 years ears 4 years 4.3 5 years 3.0 6 years 2.0 7 years 2.0 In comparing the amount of sickness among French soldiers of one year of service with those of two or three, Viry found that in 1888 there were, per thou- and of each class, 866 admissions among the former and 132 among the hitter: in 1889 the numbers were 859 and is:;, and in 1890 they were 826 and 5.59 respect ively. The proportionate mortality in the German army for the year 1889-90, out of each 1,000 deaths, was as follows: Loss per 1 .111)0. 7.5 6.5 5.2 Less than 1 year of service. . From 1 to 2 years' service. . . From 2 to 3 years' service. . . From 3 to 4 years' service. . . 4 years' service and upward, 432.0 248.0 143.8 29.5 146.7 Total 1,000.0 In the discharges for disability in the German army for the same year, out of 8,740 men so discha 78.3 per cent, owed their incapacity for service to causes existing prior to enlistment. Hence it is not surprising that the majority of men so discharged should have been less than one year with the colors. The percentage of discharges according to length of service was as follows: First year SI. 4 Second ye:tr 8.6 Third year 5.0 Fourth year 2.0 Under conditions of tropical service the raw and unseasoned recruits are proportionately even more prone to disease than is the case in temperate cli- mates, as is well shown in the following rates for the British troops in India during the year 1897. bV ■ a o GO 'a CJ c — > Ratios per 1,000 streng h Length of service in India Admis- sions. Deaths. 1 e i 5 to 10 years 10 years and up- 1 1 6 10 11,580 11,368 8.013 8,874 1,806 1.111 21,700 18,795 17,929 14,866 10,548 11,728 1 222 36 311 217 20S 124 131 151 31 8 302 123 477. 446 265 288 59 1857.9 29. 15 25 86 1G23. 1 is. 7 . 16.53 1 77.1 1 ;.30 11.78 1472.0 12. 2S 14.16 1316. 1 16 :; 1321 .6 17.02 32. IS G76.fi 17. 17 Not stated 32 1 7.20 Total 61,531 96,824 1,214 2.25S 1500.4 IS. SI 31.99 1 Age as Influencing Sickness and Mortality. — In the United States service, for the seven year* 189(1 IXOfi inclusive, the relation between disease and age among the enlisted strength existed as follows: 3 e u4 © © ■£ S S J3 p , ■s - « o o u .£ § H o>n 7 ' » c £ a a ■a — a c u a c Age. ■ - — - t- tf » - *4 £ la -a g-S i.{ '■*> S z. ba *i to *J w a i. _ i a — - *- -.2 3 Admi hospi dise 1,000 z z - non- from 1,000 .£ ' - '- — - °o 7 S 7S g Q^q 19 years and less. 2,244.79 69.73 ■ 61 5 3 ' 20 to 24 years I. 159 6 : 39 52 11. 12 2 ' : 25 i" 29 years. . . . S96.6.5 20.06 11.96 : 1 ; 3 i ( " -1 years, . . . 755.64 21 53 l:i 69 :: 7 ; 35 to 39 years. . . . 718.43 21.32 L0.32 4 . 32 40 to 4 1 years. . . . 798.09 24.87 L6 65 7.46 24.11 755.01 21.16 1 5 . 26 10.97 50 to 54 years. . . . 843. is 28 96 31.11 13.18 1 55 i o 59 years. , , . 875.22 34.93 1 5 60 years and over. 1.265.31 72.91 1-'2.01 66.04 188.68 The younger men, both officers and soldiers, appear particularly susceptible to disease as well as prone to injury. For the period noted above typhoid ft v as observed to be much more prevalent among 1 1 under thirty years of age. The rate for this dist B in men from twenty to twenty-four years of age WM 10.31; from twenty-five to twenty-nine years, .".71; from thirty to thirty-four years, 2.58. Enlisted men under twenty-five years of age suffered more from malarial fevers than did officers of the same age; but with the advance of years the rates of the came to differ but little from those of their superiors. 598 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Statistics |,e higher rates for venereal disease were given bj nder thirty and particularly by those under i-enty-five years of as;' 1 ; but, on the other hand, the r alcoholism increased with age. Tuberculo- : appeared to be equally distributed among men the ages of twenty and fifty years, hut the [iarrheal troubles was confined to soldiers twenty-five years. Rheumatic fever was , H ,t lly prevalent among young men, susceptibility eing increased after the age of forty or fifty years. or pneumonia were considerably larger five years of age — as were also tho idney disease. In the French army, for the decade 1875-1884, pei trength, the average annual death rate for all given by Marvaud, was: Under 20 years <>f age 6.72 oi age 10.92 irs of age 9.38 o 26 years of age 8.59 o 30 years of age 7.14 Fta ■ ears of age 8.51 'he cla.ss less than twenty years old is not only a iv small one, amounting, according to Bertillon, • only about three per cent, of the whole, but the oung men composing it are all volunteers and before ut are subjected to an exceptionally severe il examination, so that only the best ii\< - are ccepted. Hence for the French army at large the ar of service may be considered to begin at the iventy to twenty-two years. In commenting ii the excessive mortality of the younger soldiers, larvaud says: "It is during the first year of service mber of deaths attains its maximum, a act which proves the dangers provoked by acclima- ion to a military life." The influence of age upon ickness, in time of war, is even more marked than luring peace. According to Gayet,. in the cam- laign of Benin the total losses by deaths and disease repatriation were as follow-: Per cent. Foreign legion 9.7 Artillery of the marine 23.3 21.2 Infantry of the marine 39.0 African battalion 47.9 in the lasl two classes the men were young and v developed, ranging from nineteen to twenty-two rears of age; in the foreign legion the men were older, >eing between the ages of twenty-five and thirty-five of Military Rank as Affecting Health. — The report of the surgeon-general for 1897 gives statistics for our army to include the seven years 1S90-1S96, this being equivalent to a total strength 'or one year of 14,859 officers and 17 1,'Jss enlisted men. These figures show a sick rate of 76.5.69 per ad for the officers and 1.25S.90 for the men; nut the inefficiency rate of the former class was much than that of the latter, being 44.27 per nd as compared with 37.63 per thousand in the t In 1 enlisted force. The average death rate for was 9.56 per thousand, while among the en- listed men the annual mortality was only 6.52 per '»1. Such an unfavorable showing made by the officers as regards the rates for death and ineffi- i iency is largely to be explained by the fact that the military life of the enlisted soldier practically ceases at the age of forty-four years, only 6.50 per cent, of this class remaining in service after that ace; while ii the officers included in the tabulation referred to, 37.25 per cent, were over forty-four years of age. liter class, then, while sharing largely with the 1 men in the hygienic disadvantages of im- maturity, had, in addition, the diseases of beginning 'ml age and the results of long years of hard service tn increase its death rate. It 'is to be noted that during this same period young officers under twenty- five years had only 784.20 admissions per thousand for disease, w here thi id an admission rate <>f 1,359.63; while the nor taie oi t he former was 29.61, a- compared with t he rate of 39.52 for the hitter. This would indicate thai if the same attention "as given to sanitary details by the young soldier as by the young officer, hi- rate of constant -ickness would be corn pondingly reduced. The influence of petty rank ami length of service on sickness in the French tinny is shown in the -lib- joined table, constructei 1 hum data given by Marvaud covering the year 1S88: per 1 ,000 i in 260 567 Men having more than one year of service Men h:iviiij_' [i 1 yeai of service.. 172 2S9 The proportionately large number of non-conn sioned officers treated in hospital is explained by Marvaud as being due to lack of suitable accommoda- tions in the detention rooms for this class. Health of Troops in Peace. — The individual signifi- cance of the several factors which, taken together, determine the sanitary condition of our army in time of peace will be readily appreciated by reference to the subjoined table. Venereal affections have the high- .-t admission rate for sickness, but the mortality from this cause is not great. Malarial diseases rank second in frequency, but. as shown by statistics, they tire not of severe type and are readily amenable to treatment. Pneumonia occupies third place in importance as re- gards admissions. Rheumatism and myalgia together furnish a large proportion of admission- and dis- charges, as does also bronchitis. The admissions for alcoholism are slightly above the general mean, but the rates for death and non-efficiency from this cause are small. All the rates for typhoid fever are low. As to injuries, the several figures for contusions and sprains are all large — those for wounds, excluding gunshot injuries, being considerably lower than'those for contusions, but still somewhat in excess of the general average. But since our Colonial expansion, our troops have become exposed to many morbid influences, practically or entirely absent from this country. The effect of these diseases in altering siek rates is shown in the following table for the year 1909. With regard to sickness, deaths, and non-efficiency in the British service for the home stations, the fact which at once attracts attention is the high ratio given by venereal affections; the admissions from this <• being more than half again as high as from any other affection or group of diseases. For gonorrhea, primary and tertiary syphilis, the individual rates for non-efficiency are much higher than for such disi as are summarized as affections of the respiratory and tive systems. The rates for rheumatism and influenza are high, while diseases of the -kin and of the connective tissue are common. Alcoholism is a mi- nor factor in increasing the- rates for sickness, deaths, and non-efficiency. Decreast in Rates under Conditions of Peace. — That improvement in the sanitary administration and state of armies is constantly being made will be unhesitat- ingly admitted, but few are aware of the stupendous progress in this respect which, particularly during the pasl generation, lias been accomplished by military hygiene. Not only is this the case in our own service, but in foreign armies also, and, on reviewing the sanitary conditions which for their time were consid- ered to be excellent, it is apparent that -till further decrease in the several rates may justly be anticipated for the future. 599 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Table of Admission's to Sick Report. Discharges. Deaths, and Nov- effectiveness, with Ratio? per 1.000 of Mean- •Strength, fob the Abut — Officers axd Total Enlisted — For the Year 1909. Officers U. S. Army. American troops, army. Mean strength. 522— A. G. • >., 74.319— A. G. O.. 75,399. Causes of admission to sick report. Retirement Admissions, for disa- bility. Deaths. Xon-effective. Admissions. Discharges. Deaths. *" m - Ratio. N ; um - lurio N ; um - Ratio b3T. ber. *"***" ber. T" m - Ratio. N ^ m - Batio. ber. ber. *" m - Ratio "?° m - Ratio ber. ber. Xon-effe<-ive. Num- ber. Ratio. Typhoid fever, in- cluding P phoid fever Fevers, undetermined Malarial fevers Intermittent Estivo-autumnal Malarial cachexia, and undeter- mined infection. Smallpox. ... Measles Scarlet fever Diphtheria Influenza Cholera nostras Dysentery Amebic Bacillary. . Mixed infections and other dys- enteries Leprosy Beriberi.. . . Erysipelas.. . Dengue Mumps Cerebrospinal men- ingitis, epidemic *. . . Purulent infection and septicemia. . Trichino-i- Tuberculosis Tuberculosis, pul- monary . . . . Tuberculo-i - othei Venereal disei .Syphilis and its resu!-. Chancroid and its resul'- Gonorrhea a r and other malignant growths. . Rheumatism, artic- ular Rheumatic fever. . Rheumatism, sub- acute and chronic, artic- ular. . . Alcoholism and its I Epilepsy Trachor:.:: earl Filari.'i- Chyluria. 11 _ 12 3.14 . 102 26.69 . 63 1 S.63 . 6 1.57 . 1 1 - 195 51.02 . . . 18 12 2 4.71 3.14 4 1.05 3 .73 93 24.33 . 7 1.S3 . 12 11 1 3! 18 10 23 2 1 1 11 1 1 3.14 3 2 - - - 1.05 . 6.02 . 4.71 .... 2 . r,2 2.09 6.02 - .26 .26 0.23 .47 : . 17 2 .47 1 .23 2.53 3.02 1.16 1.43 0.67 267 470 2,855 2,096 560 99 .04 .19 .01 .05 3.61 " 2.65 .69 2.21 .24 .06 580 2 35 2.00S _ 675 319 155 .21 .07 : 88 .29 .02 .49 .08 .01 .24 .001 .07 11.39 2.98 10.96 . 57 .43 .11 3.12 0.82 201 3 31 1,695 72 14 11 1 3."* : .40 - .S9 1. 17 .42 .62 .54 .01 2.44 .50 .02 .23 .10 _ •: : 'i.090 .2:; .11 10 .2S 413 .16 1 77" .14 . .001 .07 _ .61 ^7 .13 9 .004 2 ' 3.59 6.32 ■ - 29.55 1.33 .03 1 .01 19 2 0.25 .03 .03 .31 .47 27 . .o:; - i 3 1 .11 .01 .04 .01 9. OS 4.20 2.09 : - 6 5 1 .19 .04 .OS .07 .01 .01 .04 - .03 - 1 .01 2 1 .03 .01 9.69 .19 .01 15.20 .15 .01 - 1 .03 .01 S 5 .11 .07 - " 4.00 .71 196.99 30.45 77 n 171 160 1, 206 122 - - 2.12 - " 1.11 43 35 S .57 .46 .11 .13 13.1'' .05 .34 .03 5.56 I 1.61 1.74 .43 2.52 .12 .03 .01 24 .32 22 .29 109 1.43 4 .05 .01 .01 69 6 .91 .OS 26 3 .09 .01 .34 .04 47.71 0.64 22 .10 62. 3S .84 42.90 .58 15.00 .20 1.4S - 36.19 1.90 1.90 31.97 - 57.16 35.05 12.05 10.06 2.13 .50 1.64 30.32 1.57 .42 17.20 1.05 201.93 .06 .003 .49 .03 .03 .43 .0003 "- 1 .16 .14 .03 .01 .02 .40 .41 .02 .01 .01 .004 - 191.0. 2 " 10.91 - - .. • 134.67 610.75 .15 13.07 3.04 .02 .91 34.46 .46 33.63 .45 21.07 10.46 3.69 24.16 .31 .28 .14 .05 .003 GOO REFERENCE HANDBOOK "I" THE MEDICAL SCIENi Army Medical MatlMi«.» Table or A Repokt, Discharges, Deaths, and X StBE.VOTH, POB THE ARMY — OpFICERS i Officers V. S. Army. Mean strength . 74.319 Admi - for disa- bility. Deaths. Non-effective Admiasi - I 1 schargi I ■• Non-effe Causes of admission port. Num- ber. Ratio. N " um " Ratio N " um ' Ratio N *™- ber. ber. ber. S »"'- Ratio. N ; un '- Ratio *"■" ber. ber. Num- ber. Ratio. Ly m phalli eKpli (ever Other filai of the heart . . Bronchitis. acute and chronic Bronchopneumonia Pneumonia I pneu- •iic fever... Diarrhea and en- teriti- Tenia Tenia sohum Hymenal nan l Bothn<>cephalus latus ris Jumbri- . ■ .ris vermic- ularis mum duodenal-- Necaior Aineri- canus Other intestinal parasite- Inguinal and other hernia? Hepatic abscess Appen-li' - Climatic bub Tropical ulcer \ pene- - Pemphigus con- tagi»- 1~ Dhobie itch Tenia imbric; Prickly heat ■ ■-.'■- is Chronic nephritic. . . Malingering External causes, special. Fractures, exclusive of gunshot Dislf>ca*i ins Sprains and muscular strains Wounds, gui Wounds, other than gunhsot ■ ke Frostbite and general freezing Drowning. . ing, acute ►us bites, etc - bite Other venomous bites, etc .78 155 40.55 3 .78 1.05 23 1 7 1 .45 1 .26 1 .26 12 3.14 .52 31 S.ll 120 31.40 5 1.31 42 10.99 1 .26 12 3.14 S 2.09 S 2.09 ! 1 21 5.49 I 34 8.90 12 3.14 - .70 .004 .1" 62 .06 .10 1 2.521 21 1.34 .01 .01 2.71 . 55 1.97 . 06 .001 .001 .71 .14 1.30 .07 .64 4.13 1.08 .99 .26 4.1.5 1.09 1.05 .03 .41 .01 .001 4 19 136 127 1 22 ■ 7 23 10 49 212 10 20 15 70 S04 21d 215 - 7 85 .19 .09 .05 .02 .09 .02 315 86 84 .HI .28 . i .54 2.-507 .01 5.21 .002 65 1 31 .12 .03 .05 -.26 .03 1.83 1.71 .01 3.61 .30 ! .09 .31 .13 _ .61 .94 10.82 2.95 56.92 - 43.30 .09 1.14 1.16 .03 1.13 32 1 18 01 .13 24 .21 01 51 7 .32 .09 04 28 11 .1.5 11.79 1 08 . i; .12 .03 .01 29.13 ■ 33.58 0004 .16 12.16 .16 52 .10 .01 .01 .002 .0004 .01 .0003 .03 .03 .0001 .40 .06 .4.5 .01 1.11 .02 .21 .003 1 . 55 .02 4.63 .06 . 15 .002 .005 3.6.5 .0.5 7 5 .10 .03 99.33 1.34 10.16 .14 1.20 24.63 .33 79.01 1.06 .36 .004 2.10 .03 .hi 1.50 .02 .09 .001 601 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Tabls of Admissions to Sick Report, Discharges, Deaths, axd Non-effectiveness, with Ratios per 1,000 of Mean riTREXGTH, FOR THE AflMY OFFICERS AND TOTAL ENLISTED FuR THE YEAR 1900. Continued. Officers U S. Army. American troops, army. S. G. 0., 1,822 -A. G. O., 4.2S3. S. G ii.. 74,316- -A. G. ' ' , 75.399. Causes of admission Admissions. Retirement for disa- bility. Deaths. Non-effective. Admissions. Discharges. I It'aths. Non-effective. to sick report. Num- ber. Ratio. Num- ber. Ratio N u um " Ratio ber. Num- ber. Ratio Num- ber. Ratio. Num- ber. Ratio Num- ber. Ratio Num- ber. Ratio. Diseases find '"- juries grouped. Infectious diseases Other general Diseases of the nerv- ous organs of special 544 439 105 188 102 60 20 59 314 601 52 120 99 142 33 114. S6 27. 17 19.19 26.69 17.27 5.23 15.44 82.16 157.25 13.61 31 . m 25 . 90 S 3 5 15 13 2 13 1.87 71) 1.17 3 3.04 .47 : 04 4 1 :: 2 2 .93 .23 .70 . 17 . 17 34 . 03 14.35 19.68 17. I-", 12.70 2.77 1 92 5.11 7.33 19.13 4 . 53 5.89 4.08 8 90 3.75 5.15 4.57 3.34 .72 .50 1.34 1 .92 5.00 1.18 1 . 5 1 1 .07 28,396 10.3S7 IS, 009 2,955 1.253 1,121 5S1 1,681 5,209 14,812 1,050 6,512 2,308 130 1 1,300 382.08 139.76 242.32 39.76 16.86 IS. OS 7.S2 22.62 70.09 199.30 14.13 S7.62 31.06 1 . 75 .01 17.49 476 11 465 2S0 220 32 28 112 33 72 51 9 41 71 6.31 .15 6.17 3.71 2.92 . 12 .37 1.49 . 11 .95 .68 .12 .5 1 -.94 121 60 01 10 10 1.60 .SO .81 .13 .13 1,612.09 ■ . ■ . 1,284. 12 1 5:; . :i i si. id 39.96 r>g 22 in ;. ill 115.44 317.80 49.63 170.09 80.42 12.84 .02 21.69 4.41 17.28 2.06 Of the nervous 1.13 Of the eye and its .54 Of the ear and its .39 Diseases of th latory system. . Diseases ol iherespir- 3 .70 33 29 22 12 .44 .38 .29 .16 1.39 1.55 Diseases of the diges- tive system Diseases of thegeni t o- urinary system Diseases of the skin and cellular tis- 1 2 2 1 . 17 .17 .23 3 3 .70 .70 4.28 .67 2.29 1 lisea ses of the or- gans of loco- 1.08 .17 1 suits of 1 .0002 35 9 16 .9.5 .25 1 .01 1 .01 .11 Total f'»r diseases. 2,012 392 526. 13 102.56 46 5 10.74 1.17 15 3 50 .70 98.50 25 77 17.20 4.50 04,354 14,646 S65.92 197.07 1.110 121 15.20 1.61 228 142 3.02 1 . 88 2,647. 19 135.61 35.62 5.86 Total for diseases and external 2. mi 628.99 51 11.91 18 t.20 115.70 30.27 79,000 1.062.99 1.270 16.84 370 1.91 3,083.10 41. 4S For the U. S. army the accompanying charts (see pp. 505 and 506) so well illustrate the remarkable decrease in sickness and death which has occurred during the past three-score years that any extended discussion of the matter would seem to be super- fluous. Suffice it to say that the death rate for the five years preceding the Spanish-American war was about three and one-half times less than that for the five years preceding the war with Mexico, while the rate for sickness underwent a diminution of about two and one-third times during the period included by these dates. Since 1S72 the death rate from ail causes has dwindled to about forty per cent, of what it was at I hat time, while the death rate from sickness alone has fallen almost as much; and during the same period tin- rate for admissions to sick report has diminished more than one-half. In the German army, according to official figures recently submitted to the Reichstag, the number of 602 admissions to hospital from disease, per thousand strength, underwent a decrease from 1,496 in the year 1868 to 867 in 1894. In 1S6S the annual death rate per thousand was 6.9, 1.82 in 1S79, 3.24 in 1888, and only 2.60 in 1896 — a magnificent result, in the attainment of which the due observance of sanitary detail, and especially the careful selection of recruits, were main factors. .Military epidemics, in thia showing of the German army, have above all lost ground. Smallpox is rare, and caused only two deaths during the twenty year.-. 1S73-1S93. Dysen- tery was reduced from 6.S per thousand strength in 1S74 to 0.39 in 1894. Typhoid fever gave a rate of sickness of 33.8 per thousand strength in 1868 and 2.4 per thousand in 1894. The typhoid death tale was 2.2 per thousand in 186S and' 0.S1 per thousand in is'U. Malaria showed a rate of sickness of 27.fi in 1868and o.sl per thousand in 189 1 : while contagious eye inflammations fell from 7.0 to 1.5 per thousand. REFERENCE HANDBOOK OF THE MF.DK'AL SCIENCES Army Medical statistics 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 1 .1 8 8 11 13 16 18 21 23 26 28 31 33 36 38 1 A 1 ffl 48 i ' B 1 OS ■ n SB 71 7S 76 78 2 4 7 12 14 17 19 22 24 27 20 32 34 37 39 42 44 47 40 B2 -.4 '.7 _fl 62 64 67 E'. 72 74 77 79 1840 1840 1841 1842 1843 1844 1845 r L -LL^ 1845 1846 1846 _*7! |WAR W TH MEXICO- YEAR OF CHOLERA EPIDEMIC 1850 1851 1856 - --■__- 1857 r -■ 1858 ----- ,- 186 c, \. c V,L WAR loee AN ^PIDEvl'lC OFr SMALL-POX DURING THIS (■EAR FuWhsWeC 877 DEAT HS'. iQfifi iofi7 A^l :p PEVllC OF ]ch6_.Er|a [FURNISHED hlsiC ' deAths. 1 | — -tTT 1867 iqco lEPICEMIG OF CHOLERa]anD YELLOW _EEY-Ef -FURNISHED 6G1 DEATHS oc _ 1871 — L- I __ — _L 1 1070 _u __L _i__ _' _J _ ! 1ft7 o !___/ \__ I 1 18/(3 / ^< 1074 _L J_ ' ^£L _ _ -_- 18/4 I875 ---I L^_L_' io^ Y£ AR ^FvcJsTER^m'a^SACRE WHEN 2^7 Mb WE1E KILLED 1876 1879 - -- 1881 1886 ^ \ _____________ 1887 ---{ 1888 )r- ■ - -- -- ----- 1889 -{-£ -- 1895 {--- -- -- -- -- 1896 j-J.____.--__ - - - __ -. 1897 L-L - _ War with spain 1898 603 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ^ CM en _u _. 1 GO d r- , , , 1 LfJ _ . - .. to ~ -— : ; : - - . . ... in — - - ~ :i: : — ■-- -- --- Tf .11. . O !__ . x — - " ; z : — :::~~: CJ _ ...... en _ ----- CO _: : : zzzz .. . t- 1 X ' ■ <£> . . . .J. . • :::|: m | d - — — - -"'... f--:--- it : Mil! > o . d . .... . . ^_ : _. . . ^ ^ ^ ~~ i - t *- ...... r.- i o z a 1- (0 u -1 U. O fe o x O y u. £ °! £ UJ •" g z 5 a -III L___ _■_ ' ' 1 1 i 'EAR. 64U. 841 . 142. ID » ID » N t -* tf tf - ISC'- "J *o -t - - ,- i.o in in » S » B K B * ifi b n a oi o •■ is ji ifi in K THK MKDICAL SCIENCES \r m\ Medical Statistics A. — Ratios of Admission to Sick Report, Discharge;, Death, and Constantly Non-Effective of the United States Army for the Decade L886 '..r the I I88fi Whii Colored. Indian. eta strength.. A. G ,24,301 S. G., 22.071 A G ,2,379 S. G.. 2,188 A G , 227. S. G.. 213 J 1,172 of admis- .. k report . Lnia ...id fever. M :il:uial infect ions Tuberculosis of the lui ' - - irrhea \ll venerea) dis- housm and direct results. Jgia Hitis Colic and consti- pation Diarrheal dis- eases Diseases of the heart -■: ...... lir tnchitis Pneumonia ases of the kidneys. . . Rheuniaiism and myalgia Boils and ab- Conjunctivitis AH diseases of the All diseases of the ear Contusions and sprains Dislocations Fractures. not gunshot Wounds, not gun- shot Wounds, gunshot. Grouped. Infectious dis- general cal nutri- tion, general. . Di -eases of the nervous I 'i lases of the digestive sys- if the circula! ory :i . if the respirat ory - . Diseases of the -urinary m if the lymphatic sys- tem and ductless glands. 33.76 0.004 5.94 .01 96 _' i .09 5.11 .07 1 52 17. IS 1.98 . 26 2.30 42.37 .07 24 69 .16 41.37) .001 32.10 .02 0.61 .1 I .02 1.06 .91 .59 ; = & 1 .44 .70 .01' 1.6S - .02 5.26 .47 .62 26 .21 2.10 0.50 64.50 0.04 .38 5.76 .04 3.93 1.85 .84 .in :>2.ll .ii! 7s. is 3.40 .04 5.21 II 76 1 71 "7 7 02 115. 6S 5 . 79 ; 56 67 . 9 1 1.72 7 ; 28 43 7 1 11.86 17.95 7.67 130.04 2 . 7.7 50.21 3.30 . 22 1.36 .01 .13 .42 .23 .06 .20 1.59 .02 .06 .9S .54 .02 .66 .23 .02 .004 .29 1.34 .53 .29 1 37 .41 .21 3.65 99 .32 .78 .34 4. Ml 49.18 99.75 4.94 41.36 69.26 6.90 2 - . 116.33 2 26.51 14.49 26.71 1 3 . 70 .01 .04 .17 .13 18 25 .17 .os 1.7,1 29 .34 02 ... .04 .21 .23 .11 .01 .004 3.33 .20 .52 .10 1.20 .2'! .64 .05 .96 1 1- .57 145.86 1.S7 6S.07 : : 302.66 4.15 2.55 .59 96.67 3.12 278 10 . . • 1.73 .09 .7 ' 13.18 276.73 2.10 2. 12 7.14 1.71 .05 4.40 .51 .69 77.07 300.59 .34 ill .OS .08 Ml I. (ill . II 1.14 .30 .30 1.20 .60 .22 4.56 .67 . 15 1.04 .16 3.36 .11 1.99 .•17 5.76 2.14 .04 . 16 .IS 5.30 ! 1.26 .50 .47 2 ■ 4 . 2:; - 1 5 . 5 1 2 98 26 2 4 . 70 15.05 31 .50 45.01 2 . 35 12.09 in 34 5il 7s 1 42.:>l 44.67 62.06 S.46 128 82 6.11 1 1 . 75 91.20 7.05 II 7 64 64 :;j SS 4 in 9 BE d >- a 1 lischa a a - ~. - 3i 4.14 .iij .47 .58 3.55 I .76 :;.17 r. . 77 ,ii7 .17 .41 .34 .16 .11 .82 .711 0.004 1.06 84 .16 2.40 5.16 .117 .02 58 3.21 1.63 17 75 2.11 !8.6 J I 76 12 2.40 1.54 1.21 1.21 25.70 42. 12 33.62 113.65 5.69 34.08 67.97 4.20 1.S0 76.94 .07 .11 .004 .02 .21 1.34 .54 .75 .02 1.71 J J I . 1 12 5 . 26 .20 .01 .22 .06 .20 1.63 .16 3.02 .52 42.18 12 - 19.13 7.32 .02 .07 .99 .50 .13 .41 .112 .74 .24 .02 .004 re i . 52 2.10 1.05 84 131.46 .23 .01 2.54 .11 .004 6.S6 .50 .11 52.16 .20 .05 3.69 .66 1.05 .43 .62 .66 .30 1.32 .51 .29 1.35 .43 .21 3.71 .97 .34 .82 .33 3.33 .20 1.7:! .61 2.40 11.55 350.26 15.41 7.04 17.45 300.76 4.39 1.84 13.09 1.41 1 57 41. 3S 7 IS 4. us 180.54 2.35 1.32 .Ii .us 2 . 57 .lii -- . !■ 2.7.0 .56 94 . 4 1 3.02 .7", 113.1 ! .58 .78 2.49 130.55 .341.81 2.7.7 92.15 1.32 .8S 2.46 11.33 .SI .24 .85 14.49 .97 .31 .93 7. 99 .11 . .21 5.35 .07 .004 .44 6.95 11.28 .'i : .09 .22 .76 2.24 .62 4.35 6.93 1.66 .51 .66 111.;' .7,1'. .s7 2.50 11.58 .82 .25 .S5 5.54 .06 .004 .45 (a) For 1SS7-95 — nine years of decade; (fe) for 1891-95 — four years of decade. 605 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES -Ratios of Admission to Sick Report, Discharge, Death, and Constantly Non-Effective of the ■ United States Army for the Decade 1SS6-95. — Continued. For the Decade 1886-95. Menu strength. 1 Luses of admis- sion to sick report. White. i 'oli.n.-il. Indian. A. G., 24,301. S. G., 22,071 A. G., 2,370. S. G , 2,188 ? 8 ^ IB a oj >> > 'tn cc 1 B 1 DQ 8 T3 >.£ Total. A. G., 26,907. S. G., 24,472 I B Is 8! Diseases of the muscles, bones, and joints Diseases of the integument and subcu- taneous con- nective tissue. . Diseases of the organs of spe- cial sense Unclassified I leneral injuries. . Injuries to special parts Total for dis- eases Total for in- juries Total for all causes 79.16 ;.07 .01 79.47 .23 27 . 53 2.79 3. 25 245.13 1.65 !o2 .01 .004 1.02 1,005.77 24S . 38 1,254.15 3 . 36 1 . 26 16.34 3.39 1.S4 2.2S 19.72 7.12 3.74 1.27 .07 .08 8. 17 121.-11 31.45 5.21 1.87 2S9.26 3.24 1.39 .111 3. 15 .01 .42 1.08 :i so 8 . 5 1 40.31 1,022.31 291.13 1,313.43 16. 4S 6.05 I 3.49 2.40 19.97 8.45 1.89 1.26 .08 .04 9.35 29.53 9.39 53.60 71.93 72.40 2 . 82 302.30 888.11 302 . 30 3S.92 1,190.41 2.64 21.57 2.61 24.21 . II . I 1 6.60 1.3S 2.19 2.19 ..01 9.76 S2.7H 76.81 28.27 3.00 3.10 249 . 57 2.71 .01 .23 1.62 .03 3.36 9 . 76 1,006.22 252.67 16.39 3.39 16.72 40.03 1,2S8.S9 19. 7S .02 2.06 .01 .304 .'.ill 1.37 4.99 2.33 7.32 1.28 117 .07 8.S7 ,i 62 40.26 (a) For 1SS7-95 — nine years of decade; (6) for 1S91-95 — four years of decade. Decrease of Rates for the German Army. Year. Morbidity per 1,000. Mortality per 1,000. Invalided per 1,000. 1879-80 1.174.8 1,136.2 1,135.5 S49.6 S30.1 S50.3 S49.2 808.0 S04.1 758.9 S97.2 4.S2 1 . 82 4 . 53 4.25 1 16 3 . 93 3 . 73 3.79 3 . 2 I 3.19 3.30 1880-S1 .. 18S1-82... 1882 S3 20 6 1883 84 20 7 l.ssi 95 20 4 1885 86 23 'i lSSli 7 20 6 1887-88... 21 5 188S-89... 19 6 1889-90 25.9 According to Boisseau the mortality of the British army on the home station prior to 1853 was 17.5 per thousand strength. After the improvement in the sanitary surroundings of the soldier in that service following the Crimean war, the rates for death and sickness were much diminished, and for the decade 1875-1884 had fallen to 7.20 deaths per thousand strength. In 1889 the death rate was 4.57, the sick- ness 730.4. In 1S90 the deaths rose to 5.53 and the sick rate to 810. For the decade 1887-1896 the admissions were 735.9 and the ratio of deaths per thousand strength was 4.68. In 1897 there died only 3.42 per thousand of strength, while the admission rate had fallen to 640. per thousand strength. The reduction in the rates for sickness and death in the Italian army during the past twenty-five years has been steadily progressive and probably presents less fluctuation than is the case in any other military service. G0C Admissions r> e . 1 (h Admissions to hospital rat Year to hospital or infirmary , n0( . or infirmary per 1,000. ' I per 1,000. Death rate per I .nun IS 75 1,031 13.3 1887 760 S.7 1876 1,001 11.2 1SSS 732 8.7 1877 987 10.6 1SS9 7 19 8.0 1878 '.117 10.6 1890 796 7 .7 1879 936 9.9 1S91 811 9.0 1NSO 935 11.0 1S92 758 7.1 1881 928 10.6 1S93 735 e a 1SS2 833 10.2 1894 723 5 2 1883 842 11.8 1S95 713 7.0 1884 779 11.6 1896 711 5.8 18S5 791 10.3 1897 694 4.2 1886 798 9.3 Viry gives the following rates for mortality in the French army as illustrating the progress of military hygiene: Period. Mortality por -. . . 1,000 strength Pennd ' Mortality per 1,000 strength. 1812 27.9 1873-81.. 9.0 1820- 25 1846 21.4 19 16 13 1SS3 ' 8.15 1S89 1846-58 1862-72 1S90 5.81 Dewey states that in the French service the average annual death rate was 8.43 per thousand strength for the seven years 1880-1886, and that it sank yearly average of 6.63 for the seven succeeding years. REFERENCE HANDBOOK OF TIIF. MKDK'AL SCIENCES Army Medical Statistics his decreased death rate is naturally consequenl to . d amount of sickness, as the following figures r om Marvaud illustrate: Period. L862 L86 L866 1884 1869 1887. Amissions t.) hospital per thousand strength dons to infirmaries and cases treated lers not included) 264.5J259.5 177.0 ani ni in-effei I i i es pi r thousand 1 2:;.:; 22.1 14.0 Lindley, writing in 1S92, states that during the ng forty years the death rates in the Prussian n,l Belgian armies had shrunk to two-fifths, the inglish ami Russian rates had fallen to one-half, and he French rate had diminished to one-third. These igures may probably be accepted as being approxi- uately correct. The lamentable conditions revealed by the above s as existing until even within the present generation were undoubtedly largely due to ignorance if first causes of disease, by which measures for its ion could not be intelligently applied, as well is to an insufficient knowledge of hygiene and lack of appreciation as to its value from a military stand- >oint. An additional factor of no mean importance, towever, was to be found in the former anomalous .ml inferior condition of the medical officer, his lack if authority to recommend in sanitary matters, and lis powerlessness to control or remedy existing eondi- ions. It was long held that his duties were merely ,< rare for the sick and wounded, and any recom- nendations bearing on the general care or manage- uent of the men were deemed intrusive and as such usually disregarded and resented. The compara- ivelv recent conferring of advisory powers upon the mrgeon lor sanitary purposes has undoubtedly been i potent factor in the gradual betterment of the ;anitary condition, and hence efficiency, of the loldier; and when the medical officer is invested .vith actual authority upon all matters bearing upon be health of troops, with executive powers as well as I Ivisory privileges, a still further improvement in his direction may be expected. Although during the past one or two generations a narked diminution has occurred in the sickness, nortality, and non-efficiency among the troops of the States and those of European nations upon !ii home stations, the same unfortunately cannot be :ii 1 with regard to white troops doing colonial duty II tropical climates. For them these rates continue be high, and no great improvement in their relative sanitary state, as evidenced by statistics, appears to have resulted for many years. Since the hygienic requirements for each military establishment, wher- 3 troops may be stationed, must be accepted 1- being the same for all circumstances, the conclusion is obvious that climatic conditions in the tropics furnish :i potent obstacle against a constant reduction in rates proportionate to those which have occurred on the home stations. While undoubtcdl}- much lias lone during the past generation to render military service in hot countries less inimical to life and health, the fact none the less remains that sani- i.'.ry progress in the low latitudes has fallen far short of that obtaining in more temperate climates. It is that figures illustrating this point are best furnished by the records of the British service, and are briefly compared as follows: a these figures it is evident that while there was a considerable diminution in the morbidity and mor- tality rates for the West Indies and Ceylon during the past twenty years, but little improvement has oc- curred in the general rates fur China, Egypt, and Cyprus. In India, a country long occupied b large military force and one in which the grea improvement might reasonably be expected to have occurred, the rate: are practically what they wi decades before -the death rate of British troo] home having fallen from 7.20 to 3.58 per thou while the same rate for India fell only from 17.43 t" 15.29 during the same period. Further, the several rates f"i' the Straits Settlements have actually in- creased. 1 leatht 1 lays Period. hospital |„T per 1,000. 1,111m. Decade 1S75-S4. 885.0 Decade 1886-95. 111.",. 7 '.1 23 22 67 Year 1S96 1190.2 6.19 28 69 Decade 1875-84. ins;,. 1 14.51 2U.II7 Decade 1S86-95. 1004.1 11 ,38 21 . 10 Year 1896 . 1321 .1 8 . 23 2:; . 711 China Decade L87 Decade 1SS6-95. 1030.4 1256.0 10.53 11 .41 18.07 22 . 1 1 Y'ear 1S96 1856 5 7.48 32.05 India Decade 1875 8 1 . 1 182.9 17.43 23 . 06 Decade 1886-95. 1 153.5 15.52 30.26 Year 1896 1386.7 1 5 . 211 34.35 Egypt and Cyprus.. Decade 1S75 8 1 No fig ures gi ven. Decade 18S6-95. 1069.7 16.30 24 . 56 Year 1896. 822.3 1 3 . 28 23.11 Straits Settlements. Decade 1875 S 1 X" fig are- iri ven. Decade 18S6-95. 1079.4 7.27 25.58 Y'ear 1896 11171.7 8.88 26.46 In this respect the experience of Great Britain is duplicated by that of the French service; in which in 1862 the mortality for troops throughout France was 9.42 and for those in Algeria 12.21 per thousand; while in 1890 the death rate for troops at home was 5.81 and for those in Algeria 11.94 per thousand. TFor as Affectimj the Health of Armies. — The rates of sickness and death of troops in campaign, inde- pendently of the circumstances which accompany conflict, are chiefly influenced by the standard of hygiene maintained; and, as is stated elsewhere, it is difficult to cite campaigns in which the death rate from sickness has not been greater than that from casual ty. The diseases observed during continued warfare, according to Laveran, are largely brought about by four chief influences: atmospheric, exhalations from the soil, evil condition of the latrines, and poor food. The atmospheric exposure to which the soldier is often subjected is one of the greatest hardships of a cam- paign. Sleeping on the bare ground and often drenched with rain, standing in trenches exposed to snow and cold, or making long marches under a tropical sun, are a few of the influences by which he is debilitated and his constitution impaired. Service in a malarious country is notoriously productive of disease, while illy-policed sinks are potent factors in the occurrence of typhoid and dysentery. The influence of insufficient or improper food in lowering the resisting powers of the soldier is well recognized. Excessive fatigue and moral influences also play an important part in determining the sick rate, it being well established that victorious forces have less sick- ness than armies which have been beaten and demoral- ized. The endemic and epidemic diseases of an occupied country, together with the influence of a change of climate, aggravate also to a considerable degree the sickness and mortality of an expeditionary corps. For our own service the influence of hostilities upon 607 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES GO to ir == ^^= in -t - ^=^ T— CO PJ i— O 03 = ee^ee: ||111| ^EEEE ^nm c 0) -o CO to m == — ^^= 10 *t <* CO 03 . ■ ' F - - ~: ! 1 J— i g ■■ ' fl 1 ' 1 n n z •■- r/J .j I H cr Q. <0 I. J < Q to DC U > UJ U_ D U z h z o (J ay CC UJ > UJ U. _J < < < 5 Q < 2 o = SI O C J J f> 3 CO cc UJ > UJ u_ UJ > Q. z> cc UJ to -? Eg u. ° o > < < UJ cc to a. Q CO UJ tr Us? O to CO to U 3 to o ^ > UJ a: to u a z to wl 1- CE o> EC to Q uj y to ^ o tr o UJ M to ul UJ > UJ qJ « a Q 5 z o Q. S Z> to z o o 5 to 1- < s =3 UJ I tr > > tr o to Eg < & ■ s ffl ■* o E ^ 2 a -a £ o c a | & 3 3 6 & ■s « 'C - ~ 01 S g J o is :* ■r to s i a a — 608 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Army Medical Statistics mortality from disease is well illustrated in the accom- panying chart (p. 608), showing, as it di>e>, the rates [or certain affections in the United States army, dur- M! r the Civil war, for periods before and subsequent Othat war, and also as compared with the death rates or the corresponding class in civil life. As compared with the mortality from continued fevers — which ins may he considered, in the light of present aowledge, as of typhoid natun — war brought about in increase of tenfold. Malarial diseases were 1 and diarrhea and dysentery tripled. Deaths mm eruptive fevers became about twenty-two times is frequent as they were before the war, while those rotn diseases of the respiratory organs were more [uadrupled. Camp life appeared to have little nlluenco in affecting the mortality from nervous ons. Deaths from diseases of the circulatory nl digestive organs were practically doubled in fre- quency, as was also the mortality from consumption. Rheumatism, as regards a fatal termination, and con- iaiy to expectation, was not increased; but scurvy — be former bane of armies in the field — was doubled. The average annual death rate from disease during the entire war was 53.48 per thousand strength imong white troops, while it was 18.98 for these during the eighteen years before the war, xcluding the two years of hostilities against Mexico, and somewhat over six per thousand for the decade [uent to the war. The following table shows the influence of the war with Spain upon the rates for sickness and death, as regards the prevalence of certain classes of diseases: UNITED STATES TROOPS I YEAR 1881-2 \ FROM TYPHOID FEVER MORTALITY - 1 FROM DISEASE 1 YEAR 1898-B FROM TYPHOID FEVER f4 < MAY IJUNC JULY AUO.|»EPT, OCT. NOV. | OCO. JA* ffl>,|M»H '*>n JJ.O. 5.5, _5.0 I 5 0.0 0.5 5.CL A / \ \ \ 1.5 4.0- 3.5- 3 0- \ \ 1 '1 \ j \ \ .3 5- i • 30L _2.5_ i : ':/ \ 2.5. -2.0- 1/ A \ s 20 1.5 1.0- !/ :< \ \ / 1.5 1 y \ \ — 0.5- 1 ; • '"■■*" ~~- 05 -0.0- •""" .-/ ' Fig. 326. — Mortality from All Diseases and from Typhoid Fever during the War with Spain and during the Corresponding Period of the Civil War. (After Sternberg.) Table Giving Figures for the Comparison or the Year of Peace, 1897, with the Year of War, 1S9S. Group. Admissions per 1,000 strength. I lonstantly non- effective per 1,000 strength. Deaths for 1,000 strength. Discharges for disability per 1,000 strength. 1S97. isi.s IS',17 1S9S. 1898. 1897. Total losses per 1 ,000 strength. 1897. 1S98. Infectious diseases, general and local Diseases of nutrition of the nervous system Diseases of the digestive system ■ nf the circulatory system Diseases of the respiratory system - of the genitourinary system Diseases of the lymphatic system and ductless glands Diseases of the muscles, bones, and joints, of the integument and subcu- ius connective tissues i of the organs of special sense... . [tied total for diseases Total for injuries Total for all causes 326.10 2.05 56.94 244.05 4. OS 77.71 9.76 2.36 72 . .32 72 . 55 21. 17 2.41 1,034.97 3.49 52.81 505.71 6.73 114.511 11.77 3.22 77.34 60.57 17.39 19.17 S96.53 l.'i::7 71 290.08 209.23 1.1S6.61 2,146.94 12.59 .19 1.63 3.75 .41 1.61 .SO .17 2.85 1.70 .92 .09 26.73 9.12 35.85 57.90 .21 1.33 7. CI .60 2.04 .67 .17 2.70 1.06 .79 .59 69.09 1.35 .33 .55 .37 .04 .04 .04 3.14 1.97 5.11 15 '.19 .09 .92 3.11 .49 .96 .24 .30 24.94 8.41 33.35 1.28 .29 1.79 .55 .95 .40 .44 .31 7.60 2.01 9.61 2.14 .13 .86 58 .96 .26 .43 .02 1.33 .04 .62 .02 7.40 4.1.8 11.58 2.63 .29 2. 12 1.10 1 . 32 .62 .66 .01 1.31 .62 .04 10.74 18.13 .22 1.78 3.69 1 . 15 1.22 .67 .02 1.33 .34 .62 .02 32.34 44.93 All things being considered, it is safe to assume that I outbreak of hostilities will be followed by a vast increase in the death rate, probably from six to twelve or more times that normally occurring in peace; the proportion naturally varying with the character of the campaign, the climatic conditions to be encountered, the local diseases to be undergone, the efficiency of the commissary and transportation departments, the employment of seasoned or unseasoned troops, and many other factors. The rate of admissions to sick report from disease in time of war is not, however, increased proportionately to the death rate — a fact .sufficiently proving the more serious nature of dis- Vol. I.— 39 eases when affecting troops in the field. As to the rate for non-efficiency, this is largely dependent upon the ratio for admissions, and naturally bears in its fluctuations a close relationship to the prevalence and character of disease. If the records of the Spanish- American war be accepted as typical in this respect, no great differences in the rates for discharge by reason of disability, in peace or war, may be antici- pated. (See chart, above.) In comparing the results of the Spanish-American war with the corresponding period of the civil war the advantage is much in favor of the former, al- though the progress of disease by months is quite 609 Army Medical Statistics dissimilar. It is particularly noticeable that not only was the death rate during the war with Spain reduced by 43.9 per cent, as compared with the struggle of the previous generation, but the amount of epidemic typhoid, largely resulting from the inexperience of the volunteer troops, rapidly decreased as a result of scientific sanitary measures enforced as soon as the magnitude of the typhoid outbreak was fully understood. And in future wars, through pre- ventive inoculation and better appreciation of the protective value of good sanitation, the amount of typhoid fever to be expected will be very greatly reduced below past standards. Comparison of Monthly Death Rates (per 1,000) from Disease. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES 1S61-1862. 189S-1S99. Months. 5 M l_ 50 o ogaj a » a a 3 >-i S iS s 3T3 *-8 K |^ « i~° 16,161 r.6,'.i.-.i> 71,125 112,359 IS 55 106 242 1.11 .82 1.49 2.15 (i 1 5 .26 .44 .72 .21 42 90 451 1,400 163.726 _' 12,526 July 362,613 August 268,507 September. . . . 165,126 365 2.21 5 .89 1,541 261 ,824 October 256.SS4 725 2.S2 :; .IV 809 _'.-,.-,, Ml III November. . . . .301,848 1,145 3.79 1 .51 365 242,000 December 343,184 1,471 4 . 29 .84 201 240,000 January 352,760 1,593 4 . 52 .85 ISO 211. 327,734 1,316 4.11 .87 156 iso.ooo 328,S7S 1,575 4.79 .90 123 l.;r. ni III 410,116 229,452 l.SSl 10,522 4.. 58 45.86 25 .71 .73 SO 5,438 113,000 Annual 211,350 As already intimated, so many factors combine to determine mortality from sickness in campaign that any attempt at the close comparison in this respect of different wars — carried on under entirely different conditions — can yield only misleading results. Gen- eral deductions can of course be drawn, and hence the following figures may be of advantage as well as interest : Deaths from Disease During Certain Wars of the Past Century, i After Bradford.) Name of War. Nation. Mortality from disease per or period, i , 00 strength. Year Walcheren expedition.. West Coast of Africa. . Mexican Crimean Chinese Civil War Civil War Franco-Prussian Cape Coast . . Afghanistan Egypt Soudan Madagascar Chino-Japam-.' Spanish-American Great Britain.. Great Britain.. United States. Great Britain.. France United States. United States. Germany Great Britain.. Great Britain Great Britain.. France France Japan United States 1S09 1824 1S46-4S 1S54 1S62 1862 1863 1S70-71 1S73 187S-S0 1SS2 1SS3-86 1S95 1895 lS'.lS 346.9 690.0 100.0 230.0 118.0 40.0 60.0 IS. 6 173.0 93.7 72.1 2S0.0 i i il 14.8 25.0 shown in the following diagram from the report of the Surgeon General for 1910. Since 1897, the chart illustrates the influence on our medical statistics of the Spanish War; the Philippine Insurrection; the China Relief Expedition; various other outbreaks; the second intervention in Cuba; the opening up of new posts in Alaska, along the seaboard and in the interior of the United States, and in Hawaii; the occupancy of vast tropical territory and the shifting of troops therein, and many other factors. It will be noted that despite the far less favorable environment that surrounded our army at the time of the outbreak of the Spanish war, the death rate from disease is now about what it was then. For this, an improved sanitary administration is responsible. The rates for discharge and constant inefficiency still continue high, but these are largely the result of exposure to tropical infections together with the tremendous increase in venereal disease which has been the special sanitary feature of the past decade. The results of the Russo-Japanese war are not given here, as the statistics winch have been published are not regarded as reliable. The results of war, supplemented by the maintenance of troops under unaccustomed climatic conditions, and frequently in an unhealthf ul environment, are well G10 Pao.-ths Chart Showing Ratios of Deaths, Discharges, and Non-efficiency in the U. S. Arm} . With regard to the results of campaigning undci tropical conditions, the most satisfactory data are naturally furnished by the two great colonizing powers, Great Britain and France. The figures given for these services are, however, so widely dis- similar as to furnish no foundation for any general conclusions based upon them both. For pur) of comparison merely, they are certainly valuable; the French having little reason to be proud of their sanitary showing. REFERENCE HANDBOOK OF TIIK MKDICAL SCIENCES Army Medical Statistic! ABU OF MORTALITY PROM DISEASE IN CAMPAIGNS IN TROPICAL Coi .urn-, Showing Rati: op Death pbh 1,000 Strength. (After Bradford.) Briiish Expeditions. French Expeditions. oudan land lukim ludan I ih, n- ahanti '.II orce land, . kshaoti tiiuland hitraJ ... ,'ile loogola Lfuhaaistan . . 1889 I s7ii INS.", lss:, 86 1860 189 i 96 1882 is.;,- nn 1877-78 I860 1896 1S7I 1S7'.> ISM.", 0.6 2 n 1.1 5 5 5 12 14 14 16 17.4 24.8 25 . 1 1SS4-S.-. 26. I 1896 16.6 1878-8093.7 Tonkin 1884 Tunis 1881 I,. 83 Tim kin 1 ss:, 1 tahomey. . . . [893 Tonkin L886 Tonkin . |ss7 ( i>. Inn-China 1863 Soudan i lochin-China 1862 1862 Tonkin lsss lss.-, -si; Soudan 1SS6-87 Soudan 1887 ss Soudan 18S8-89 Madagascar. . 1S95 I ',11 II (il .11 71.0 79.0 S7.ll 99.0 I in; ii 107.0 116.0 117.0 118.0 133.0 200.0 220.0 225.0 280.0 HOO.O i i unities of the French expedition in Madagascar is given by Gayet: Killed by the, enemy 7 Wounded 04 Deaths from sickness 5,600 Sick, more than 15,000, or S3 per cent, of the whole. From the above table it will be observed that with lie exception of the Afghanistan campaign, in which he high mortality was largely the result of an out- ireak of cholera, the most unhealthful of seventeen English expeditions in warm climates had a lower 1 :ath rate than the healthiest of an equal number of pi inn campaigns under presumably similar climatic conditions. The British expedition against the \diantis, in 1874, certainly demonstrated the effi- •iency of military hygiene under notoriously unhealth- ul conditions; and, in the excellent results obtained, he second expedition against this same tribe, in 1896, even surpassed the first. In our own expedi- ion against Manila, during the war with Spain, the ■esults were admirable, only eight per thousand lying from disease. During the Cuban insurrection lie Spanish are reported, for the year 1S07, to have tad a death rate of thirty-six per thousand from all auses. The admissions to hospital for the same icriod were 1,900 per thousand, of which 420 per housand were for malaria. During 1897 the Spanish roops appeared to have suffered but little from yellow ever; this being probably due to an immunity to this iisease acquired through previous visitations. That constant exposure to infectious disease of all kinds, and not only yellow fever, does actually exert a seasoning influence on the survivors and reduce their mortality is well known. As illustrating this point, it may be noted that the sick rate of colored troops during the civil war fell from 4,092 per thousand during the first year of their service to 2,797 in the last, while their death rate dropped from 211 to 94 per thousand strength. The total rates for sickness during the civil war underwent considerable diminution, as follows: First year, admissions per 1,000 strength 2,983 ~ ■ n,l year, admissions per 1,000 strength 2,696 Third year, admissions per 1,000 strength 2,210 In this connection the chart already given in the section showing the influence of race as affecting the prevalence of disease is of interest. It is not, however, dining active wars or on ex- peditions that the highest mortality is observed a moiig troops in tin- field. When an army is condemn- ed to inaction through a siege, for purposes of mobilization, or even in cantonments after a faborious expedition, sickness rages with the greatest violence. The typhus i bat nied tin- Crimean army occurred in the winter after the capture of Sebastopol and aftt c conclusion of the armistice; and examples might be indefinitely multiplied in our own service to show that the stationary force, dining war, is an un- healthy force. In January, lsi>2, the medical director of the Army of the West, then in winter quarters, reported 13.5 per cent, of the total strength as bring excused from duty, and a little over twelve per cent, in March of the same year. [n August, 1861, of some troops encamped on the Arlington flats on the Potomac, thirty-three per cent, were reported sick with diarrhea and malarial fever. During the war with Spain the typhoid epidemics, as is veil known, occurred in the large fixed camps. An ex- cellent instance is found in the condition of the French troops during the Crimean War, a struggle from which so many sanitary lessons have been drawn. According to Rawlinson, reliable estimates as to the sickness among these troops, for the winter ■ if I 854—55, were as follows: 46,000 55,000 6.->,000 75,000 ss.000 3,200 .5,000 December January February. . 6,000 9,000 S.000 These figures do not include the sick treated in the regimental infirmaries or in the hospitals at Constanti- nople. Comparison of Military Statistics. — It is a matter of the greatest difficulty, if not indeed impossible, accurately to compare the sanitary conditions of various armies, since their statistical tables are often differently constructed, the physical requirements for recruits are not identical, and diverse regulations as to discharges for disability prevail. In attempting to institute such comparisons it is well to appreciate at the outset that a sick rate can be kept low by excluding the doubtful or milder cases from the benefits of quarters or hospital, and so pre- venting them from appearing on the official records; that the sick rates, mortality, and constant non- efficiency can be held down by a searching system of discharge for disability, and that the total loss — as shown by the sum of the rates for death and discharge — is, in determining the sanitary states of an army, of much more importance than either of its com- plementary factors. In comparing the rates of our service with those of foreign armies the admission rate is the one which, by its magnitude, attracts attention. This higher rate of admission, however, does not in itself imply a greater prevalence of disease among the troops of the United States; since with us, in contradiction to the practice in other armies, the soldier is officially taken on sick report whenever he is excused by the medical officer from any part of his duty, whatever be the cause. When it is observed, as was the case in the year 188S, that 796. .89 admissions per thousand strength from the Italian army resulted in a death rate of 9.31, while 1,270.73 admissions for each thousand United States troops for the same period — divided into 62J.61 611 Army Medical Statistics REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cases admitted into hospital and 649.12 treated in quarters — had a mortality of only 8.15 per thousand, it is evident that the admissions in the two instances — the rates for discharge for disability not varying greatly — do not constitute facts of equal gravity and are therefore not available for comparison. The rate for constant non-efficiency is obviously largely dependent upon the admission rate and that of discharge for disability, and reflects, to a con- siderable degree, their variations. Taken by itself the rate is misleading, and it acquires a certain value only when considered in connection with other rates, particularly that for admissions. As between services, for the reasons already given, it is evident that non- efficiency rates are not susceptible of proper com- parison. The death rate alone, as a means of comparison be- tween several armies, is wholly unreliable and merely productive of error; since, as above stated, it can be marked reduced by the removal from the service of those subject to or predisposed to disease. Of all the ratios which go to determine the health- fulness of any army, as shown by statistics, that giving the discharge for disability is of the greatest importance. In its relation to military morbidity it is at once evident that the admissions to hospital will be largely furnished by the physically less sound, and that a prompt and proportionate diminution in the sick rate must follow the elimination of these weak- lings by their discharge from the service. In addi- tion, the number of men withdrawn from the ag- gregate strength of the command, the rate of non- effectiveness from disease or inujry, is not a factor of equal importance in all armies and cannot be justly used for purposes of comparison. It undoubt- edly embodies the number of admissions and the gravity of the cases so admitted; but it is obvious tli at the constant non-efficiency as well as the ad- mission rate varies inversely with the rigor of the system of discharge. As to mortality, this too depends upon the physical standard maintained, and, as shown in the German army, a low death rate is naturally consequent to the early elimination of those soldiers who are predisposed to or actually affected with disease. Hence the rate of discharge for disability is the controlling factor in the determination of the rates of admissions, deaths, and constant non- efficiency; while it is itself largely dependent upon the physical standards to which the recruit, before en- listment, is required to conform. To institute ac- curate comparisons, therefore, a constant, unvarying standard for discharge for disability should obtain in several military forces to be compared; and such a constant standard does not — and practically cannot — exist. Requirements as to discharge for disability necessarily vary with the customs of each military service, and, to a certain degree, with the personal equation of each medical officer. As an instance of the former, it may be noted that the Germans are especially assiduous in promptly removing the tuberculous from their armies; we, on the other hand, maintaining a sanitarium for soldiers affected with this disease; and this single source of error, to which might be added many other less aggravated instances, prevents a comparison of sick rate, mortality, and non-efficiency upon anything like equal premises. If it be admitted, however, that the physical re- quirements for the recruits of various armies are approximately the same, the total losses, irrespective of either non-efficiency or admission rate, should afford a somewhat inaccurate, but still the most available and satisfactory method of determining the comparative health and physical efficiency of various services. The following figures, taken from Marvaud, show the annual sick rates, mortality, loss by discharge, and total losses in various European armies for a period about ten or twelve years ago: X.'IMic < o E o f ~ s a S3 S 3S Belgium Austria Great Britain (home stations) France (home stations) Germany Italy Russia Spain 1S87-S8 338* 3.9 17.0 1887 995t 6.9 15. Of 18S4-S5 877 5.2 20.0 1888 500 6.1 21.0 ink;: m 819 3.9 29.0 1887 760 8.7 28.0 1880-S4 845 8.9 31.3 1886 13.5 30.8 20.! 21.1 25.: 27. 32.! 36.; 40.: 44.: During the year 1SS8 the total admissions p< thousand strength in the United States army amounte to 1,270.73, the deaths were 8.1.5 per thousand, tl. constantly non-effectives were 41.91 per thousanc the discharges for disability 27.75 per thousanc These figures give a total annual loss of 35.90 — tin making our sanitary showing for that time inferior t that of the above-named nations except Italj Russia, and Spain; all countries notoriously the lea> advanced in matters pertaining to hygiene. It cai however, scarcely be believed that our men, undi equal conditions of selection, broke down nearl twice as readily as the Belgian or Austrian soldiei and half again as rapidly as the British soldiers, an hence the conclusion would seem to be inevitabl from the above figures that our troops were at th:i time examined on enlistment with a laxity as to thei physical condition which did not obtain in foreig services. This idea is further strengthened by th fact that during the same year (1SSS) out of 742 me discharged on certificates of disability, in 129 instance the disability was specifically declared to have e:i isted prior to enlistment. About this time the larp number of discharges for disability attracted th attention of the authorities, and recruiting officer were warned to be more strict in their examination for enlistment; while a general order required tha all men recommended for discharge on account o disability be sent to the headquarters of each militar; department for observation by the chief surgeoi pending final action in their cases. As a result > these requirements the rates for discharge weri decreased by nearly one-half in a single year, sine which even further diminution has taken place. Fo the year 1897 the rate for discharge on account c disability was only 9.61 per thousand as compare) with 27.75 during 1SS8. On comparing the statistic of the above armies for a more recent period — exclud ing France and Spain, for which countries no late figures are obtainable — the relative status of th< United States service is found to be as follows: Country. Admissions to hospital or infirmary per 1,000 strength. Death rate per 1,000 strength. I lischargeg for disability per 1,000 strength. r. ° b a, C - i c H o 1S95 1S97 1897 1897 1S97 1896 1897 819.0 129.3 1.1S6.61 640.6 694.0 31 1.6 332 . 7 2.6 2.0 5.11 3.42 1.2 5.40 4.0 9.0 12. 1 9.61 1 9 87 21.2 21.9 37.5 11 6 1 1 1 United States Great Britain (home 11.7: 11 B Italy * General hospitals only, t Including detention in barracks. % Not including temporary invalids. 612 REFERENCE EANDBOOK OF Till: MEDICAL Si T I Army Medical Statistics It is evident from the above that much had ba Q LCCOmplished during the next decade toward improv- es the sanitary condition and effectiveness of our irmy and it is safe to assume that at the present time he 'United States soldier is better card! for than is he man-at-arms of nearly every other military service. sanitary standing of our army, as com- iarea with that of other armies of the world, and rearing in mind that the climatic and other conditions which these various forces are serving are [tiite different, is quite well illustrated in the follow ins; ■hart from the report of the Surgeon General for 1910. Although, as stated, attempts at the comparison of tatistics of different armies are at best necessarily in- T)'l ScKo>.RqeS I I Scale io -to I iviek. accurate and unsatisfactory, within the limit - of the same service such action is both feasible and desirable; the standard for the health of an army, as expressed by Smart, being its own best annual record, i lutside of unusual vicissitudes, exposure, and epidemics, and of the unsanitary condition- which bri: [ and death into the ranks of a military command during campaign, the sanitary surroundings of the soldier t i i«mfcj '^ 'W'twm m nA ^^m III Fig. 328. — Series of Electrocardiagrams showing the Results Obtained by the Three Leads from a Normal Heart. (From Barker after Einthoven.) Of these lead II is most used and gives the biggest variations. A series of normal electrocardiagrams is shown in Fig. 328 and a key diagram in Fig. 329. P represents the auricular systole and Q, R, S. and T. are all dependent upon the ventricular systole. Any marked departure from the normal picture represents either some abnormality in the place of 618 1. Sinus arrhythmia. 2. Extra-systoles. 3. Auricular fibrillation. 4. Tachycardia. R 5. Heart block. G. Bradycardia. 7. Pulsus alternans. 8. Pulsus paradoxus 319. Q s -Diagram of the Electrocardiagram. (Hoffman.) Sinus arrhythmia includes those forms of irregu- larity in which each individual heart beat originates in the sinoaurieular node and spreads over the heart by the usual paths, but in which the intervals between the beats vary in duration. It is caused by variation in the strength of the impulses passing by the extrin- sic nerves to the heart and modifying its rate (chrono- tropic impulses). These impulses may pass by either the sympathetic (positive), or the vagus (negative), but the latter are the most important. Sinus arrhythmia is known by a number of different names each of which refers to some characteristic of one or other of the forms in which it is seen. Besides sinus arrhythmia, the following terms are in common use and are more or less synonymous: respiratory, diastolic, youthful, and vagus. Respiratory arrhythmia is applied to those cases in which the variations in rate correspond with (he phases of respiration. It would seem that where the medullary centers are in a certain condition of excitability, the rise and fall of activity in the re- spiratory center is able to communicate itself to the neighboring cardioinhibitory center, modifying peri- odically the inhibitory influence of the vagus. This is a normal phenomenon in the dog, in which animal the pulse is often more frequent during inspiration (Fig. 330). In man a similar condition may be induced by forced breathing. Diastolic arrhythmia is another synonym, and indicates the fact that this form of irregularity is due to variations in the length of the pause or diastole between the different heart beats, and not to any departure from the normal in the site of origin of the contraction wave or in its course over the heart, This is very well illustrated in Fig. 331, in which there is marked irregularity. In the venous pulse we can see the normal sequence of auricular, carotid, and ventricular waves in each cardiac cycle, but there is great variation in the length of the second onflow wave which represents the pause or diastole. The youthful type of arrhythmia is another term which has been applied to this form by Mackenzie, on account of the fact that it is more frequent in childhood. In the young the "pace maker of the heart" in the sinoaurieular node seems to be more amenable to vagus influences. A similar condition is present in convalescents when the heart is slowing down after the frequent rate of fever. It is also often seen in the neurasthenic and the debilitated. In all such cases sinus arrhythmia is common. REFEHKXCK HANDBOOK OF THE MEDICAL SCIENCES Arrhythmia, Cardiac Vagus arrhythmia is another name given to these , es, because it is usually through the vagus thai chronotropic influences responsible for the irrhythmia roach the heart. While the vagal effects ire "usually dependent on the alternating phases of espiration, this is not always the case. The activity if the vagus may be modified by a great, variety of nfluences reflex, central, and peripheral. It must ui he forgotten that even the endings of the vagus ii the heart may 1"' directly all'ecteil by certain drugs. \iiiung the conditions which have been thought to a causal relation to vagus arrhythmia are .lion, high intracranial pressure, brain tumor, neningitis, injuries and diseases of the upper cer- i spine, tumors pressing on the vagus, poisoning drugs of the digitalis group, gastric and other ■ I reflexes. found approximately equal in duration and loudm in succe ive cycles. Simultan i tracings from arteries and veins show waves of normal form and sequence, except in those parts of the tracings which correspond to diastole, which vary in length. The electrocardiagram is similarly of normal form except in the length of tin- pauses. Before expressing a final opinion the possibility of extra-sy toles, heart- block, and auricular fibrillation must be excluded. Prognosis. — Sinus arrhythmia usually tends to pontaneou ; reco\ erj , its I lie \ mil I, g] I1V , \ into I he adult or as eon\ale renee becomes complete. Treatment is unnecessary in most cases and where called for should be directed to the general health. Atropine often masks the symptom temporarily, but it is not necessary to give it except in those extreme cases of standstill of the heart. Car -J See I ~ J"9 J^ c Flo. 3".0. — Tracing from the Carotid Artery (above) and Jugular Vein (below) in a Dog showing Respiratory Arrhythmia. /, Inspi- ih.n; K, expiration. In the venous pulse the carotid (O and ventricular (V) waves are much the same in inspiration and expiration, but there is a great difference in the length of the second onflow wave (On), which represents the pause. Time marked in seconds. dstill of the heart may be mentioned in connec- tion with vagus arrhythmia as it is brought about by the same mechanism operating more powerfullj'. ! in- patient from whom Fig. 331. was taken was sub- to attacks of syncope which raised the question of heart block. No tracings were obtained during these attacks, but, in view of the evident activity of the vagus inhibitory mechanism in his case, they may have been due to standstill effected through this nerve. Cases have been recorded by Neubiirger id Edinger, Mackenzie, Laslett, and others in which, in a result of some vagus irritation, all the chambers Extra-systoles or premature contractions are beats starting from some cause other than the development of the normal spontaneous contraction. They are produced by the action of mechanical, chemical or nervous stimuli acting on the primitive muscle, and may occur in any part of the heart. They will be more readily understood after a consideration of the terms homogenetic and heterogenetic, which have been recently applied (Lewis) to different types of heart stimuli. Homogenetic stimuli are those which result from the normal development of unstable material in the R.I.J y a see iiiiiiiii mi-iiA jaj^jjijJijLjjajjuuAJLUJUUiJjja^ luum ujjojull Flo. 331. — Right Internal Jugular Vein, above. Right Brachial Artery, below. .4, Auricular wave; C, carotid wave; V, ventricular wave; Os, second onflow wave. Time in 1/5 second. Taken by the writer from a patient of Dr. G. Gordon Campbell. el tjie heart have remained quiescent for two or more ordinary pulse intervals. In some of these cases unconsciousness may supervene. Diagnosis of Sinus Arrhythmia. — The radial pulse will be found irregular in rhythm, but more or less constant in volume. On feeling the pulse and observ- ing the respirations at the same time, a relation may be observed between the phases of respiration and those of the arrhythmia. The heart sounds will be muscle cells with a resulting spontaneous or auto- matic contraction. Under normal conditions they materialize only in the "pace maker" or sinus, but, where there is a defect of conduction so that the con- traction impulse from the sinus cannot spread over the heart, homogenetic stimuli may develop in other parts. Heterogenetic stimuli include all other kinds. We are more or less ignorant of the nature of heterogenetic C19 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES stimuli, but the following varieties may be suggested: irritation from patches of degeneration, high intra- cardiac pressure, distention of the heart by accumu- lated blood, chemical stimuli resulting from faulty metabolism or ingestion of drugs and poisons, and nervous stimuli reaching the heart by the extrinsic nerves. When a heterogenetic stimulus starts a contraction in some part of the heart before the impulse from the sinus has time to reach it the con- traction is called an extra-systole. Such extra- systoles may arise in either auricles or ventricles, or in the junctional tissue between. They are spoken of as auricular, ventricular, and auriculo- ventricular respectively. The contraction wave initiated by an extra-systole may be conducted in any direction like the normal impulse, but more readily downward. Ventricular extra-systoles are usually limited to the ventricle. Auricular extra- systoles are usually conducted down to the ventricle and somewhat less frequently back to the sinus. Auriculoventricular extra-systoles are conducted down to the ventricles and up to the auricles, pro- ducing more or less simultaneous contraction of the two chambers. Vi utricular extra-systoles are produced by some unusual stimulus (heterogenetic) acting on the muscle of the ventricle so as to produce a contraction of that chamber before the impulse descending from the sinus can reach it. In the radial pulse we find the normal rhythm interrupted by a small beat occurring before a regular one is due, and followed by a long pause. The premature beat may be too weak to be felt, in which case the pulse seems to intermit. Tracings from the radial in two cases of ventricular extra-systole are shown in Fig. 332. In both these cases we see the normal rhythm inter- rupted by small premature beats (A'), each of which is followed by a pause longer than the usual pulse interval and called the compensatory pause (4 to 5, -\1 10 10 jV-vJ 7 13 10 10 /\~ B Fig. 332, A and B. — Radial Tracings from Father (A) and Son (/?), Both of Whom have had Ventricular Extra-systoles for Many Years without any Obvious Disease of the Heart. The pulse beats are numbered and the intervals marked in millimeters in B for reference in the text. The extra-systoles are marked by an X. Fig. 332, B). When the intervals immediately before and after the extra-systole are together equal to two normal pulse intervals, we say that the compensatory pause is complete. Such is usually the case in ven- tricular extra-systoles and is so in the two tracings shown in Fig. 332. In B the intervals are marked in millimeters. Hirschfelder uses a different nomenclature to describe the compensatory pause. He calls the interval from the beginning of the last normal beat lo the end of the pause following the extra-systole (3 to 5, Fig. 332, B) a bigeminus; he would say that in this tracing we have a full bigeminus, meaning that the intervals before and after the extra-systole are together equal to two normal pulse intervals. A complete compensatory pause or a full bigeminus is strongly suggestive of ventricular extra-systole, but is not pathognomonic as it may occur with other forms. The pulse beat following the extra-systole (5, Fig. 332, B) is often larger than normal. This is because the long conpensatory pause gives the heart time to fill more completely so that there is a larger amount of blood to be forced out and consequently a greater pulse volume. The fact that the arteries have had more time to empty themselves may also be a factor. Fig. 333. — Ventricular Extra-systole in a Dog from Unknown Cause. RA, Right auricle; RV, right ventricle; X, extra-systole wave in ventricular curve; A, auricular systole; S, ventricular systole; 1% ventricular wave (better first onflow wave); Oi t second onflow wave; S', from fusion of wave due to premature contraction of ventricle with second onflow wave; .4', high wave from contrac- tion of auricle during ventricular systole. Time in 1/5 second. On listening over the heart during a ventricular extra-systole we may hear the normal rhythm in- terrupted by a weak first and second sound occurring before they are due and followed by a long pause. Sometimes the second sound of the extra-systole is not heard, because the ventricular contraction has been too weak to open the aortic valves, "a frustrane contraction" as the Germans call it. In the la case as well as when the pulse is too small to feel, we get A false intermission. Fig. 333 shows an extra-systole which occurred in a dog while tracings W'ere being taken from the right auricle and ventricle with Hiirthle's apparatus. The cause of the extra-systole was unknown. The ventricular contraction marked A* occurred before its time and its effect is seen in the auricular tracing in the wave S' . Shortly afterward the auricle contracted during the ventricular systole producing the wave A'. This wave is high, showing increased auricular pressure on account of the tricuspid valves being closed while the auricle is contracting. A similar high wave is seen in venous tracings in cases of ven- tricular extra-systole and is always very suggestive as it shows that the ventricle is still contracting and keeping the tricuspid valves closed at the time of the auricular systole. In Fig. 333. the compensatory pause is complete as is usually the case with ven- tricular extra-systoles. The intervals 3-4 and 4-6 together occupy the same time as the two preceding normal intervals 1-2 and 2-3. Measurement by the 620 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arrhythmia, Cardiac time tracing below will show that this is the case, and also thai the auricular wave A' occurs at the nor- mal interval after the preceding auricular wave, showing thai the auricular rhythm is unaffected. 334 .1 ami H shows tracings from a case in which every third beat was a ventricular extra- | i,;. 334, A and B. — Tracings from Radial (A) and from Carotid and Jugular (B) in a Case of !'r. Blackader's in "the .Montreal General Hospital. Patient was a middle-aged -woman under meat for indigestion. R. Car., Right carotid; L.T.J., left internal jugular; A", A", extra- iles; A, auricular wave; C, carotid wave; I", ventricular wave; C", carotid wave of extra- le; A\ large auricular wave occurring during ventricular extra-systole. tole. Note the large auricular wave A' during the extra-systole of the ventricle. In this case the .1' waves occur a little prematurely, but as they fol- low the carotid waves at an interval of one-fifth sec- ond or more, it is probable that the extra-systole has started in the ventricle and been conducted backward to the auricle. The reason for the compensatory pause has yet to be explained. It is due to the fact that the systole of the ventricles is still in progress when the auricles contract. During systole the heart is refractory to stimuli, both excitability and conductivity being in abeyance, so that the stimulus from the auricle is unable to descend or else finds the ventricle unable to Apex 1 \ N s 1 '■> sec. X Fig. 335. — Apex Beat Tracing from a Patient of Dr. G. G. Camp- bell showing Interpolated Extra-systole at A\ By measuring between the vertical lines drawn it will be found that thebigeminus including the extra-systole is just equal to the succeeding normal interval respond. The consequence is that the normal beat of the ventricle immediately following the extra- ■ >le is missed, giving rise to the long compensatory pause. In rare cases, where the heart rate is infrequent, the refractory period following an extra-systole has time to pass off before the next regular contraction becomes due. In such a case the extra-systole is wedged in between two normal heart beats and there is no compensatory pause at all. Such an event is known as an interpolated extra-systole and an example i hown in tin. 335, where it is very well -ecu in a i racing from the apex beat. Pulsus Bigeminus. — In some cases every regular heart beat is followed by an extra-systole. This produces a pairing of beats known a- pulsus bigemi- ni] . It is probable that in some way the fir I I .cat of the couple supplie the stim- ulus for the second beat or extra-systole. An example occurring in a dog at the end of a long experiment is shown in I 'ig. 336. Similar cases have been re- ported in man, especially after the prolonged adminis- tration of digitalis. A pulsus bigeminus may also be pro- duced by a true or false in- termission after every two normal beats. These differ- ent forms are very different in their causation. They can- not always be distinguished from one another in the arterial pulse, but from the venous pulse or electrocardia- gram a diagnosis can easily be made. False intermission has already been referred to as due to a weak extra-systole or frustrane contraction; true intermission will be ex- plained later on. Sometimes two or three extra-systoles occur after each normal beat giving rise to pulsus trigeminus and pulsus quadrigeminus respectively. The electrocardiagram in ventricular extra-sys- toles assumes various forms according to the part of the ventricle in which they start. They all agree Fig. 336. — Tracing from the Right Auricle and Right Ventricle of a Dog showing Pulsus, or rather Cor, Bigeminus. This was obtained with Hurthle's apparatus at the end of a long experiment, but the cause of the irregularity was unknown. A, auricular systole; S, ventricular systole; A', extra-systole. however, in differing from the electrocardiagram of the normal contraction which is caused by a stimulus descending from the auricle. Two types produced experimentally are represented in diagrammatic form in Fig. 337. They may be compared with the nor- 621 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES mal shown in Fig. 329. The difference is due to the fact that in an extra-systole the contraction wave and the electric change accompanying it follow a different path over the ventricle to those of a normal beat. Auricular Extra-systoles. — In the arterial pulse the general picture is much the same as in ventricular extra-systoles, but the compensatory pause is usually incomplete. In venous tracings we see the carotid wave preceded by an auricular wave, which may show itself as a separate wave (Fig. 338) or as an augmentation of the preceding ventricular wave (Fig. 339). Although these tracings were taken Fig. 337. — Diagram of the Electrocardiagrams Produced Experi- mentally by Stimulating the Right {A) and Left (B) Ventricles. (Kraus and Nicolai.) from the same patient within a few minutes of one another they present considerable differences suggest- ing that the extra-systoles arose in different parts of the auricle. In Fig. 338 the A wave of the extra-systole is abnormally short showing abbreviated auriculoven- trciular interval and suggesting that the extra-systole originated in the lower part of the auricle or even in the junctional tissues. In Fig. 339 the A wave is fused with the ventricular but evidently makes itself felt before the summit is reached giving us a length- ened auriculoventricular interval and suggesting an extra-systole starting higher up in the auricle. In both cases the compensatory pause is incomplete, sug- R 1 J ~^Y 1 1 sec. X I ^_ Rl 3r 11 16 10 1 18 Fig. 338. — Auricular Extra-systoles. R.I.J., Right jugular vein ; R. Br., right brachial artery; .4, auricular wave; C, carotid wave; V, ventricular wave; Y, X, extra-systoles. Paper travelling 16 mm. per second indicated by horizontal line. Healthy young man patient of Dr. A. H. Gordon. gesting that the impulse traveled up to the sinus causing it to contract prematurely and give the " pace maker " of the heart a new starting-point. In Fie. 339 we have hardly any compensatory pause at all, fifteen and one-half millimeters as compared with i he normal interval of fifteen millimeters, which is also strongly suggestive of an extra-systole arising near the sinus. In Fig. 338 the compensatory pause is longer though incomplete, measuring eighteen milli- meters as compared with the normal interval of six- teen millimeters, which supports the idea that we have to do here with an extra-systole arising farther away from the sinus. 622 In some cases of auricular extra-systole the com- pensatory pause is shortened in accordance with the law of conservation of the normal pulse periods. This means that when an auricular contraction comes be- fore its time the auriculoventricular interval is pro- lunged and when the auricular contraction follows a long pause the auriculoventricular interval is short- ened, both of which facts tend to equalize the ven- tricular intervals. In Fig 340, for instance, the auriculoventricular interval of the extra-systole is longer and that following the compensatory pause is shorter than normal which minimizes the effect on the ventricular rhythm. RIJ 1 sec. RBr 15 Fig. 339. — From Same Patient as Fig.* 338. Showing how auricular wave of extra-systole may be fused with preceding ventricular wave as shown at X in the venous tracing. The effect of the long pause is also well seen in Fig. 341 where the auriculoventricular interval (au- ricular wave) succeeding the pause is much shortened and helps to postpone some of the compensation to the next pulse interval. Similar changes probably occur in the sinoauricular interval in other forms of arrhythmia. In electrocardiagrams from cases of auricular extra- systole the auricular complexes are of variable form according to the part of the auricle in which they originate and are often inverted. The ventricular complexes are usually of normal form as they occur Fig. 340. — Venous Pulse from Case of Auricular Extra-systoles. A, Auricular wave; c, carotid wave; .4', auricular wave of extra- systole superimposed on ventricular wave of preceding cyclo, 1, Normal A— V interval; 2. lengthened A-V interval of extru- sysU>le; 3, shortened A-V interval following compensatory pause. in response to stimuli reaching them by the usual channels from the auricle. Where deviations from the normal occur they may usually be ascribed to some fault in the conducting path (Lewis). A iirirulori utricular extra-systoles are those produced by a stimulus acting on the junctional tissues con- necting the auricles with the ventricles, usually per- haps the auriculoventricular node. They have been produced experimentally and are believed to occur clinically. They form a link between auricular and ventricular extra-systoles and resemble one or other of these according to their exact place of origin. As already stated it is open to question whether REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arrhythmia, Cardiac he extra-systoles shown in Fig. 338 should be re- garded as originating low down in the auricle ir in the junctional tissues. The extra-systole town in Fig. 342 probably originated in the junc- ional tissues, but is of the ventricular type with a ugh combined wave A'. It differs from a ven- ricular extra-systole in that the wave A' comes the auricular contraction is due, which is not ■ til the vertical dot led line is readied, and also in hat the compensatory pause is incomplete. In a ventricular extra-systole the high .1' wave either at the exact time the auricular wave is 1 to. 341. — Tracing Taken From Same < 'ase as Above. Receiver I on neck in such a position as to get auricular wave of r (.1) added to carotid arterial tracing. The auricular belonging to the extra-systole is masked, but the shortened following the long pause is well seen at A". The intervals narked above are in 1/5 second, and show the compensatory >ause to be incomplete. Iue or else sufficiently long after the ventricular beat to allow of conduction backward of the impulse. Moreover the compensatory pause is usually almost lite complete. As to the electrocardiagram of auriculoventricular i systoles, our knowledge is limited to cases in which the auricle contracts a little before the ventricle. In these eases the auricle or P wave is inverted on mt of the stimulus first affecting the lower part of the auricle, the P-R (.4-1') interval is reduced and the ventricular complex is normal. symptoms, while others complain thai their heart gives a great thump or that il seems to flutter or I top. Etiology and Prognosis. — The writer has Been extra-systoles in a great variety of conditions. They are often found in people enjoying excellent health. I ig. 332, .1 and />'. were taken i'l'oiu a father and son aged about liity-iive and thirty, in good health and free from any signs of heart disease. Fig. 340 waa taken from a former laboratory boy who was e - what anemic and had signs of old rickets, but was otherwise well. Figs. 338 and 339 are from a healthy youth of sixteen who had no symptoms and was able to play football and run races up to 220 yards. Fig. 342 was from a man of forty-one with shortness of breath of six: months' duration following physical overwork. At the time the tracing was taken he had a dilated heart and pulmonary edema. 1 have also seen extra-systoles in cases of indigestion, diabetes, and chronic nephritis and in menstruating women. Mackenzie has found them common in old people with infrequent pulse and cardiosclerosis, and in the rheumatic and the neurotic. Extra- systoles may sometimes be attributed to excessive irritability of the heart muscle which may be present either in the healthy or the diseased, sometimes it may indicate the action of a mechanical stimulus like high blood pressure, or a chemical stimulus from some drug or poison like digitalis, or a nervous stim- ulus from some reflex cause. From the variety of causes which may give rise to extra-systoles it can be seen that in any given case their significance is hard to determine. They should suggest a system- atic examination of the patient, including an esti- mation of the field of response. If there are no other symptoms or signs of disease their presence may be disregarded. Treatment of extra-systoles is unnecessary. If there is any concomitant disease, whether circulatory or not, it should be attended to. The writer believes he has seen temporary relief from atropine in doses °f tItt grain three times a day in cases where the thumping or fluttering of the heart has caused annoyance. Fig. 342. — Tracing of Extra-systole at X Believed to be Auricula-ventricular. Large wave A' can only be explained by simulta- neous contraction of auricles and ventricles and it differs from that seen in ventricular extra-systoles in that it occurs before the contraction of the auricle is due. The arterial pulse is poor and docs not show the extra beat, but this is hardly necessary. From a patient of Dr. Ridley .Mackenzie with chronic bronchitis and dilated heart. Sinus extra-systoles are also believed to occur and experimental work has been done on them. We should expect them to resemble auricular extra-systoles but not to show any compensatory pause. Clinically it would be impossible to distinguish them from sinus arrhythmia although their pathology would be different. Sinus extra-systoles would depend on a heterogenetic stimulus acting before the homogenetic had time to develop; sinus arrhythmia in its restricted sense is due to the homogenetic stimuli developing at irregular intervals under chronotropic nerve influence. Symptoms. — Many patients are unconscious of any Auricular fibrillation is the most important of all forms of arrhythmia for two reasons. It is the commonest variety, forming about fifty per cent, of all permanent arrhythmias; and its presence offers clear indications for treatment. Our knowledge of auricular fibrillation has been a gradual growth, and the development of this knowledge is marked by the various terms which have been applied to it at different times. Among these may be mentioned the mitral pulse, the irregular pulse, pulsus irregu- laris perpetuus, the inception of the rhythm of the heart by the ventricle, nodal rhythm, and finally 623 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES auricular fibrillation. We are indebted to James Mackenzie for most of our knowledge of the clinical farts, one of the most important contributions in any field of medicine during recent years. For the com- pletion of our knowledge of the pathology we are under obligation to Cushny and Edmunds and especially to Thomas Lewis. Auricular fibrillation is sometimes spoken of as the absolutely or completely irregular pulse and these terms very well describe the features found on exam- Fig. 343. — Tracing from Case of Auricular Fibrillation. Points marked in venous pulse correspond in time to systolic waves in arterial pulse. Allowing for delay in conduction to the elbow the large waves in the venous pulse are seen to be systolic in time. There are no auricular waves and no negative waves in early systole. These facts mark the venous pulse as of the ventricular form and taken with the irregularity justify a diagnosis of auricular fibrillation. ination of the radials. The radial pulse in an un- treated case is usually frequent, varying in rate from 100 to 200 per minute. In exceptional cases slower rates are found. The pulse beats are felt at irregular intervals and vary greatly in strength. On listening over the heart we often find the heart rate greater than the radial pulse gave us to expect, on account of many beats being too weak to reach the peripheral arteries or even to open the semilunar valves. The sounds heard are irregular in rhythm and vary in 1 see RBr 2 Fig. 344. — Tracing from Case of Auricular Fibrillation under Influence of Digitalis. In the early part of tracing the beats show a characteristic coupling and a frequency averaging 6S per minute. In the latter part of the tracing the coupling has disappeared and the rate has increased to about 106. (Patient referred by Dr. Garrow.) loudness from beat to beat. Many of them are short and sharp like extra-systoles. They may or may not be accompanied by murmurs. Under appropriate treatment the rate of the heart may become less frequent. The ventricular rhythm may ultimately become very slow and fairly regular, resembling that seen in complete heart block, and we may notice the beats occurring in couples. Simultaneous tracings from arteries and veins show a venous pulse of the ventricular form 624 without any auricular wave and without any negative wave X. Fig. 34.3 shows tracings from a man of forty-eight with a dilated heart, but without any murmurs or any history of rheumatism. This tracing was taken before starting treatment. When the patient came into the office his pulse was 132 but when the tracing was taken it had slowed down to 120. Fig. 344 shows tracings from a young man of twenty-two with mitral stenosis and dilated heart, following rheumatic fever. Two months before this Fig. 345. — Tracing from Man of Seventy Recovering from an Attack of Heart Failure with Dyspnea and Edema. At time of tracing edema was gone: dyspnea was noticed only on exertion, heart was moderately dilated, no murmurs, diagnosed as myo- carditis. Pulse is irregular and venous pulse is of ventricular form. Small waves of auricular fibrillation are noticed in some parts of venous pulse (A') . tracing was taken the patient had suffered with severe dyspnea even during rest and was compelled to stay in bed for several weeks. Under rest and digitalis he improved remarkably so that he attended college, was able to take long walks, and even attended one or two dances. A few months later, however, he had another attack of rheumatic fever which failed to respond to salicylates and he died after a month's illness. In some cases of auricular fibrilla- tion the venous pulse may approach the arterial form as seen in Fig. 345, from an old man with myocarditis. R.I.J. c ^J^.PC 9 1 1 X * c JJUJL r 1 l.Br. 1 A^V /> Fig. 346. — Tracing from a Case of Arrhythmia. The arterial pulse is like that seen in auricular fibrillation, but the venous pulse is not of the typical ventricular form. The X negative wave is sometimes well shown and the carotid wave is sometimes preceded by a wave which may be auricular (?). Dunn- the long pause, however, a number of small waves are seen which are probably due to frequent contractions in the auricle, eitbtr fibrillation or flutter. This patient improved remarkably on digitalis and enjoyed life and was able to take walks for somi months. He passed from under observation for a time and discontinued the digitalis. He died about a year later from another attack of heart failure following influenza. Occasionally the venous tracing of auricular fibril- lation shows a succession of small waves during the diastolic pause. These are seen to a slight extent in Fig. 345, but better in Fig. 346. They are usually referred to fibrillary contractions occurring in the REFERENCE HANDBOOK OF Till: MEDICAL S( 1 1 :X< 1 :s Arrhythmia, Cardiac uricle. In Fig. 346 a negative waveXmay be noticed i early systole. This does not necessarily mean !uit the auricles are contracting and relaxing in a ormal manner as the negative wave .V has a double ausation. It is partly due to the drawing in of ilood from the veins by the auricular diastole, and artly to the enlargemenl of the auricle by the f the auricles it disappears when these chambers ass into fibrillation and cease to contract in any ffective manner. We usually' find the presystolic nurmur replaced by a diastolic murmur which is troduced while the blood is being drawn through ■ constricted opening by the diastole of the ven- ricle. Auricular fibrillation is still commoner in niddle and advanced life as a result of degenerative and is often seen without any indication of .alvular disease being present. The postmortem indings in auricular fibrillation have been mostly if the nature of fibrous degeneration of the heart nuscle, especially that of the auricles. In a number < the changes have been well marked at the junction of the superior vena cava and right auricle [S-A node). The symptoms complained of are chiefly various of shortness of breath. Some patients complain of feeling a fluttering or thumping of the heart and can state the day and hour when the irregu- larity suddenly began. /' agnosia. — When the arterial pulse is absolutely irregular in volume and rhythm and the heart Bounds also show great irregularity, auricular fibrillation should be strongly suspected. When at the same time the venous pulse is found to be of the ventric- ular form the diagnosis is almost certain. Whet,; an electrocardiagram can be taken and the /' v.. are found to be replaced by a succession of smaller waves the diagnosis is fully confirmed. Where cardiac compensation is good the veins of the neck may be too empty to give a good venous pulse (racing ami we may have to base our diagnosis on the arterial pulse and heart sounds alone. With a little experi- ence i hese are sufficient for nil practical purposes. Prognosis. — Sometimes this form of irregularity occurs in attacks of shorter or longer duration and there is a return to the normal rhythm. In the majority of cases, however, when once established it is permanent. The prognosis in any given - must be based on the degree of heart failure present. In some cases the fibrillation of the auricles repre- sents one of the last s ;a! j,.^ ; n the downward path of a case of heart failure. In other c:i-r- the patient may live for many years in restricted activity, but comfortable and able to earn a living. Of thirteen unselected cases taken from my notes of the past year or two, six died, two have been lost sight of, and five are still under observation. Of those who died one was under observation two months and died from cardiac failure accompanied by tricuspid regurgitation and signs of venous stasis. One under observation for five months died of chronic nephritis. One under observation for seven months died of rheumatic fever after being temporarily re- stored to activity. One a year after being first seen died from multiple emboli following mitral stenosis. One died a year after my first visit from heart failure accompanying an influenzal pneumonia. One at the end of two years, during which I had several times helped to restore compensation, died under another physician from heart failure which was proved post- mortem to be due to a chronic fibroid myocarditis. Of the five alive two men are earning their living, one old man of seventy-one is enjoying fair health at home, one woman is keeping a boarding house, and one, a married woman, is able to do housework and walk considerable distances at a leisurely pace. One of the men has had the irregularity for twelve years to my knowledge. Treatment. — Auricular fibrillation is the condition in which rest and digitalis give their most brilliant results. If there are no symptoms of heart failure it is necessary only to enjoin caution in the way of physical and mental work, to bring the heart rate down to seventy or less with digitalis and to keep it there. In cases of noticeable heart failure, as shown by shortness of breath on exertion, by marked dila- tation, or venous engorgement, a rest in bed should be insisted on. Three weeks' rest in bed is sufficient for some cases but many need longer than this. During the time the patient is in bed the opportunity should be taken of getting the heart under the in- fluence of digitalis. The form of digitalis is not so important as the selection of the proper case and most cases of auricular fibrillation will be found to be proper cases for it. Mackenzie uses the tincture in closes of twenty minims three times daily until results are obtained. Less than this will often suffice, especially if time is not important. He also uses Nativelle's granules containing one-fourth milligram, three times daily. I have used both these prepara- tions as well as the infusion and several proprietary preparations. In most cases any of them will give results in proper doses. Digitalis should be pushed until the heart is slowed Vol. I.— 40 625 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES down to the point where the patient feels best, which will be found somewhere between forty and seventy per minute. The most desirable rate of heart beat cannot be arbitrarily stated but differs with individual peculiarities. In each case it must be determined by the sensations of the patient and the general experience of the physician. The inexperi- enced physician should be cautious and watchful when the rate gets below seventy. For the full effect of digitalis to be obtained the patient must be under close observation, as otherwise toxic symptoms may develop and the patient may be afraid to persevere with the drug. Among indications for discontinuing digitalis are vomiting, diarrhea, dryness of the mouth, aphasia, drowsiness, and partial heart-block. When all goes well digitalis should be continued until the desired rate of heart beat is attained and then the dose should be reduced to the amount necessary to keep the pulse rate under control. This is usually one-third or one-quarter the daily amount which was necessary to slow it down. Some patients may need one Nativelle's granule daily or twenty minims of the tincture, others only need a granule every two or three days or five or ten minims of the tincture daily. These smaller doses should be continued as long as the patient lives and he should be taught to regulate the dose by his symptoms. The action of digitalis in these cases is believed by Lewis to be that of pro- ducing partial heart-block and protecting the ven- tricles from the multiplicity of stimuli. This allows the ventricles to beat with a more leisurely rhythm which conserves their energy and yet enables them to maintain a better circulation. In cases in which digitalis cannot be taken, which are fortunately rare among those showing auricular fibrillation, the prog- nosis is bad. They must be given a longer rest and have their strength kept up by tonics such as a com- bination of iron, arsenic, and strychnine. In some cases adrenalin seems to be serviceable in doses of twenty to thirty minims of the 1-1,000 solution every two hours by the mouth, or half as much hy- podermicaUy. In cases of very violent heart action with frequent pulse and great distress a hypodermic of morphine gr. J with atropine gr. T lj will often give relief. Auricular Flutter. — Jolly and Ritchie believe that in some cases the auricles may beat regularly and in their entirety but with a frequency of 200 or 300 per minute. To this condition they give the name of auricular flutter. In the cases they report heart block was present but it is conceivable that such a condition might exist without heart block and give a clinical picture scarcely distinguishable from auric- ular fibrillation. It is possible that we have such a condition in Fig. 346, where the small waves f,f,f, due to the auricles are so pronounced a feature. Nodal rhythm was the term used for a year or two by Mackenzie to describe cases of auricular fibril- lation, in the belief that the auricles and ventricles were contracting together under the influence of a stimulus originating in the auriculoventricular node. Since the real nature of these cases has been demonstrated Lewis has come forward with the statement that there are cases corresponding to the condition Mackenzie had in mind when he invented the term and which may properly be called cases of nodal rhythm. Lewis refers to a case of Rihl's and gives one of his own. He also describes an experi- mental example. The main feaures are that auri- cles and ventricles contract more or less together, giving high combined waves in the venous pulse, and the electrocardiagram shows a normal ventricular and an inverted auricular complex with shortened I'-R interval. Tachycardia. — This term has been used by many authors in the sense of frequent heart action under whatever circumstances it may occur. Among the examples which naturally suggest themselves are fever, overexertion, anemia, organic disease of the heart, exophthalmic goiter, and a variety of emo- tional, reflex, and mechanical disturbances which will be discussed in the article on functional dis- orders of the heart. In all these cases the normal origin (homogenetic) and sequence of the heart beat are preserved, but beyond this they have little in common and the advantage of grouping them to- gether under one head is doubtful. Paroxysmal Tachycardia is quite another matter. It occurs in several varieties but they have much in common both clinically and pathologically. It may be spoken of as heterogenic tachycardia because the heart rhythm is due to abnormal stimuli which, so far as yet observed, seem to be of a different nature from the normal stimulus and act upon other parts than the usual "pace maker." Our knowledge of this form of arrhythmia is still limited and the fol- lowing account presents a somewhat dogmatic sum- mary of current opinion, but is in no way to be taken as final. Paroxysmal tachycardia is characterized by sud- den attacks of frequent heart action which last for minutes, hours, or days and then cease almost suddenly as they begin. During the attack the pulse rate is usually very high, reaching 150 or evi D 200 per minute. It is frequently uncountable. ] i some cases the increase of rate represents an exact doubling or tripling of the preexistant rate but the frequency of this occurrence has probably been exaggerated. During the attack the patient may or may not be conscious of fluttering of the hei and sometimes complains of precordial distress or pain. As a rule the sensory symptoms are slight in comparison to the motor disturbance, while in palpitation of the heart the reverse is the case. The breath is short, especially on exertion. The short- ened diastole does not give the heart time to fill - that the circulation suffers. The arteries are com- paratively empty, the face is pale and the vei engorged. In the later stages the liver may be enlarged and there may be edema of the legs and lungs. The heart too may become dilated and signs of tricuspid regurgitation are often found. In attacks of short duration there may not be time for many of these signs and symptoms to develop. The arterial pulse may be regular or irregular. The rate is frequently between 150 and 200 but may vary considerably during an attack. It is wise to confirm the rate by listening over the heart, as some of the pulse waves may not reach the wrist with sufficient force to be palpable. An examination of venous pulse tracings throws considerable light on the nature j of a case but does not always make it perfectly clear. The electrocardiagram is a great help when available. The cases of paroxysmal tachycardia so far re- ported fall under the head of either extra-systoles or auricular fibrillation. Most of them may be classed as due to extra-systoles occurring in a long sei and starting from a single focus in rapid succession. The seat of origin may be in almost any part of the auricles or junctional tissues and more rarely in the ventricles. Some cases on analysis prove 1 1 examples of auricular fibrillation. All the varieties have much in common. All are due to heterogenetic or abnormal stimuli acting upon the heart muscle. The difference between a succession of extra-systi and auricular fibrillation is largely one of degree. In the former the stimuli affect a single focus, in the latter a number of different foci simultaneously. The differentiation of the several varieties is to be made by the examination of venous tracings and electrocardiagram. The general characters ot graphic records are similar to those already descrii for extra-systoles and auricular fibrillation, but tain difficulties arc introduced by the frequent rate. The different waves of the venous pulse are crowded together. The auricular wave may be superimposed 626 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arrhythmia, Cardiac ipon the ventricular wave, or even upon the carotid vave of the preceding cardiac cycle. In the latter ,.,- ii may be hard to determine whether the blend- M c of auricular and carotid waves is to be explained iy the auricular wave falling upon the carotid wave if the preceding cycle on account of the great fre- of the heart rate, or by a simultaneous con- i of the two chambers from a stimulus alfeet- QB the junctional tissues. In cases due to auricular ibrillation the proper auricular waves are ali.-ent and lie venous pulse is of the ventricular form. Before leciding that the auricular waves are absent one ■.elude the possibility of their being present cured by combination with other waves as •xplained above. Light is frequently thrown on a ase by the occurrence of single extra-systoles before ir after an attack. These single extra-systoles often iriginate at the same focus as those of the paro .,1 may help to localize the point from which the utter start. Some cases are complicated by the e of partial heart block. This fact may xplain some instances of exact doubling or trebling >f the rate which has been ascribed to a sudden cturn to normal conductivity. In some cases of achycardia we find an alternating pulse due to a ailure of contractility. The electrocardiagram like the venous pulse is complicated by the fact that the auricular complex lay be combined with some part of the ventricular omplex. Where the paroxysmal beats originate a the auricle the P wave may be seen in its normal nisition but is liable to be combined with the T eave of the preceding cycle. It is often inverted. tYhcre the focus is in the A-Y node the P-R (.1-1) nterval is shortened or absent. In the latter case lie P and fl waves fall together and may- be difficult o analyze. Where the focus is in the ventricle the entricular complex will be found of abnormal form ike those shown in Fig. 338 but, as similar pictures ire occasionally seen where the auricles are the seat if the disturbance, caution must be exercised in (rawing conclusions. For further information about he electrocardiagram in these cases the reader is eferred to "The Mechanism of the Heart Beat" by Lewis, as the subject is too difficult to treat in a short summary like this. In Fig. 348, A and B pulse tracings are shown rom a case of paroxysmal tachycardia during and ifter an attack. The patient, a man of forty-one, same to my office October 24, 1910, complaining of i heavy feeling in the epigastrium, shortness of ireath and inability to lie on his back or left side. Symptoms began suddenly six days before without my known cause. He had had a similar attack four nonths previously lasting two days. The pulse ivas found to be irregular and to vary in rate, being sometimes uncountable. The apex beat was outside he nipple; the heart sounds were embryonic in haracter. A murmur was heard from time to time ivhich was found later to be systolic in time and best Heard at the apex. The tracing shown in Fig. 348, 1. was taken. He was sent home to rest and given incture of strophanthus (strophanthone) in ten- minim doses every three hours. The next day, October 2.5, he reported that he had felt better a few hours after going home and was able to lie on his left side. His pulse was S4 and regular. October 26, pulse 65, regular. Pulse tracings shown in Fig. 34S, B, taken. October 29, pulse 70. Apex beat in nipple line, c murmur still heard at apex. Felt all right. Passed from observation. Comparing the tracings taken during and after the attack. Fig. 348, A and B, we seem justified in marking as partly auricular the pointed waves A' seen in .4. These occur, however, at the time of the ventricular systole and are superimposed upon the carotid waves. As they preserve this relative position with varying lengths of pulse intervals, they must belong to tin- same cardiac cycle as the carotid es on which they fall. These facts justify us I think in classing this case as due to extra-systoles originating in the junctional tissues in or near the .1-1 node. (in account of 1 he difficulty of getting good tracings of the -mull frequent waves in I cases there ts often room for difference of opinion as to the interpretation of the tr;n-itiL.'s. in th of facilities for taking an electrocardiagram we have often to depend a good deal on circumstantial evidence. Fig. 34S, A and B. — Tracings from a Case of Paroxysmal Tachycardia During and After an Attack. R I J, Right internal jugular; R. Br, right brachial artery. The upper figure is marked with vertical lines marking what are believed to be the beginnings of the brachial pulse beats and the points in the venous pulse corresponding to these in time. Allowing for delay in trans- mission the A' waves are seen to be systolic in time and by com- parison with the tracing below seem to be partly auricular in origin. The pulse rate in Fig. A is about 190 to 200 per minute. Patient of Dr. Herbert Tatley. Pathology. — A disordered action of the heart resembling paroxysmal tachycardia may be induced in animals by tying branches of the coronary arteries or by applying the strong faradic current to the auricles. It does not seem possible to produce the same result by any procedure directed to the nerves when the heart is in a normal condition. There is some evidence however that an attack may be pre- cipitated by- stimulation of the cardiac nerves when the heart is already in an abnormal condition. The postmortem changes are not constant. In different cases valvular disease, coronary sclerosis, degenera- tion of the heart muscle, and various nerve lesions have been found and in still other cases the findings have been negative. We have to admit that we are ignorant of any constant underlying cause. The principal seat of the disease is probably in the heart 627 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES muscle, but emotional and reflex causes have an undoubted influence in precipitating attacks. Diagnosis. — Paroxysmal tachycardia has to be distinguished from simple acceleration of the heart due to anemia, fever, exophthalmic goiter, etc., from persistent frequency of the heart rate and from palpitation. The diagnosis rests on the occurrence of the attacks in recurring paroxysms, the high rate suddenly attained, the comparative absence of sensory phe- nomena such as are common in palpitation, and the evidence in the venous pulse and the cardiogram that the pace maker of the heart has been changed. Prognosis. — The prognosis depends to a great extent on the duration, severity and frequency of the attacks in individual cases. A number of cases have been reported in which recovery occurred, others have had repeated attacks for years without life being endangered, and in others the attacks have exhausted the heart and led after one or more seizures to a fatal termination. Sometimes the tachycardia becomes permanent for a while before death occurs. The best guide to prognosis is the extent to which indications of heart failure appear. Of these the most important are dilatation of the heart, shortness of breath, enlargement of the liver, and dropsy. Treatment. — Many methods have seemed to succeed in individual cases and none is of universal applica- bility. Absolute rest seems indicated and is usually to be recommended although Fairbrother found in his own case that violent exercise cut short the attacks better than anything else. The most ap- proved measures have as their primary object the stimulation of the vagus. This may often be accom- plished by mechanical means. Success in varying de- grees has been reported from swallowing movements, from Valsalva's experiments of taking a deep breath and exerting strong expiratory pressure against a closed glottis, and from pressure against the verte- bral column of one or other vagus nerve where it lies beside the carotid artery outside the thyroid cartilage. These mechanical methods succeed best at the begin- ning of an attack. Where they fail strophanthus may be tried either intravenously or by the mouth. Digitalis acts well in some cases and is probably safer than strophanthus, albeit a little slower. 'Where all these measures fail a trial may be made of nerve sedatives like morphine, bromides, or valerian. An ice-bag applied to the precordium has been recom- mended. Between the attacks any derangement of the nervous, digestive, or sexual systems should' be appropriately treated and the general health should be looked after. Excesses in food and beverages should be warned against and overstrain of all kinds forbidden. The possibility of emotional and mental strain should be considered. If any organic disease of the heart is present it may require attention. Heart failure may be combated by rest and digitalis. The results of treatment should be published as more light is needed. Heart-block is a form of arrhythmia which looms up too large in the perspective of most physi- cians. It may be that the term is catchy and easily understood, or it may be that it has borrowed im- portance from the great names of the past which have been associated with it. To many it is one of the first things thought of when an irregular pulse is encountered and yet it is comparatively rare. In any large general practice sinus arrhythmia, extra- systoles, and auricular fibrillation must be of al- most daily occurrence but months and even years may pass before a single case of heart-block is seen. Definition ami Subdivisions. — Heart-block may be defined as a solution of physiological continuity be- tween different parts of the heart. Under heart- block, however, it is convenient to consider all con- ditions attended bv a depression of conductivity. 628 The following subdivisions may be made: According to location. 1. Sinoauricular heart-block. 2. Auriculoventricular heart-block. 3. Intraventricular heart-block. According to degree. 1. Lengthened conduction time. 2. Partial heart-block. 3. Complete heart-block. Auriculoventricular heart block which is the com- monest and most important form will be considered first in the three degrees in which it occurs. Lengthened A-Y Interval. — The A-V interval may be measured by calculating the time from the begin- ning of the A wave (auricular systole) to the beginning of the C wave (ventricular systole) in the venous pulse, see Figs. 327, 331, 340. It may also be estimated by calculating the time from the beginning of the P wave to the beginning of the R wave in the electro- cardiagram {P-R interval). This is rendered pos- sible by the fact that a time marking in one-fifth second can be photographed on the same plate with an electrocardiagram. The A-V conduction time as estimated by either of these methods is found to l)e from .1 to .2 second normally. It is claimed by Lewis that it is commonly a little shorter when e mated from the electrocardiagram than when the venous pulse is used, but the difference is slight. During the refractory period conductivity like other properties of the heart is temporarily in abeyance and recovers gradually. After a short pause the con- duction time is long and after a long pause the con- ductivity is at its best as has been pointed out in writing about auricular extra-systoles. In view of the above it seems like a paradox that we usually find a shortened A-V interval with frequent heart rate and a lengthened interval with an infrequent rate. This is to be explained by the fact that con- ductivity and rhythmicity are both under nerve control and are usually influenced in the same direction. Where the A-V interval is more than 0.2 second it is considered abnormal and it may be lengthened to 0.3 or 0.4 second or even to 0.S second. Where lengthening of the A-V interval is found we may suspect some degeneration of or interference with the junctional tissues between auricle and ventricle. The part affected may be either the A-V node or the bundle of His. Mackenzie has seen a case shofl lengthened A-V interval for years without develop- ing any arrhythmia, but these cases should be watched for early signs of partial or complete heart- block. It may also be said that lengthening of the A-V interval is suggestive of widespread degeneration of the heart muscle, such as is seen in many old people with arteriosclerosis. The most important practical point in connection with lengthened A-V interval is the bearing of this defect upon treatment. Digitalis has been shown by Mackenzie to have a tendency to produce heart- block in patients where the conductivity is already depressed and in such cases it should be given with discretion and its effects watched. It is going too far to say that digitalis should not be given at all in these cases as it is often useful in restoring i to the heart, but it should be discontinued as soon as any tendency is shown for the ventricle to drop beats. The following case will serve as an illustration of lengthened A-V interval. An old lady of eighty with a past history of rheumatism came under my care with symptoms of heart failure following over- exertion. There were signs of considerable dilata- tion and a mitral systolic murmur. She was ordered to bed and given tincture of digitalis in doses of thirty minims per day for several weeks. During this time her heart became smaller in size and the REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ i I li\ lliini ... < ardlac murmur disappeared, bul she began to suffer from dry mouth and somnolence. On listening over the heart one day 1 heard it drop alternate heals three limes ill succession anil then resume ils regular rhythm. 1 suspected partial heart-block and discontinued the digitalis. The next day the tracing shown in Fig. 349 was taken in which it can l>e seen that the .1-1' interval is ahout one-third second or considerably longer than normal. She was given a rest from digitalis and no more dropped beats were observed. Fie.. 349.- Lengthened .1-1' Conduction Time. Jugular vein Brachial artery below, .4, Auricular wave; C, carotid I , ventricular wave. Horizontal line shows distance [led by kymograph in one second when well started. A-V interval about 1/3 secoud. Partial Am irulan utricular Heart-block. — In cases where the conductivity is greatly depressed but not entirely lost the junctional tissues may from time to time fail to conduct the impulse from auricle to ventricle so that the latter is not stimulated and drops a beat. In Fig. 350 a tracing is shown from :in old man of eighty-four by whom several different kinds of irregularity were exhibited. To the right of the tracing it may be seen that the ventricle responds only to every second beat of the auricle. It is somewhat surprising to find that when the ven- tricle does respond the A-V interval is normal, one- venous tracing fii i a normal A-V interval and then a gradual lengthening of conduction time which becomes longer with each cardiac cycle until ai la I a ventricular heal is dropped anil then ue start all over again. Partial heart-block may occur in many different degrees such as one ventricular beat dropped out mi rare intervals or after every third or every second auricular heat. In some eases there may be three or four or more auricular beal to one ventricular. lino can find described in the literature every deg from Lengthened A-V interval through varying degrees of partial heart-block up to complete heart- block. Complete Auriculoventricular HeartMoch. — In this condition no relation whatever can be established between the contraction of auricles and ventricle . The auricles will be found heating from sixty to a hundred or more times a minute, whili the ventricular rule may he twenty or thirty or forty. Where an occasional ventricular heat, seems to follow a heat of the auricles it can lie seen to lie only a coincidence. Attention is usuallyfirst attracted by the infrequent pulse, but the real nature of the case is de QStrated only by an examination of a venous pulse tracing. In Fig. 35] a tracing is shown from a patient of Dr. A. II. Gordon in the Montreal General Hospital. The patient was a, man of thirty-six with a dilated heart and an almost continuous murmur heard over a large part of the precordium. He showed pronounced arteriosclerosis, but there was no history of syphilis. He was said by his friends to be subject to frequent attacks of mental excitement, but did not have any of these while under observation. Some time after leaving hospital he became so maniacal in one of his attacks that he was taken off to the police station, where he died. During his stay in hospital his pulse kept about thirty per minute and was not affected by full doses of atropine. On exertion he readily became dyspneic, but there was little or no change in his pulse rate. RBr IU-11 II I I II LLL I I I I I I I I I I I I I ' I I I II I I ' I I I I I I I I I I I I I I Fig. 350. — Tracing from a Man Eighty-four Years Old, patient of Dr. A. D. Blackader in the Montreal General Hospital. Admitted with complaints of weakness and shortness of breath. Heart dilated, systolic and diastolic murmurs present at first, but later disappeared. Clinical diagnosis of myocarditis. Patient was in hospital for six weeks ami was discharged improved and able to walk .ibout. R I J, Internal jugular vein; R Br, brachial artery; A, auricular wave; C, carotid wave; A\ premature auricular wave; S, wave ascribed to systole of right ventricle. This tracing is believed to illustrate three different kinds of arrhythmia. 1. Hemisystole (1). 2. Ventricular extra-systole (2). 3. Partial heart-block (3, 4, 5). Over the figure 1 in the tracing are seen two waves A' and S, which occur before the carotid wave and therefore before the systole of the left ventricle. These waves resemble the A and C waves of ither cardiac cycles and are believed to represent the contraction of the right auricle and right ventricle, constituting a hemisystole. They are followed by an ordinary C wave due to the contraction of the left ventricle. In the absence of an esophageal tracing there is no way of telling when the left auricle contracts. Note that the A' wave is premature, which may help to explain the imperfect conduction. At 2 is seen a ventricular extra-systole with a high combined A and C wave. 3, 4 and 5 show auricular waves which are not followed by any contraction of the ventricles constituting partial heart-block. It is noteworthy that where the ventricle follows the auricle the A-V interval is less than 1/5 second and therefore normal. fifth second. Other observers have also reported normal conduction time alternating with partial or complete heart-block. Some have assumed that in these cases it is the excitability of the ventricle that is depressed. Such an explanation will not serve in this case, as a second or two before the ven- tricle begins to drop beats in Fig. 3.50 we see a ventricular extra-systole which is scarcely compatible with loss of excitability, but rather the reverse. In some cases of partial heart-block we see in the In complete heart-block the contraction wave is unable to descend to the ventricle so that the latter either stops altogether or beats in response to its own homogenetic stimulus {idioventricular rhythm). Experiment seems to indicate that the more suddenly the heart-block becomes established the more liable the ventricle is to stop permanently. The most dangerous time in a case of heart-block is at the moment when a partial heart-block is changing to the complete form and some unexplained cases of 629 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES sudden death are probably of this nature. When the idioventricular rhythm is once well established it may go on for months or years with little change. The rate of the ventricles is usually about thirty, but may for a time be as slow as eight or less, and it has been observed as frequent as sixty per minute. Pathology. — Heart-block may be induced in animals in all its degrees by compression or severance of the bundle of His. Similar effects have been seen to follow the intravenous injection of poisonous doses of digitalis. Temporary heart-block has been pro- duced by stimulation of the vagus and by asphyxia. In man nearly all cases so far observed have been Stokes-Adams Disease or Syndrome. — Definition: •' A condition of slow pulse with syncopal, apo- plectiform or epileptiform attacks associated either with (a) derangement of the junctional system of the heart or (b) disease of the nerve centers of the vagi or of the nerves themselves" (Osier). "The cerebral symptoms are a direct result of a circulatory disturbance following a momentary fail- ure of the left ventricle. They vary in ditT. cases. Attacks resembling petit mal are perhaps the most common with twitching of the limbs and face. The epileptic fit with its orderly sequence of events is rare. A slight aura may precede an attack Fig. ool. — Tracing from a Case of Complete Heart-block. Patient of Dr. A. H. Gordon in the Montreal General Hospital. Internal jugular vein above. Apex beat below. The ventricular rate was very constant at 30 per minute so that each apex beat interval corresponds to 2 seconds. .4, Auricular wave. Vertical lines show points of time in venous pulse corresponding to the beginning of ventricular systole as shown in apex beat. Note the total absence of any constant time relation between the auricular waves and the ventricular systole. The auricles contract nine times while the ventricles contract four times. associated with some disease or anomaly of the A— V bundle. The causes are various and include syphilitic gummata and other tumors; fibrous, calcareous, and atheromatous degeneration; infarction, necrosis, and ulceration; atrophy from pressure or stretching or from sclerosis of the coronary arteries; lymphocytic and fatty deposits; rheumatic and diphtheritic infection. Vagus stimulation from swallowing, pressure, or the administration of digitalis may cause temporary increase in a preexistent block. Fulton and Judson have reported an instance of heart-block occurring in a father and two children which they ascribe to con- genital defect. Cases of partial or complete heart- block alternating with periods of normal conduction time and those rare cases in which no disease of the A-V bundle has been found at autopsy cannot at present be explained. S imptoms. — The symptoms vary according to the degree of cardiac failure present. The complaint to be expected is above all shortness of breath on exertion. To this may be added various degrees of cardiac palpitation, oppression, and pain. In some cases attacks of angina have been seen. Cya- nosis, dropsy, and other signs of heart failure may be present. The cerebral symptoms are interesting and important. In some cases symptoms of neuras- thenia may be present and the patient may be nervous and apprehensive. In other cases transient vertigo or fainting attacks may cause alarm. In still other cases attacks occur in which cerebral symptoms are still more prominent and which are known as the Stokes-Adams disease or syndrome. The Stokes-Adams syndrome and heart-block are by no means synonymous and each may occur without the other. All grades of heart-block may occur without definite cerebral symptoms and attacks which fully meet the definition of Stokes-Adams di ea e are frequently seen from other causes than heart-block. The two conditions are so frequently I. however, that this seems the most con- venient place to describe the Stokes-Adams disease. and the patient may be able to ward it off. After recurring for a year or more the attacks may cease; in other cases they become extraordinarily frequent, thirty, fifty, or even one hundred and fifty in a day. and consist of brief periods of loss of consciou- with twitchings of the muscles. During these paroxysms the pulse rate may fall to six or eight and there may be prolonged intervals between the ven- tricular beats" (Osier). The Stokes-Adams syndrome is most frequently seen in association with heart-block (eardim- gro under two conditions; first, when a partial heart- block suddenly becomes complete, and second, when in a complete heart-block the ventricular rate ■ denly becomes less frequent. When a patient is the subject of partial heart-block some slight cause may suffice to render the block complete and the ventricle may be tardy in assuming its independent rhythm. It may remain perfectly inactive for many seconds (more than two minutes — Stengel), or it may I u it li an extremely slow rhythm for a time. In either case the cerebral circulation suffers and some form of "attack" occurs. The causes which render the block complete may be various such as over-exertion, nerve influence, or drug action and in some cases they escape detection. In complete heart-block the ventricular rate may suddenl}" drop from thirty or forty a minute to eight or ten, or the ventricles may stop entirety for a time with a similar disturbance of the cerebral circulation. The other or neurogenous group of cases, not due to heart-block, are caused by lesions of the medulla or vagi and present similar symptoms of slow pulse and cerebral disturbance. Among the principal causes are the following: 1. Fracture or dislocation of the cervical spine. 2. Narrowing of the vertebral canal or occipital foramen. 3. Tumors of the medulla or its neighborhood (cerebellum). 630 REFERENCE HANDBOOK OK THE MEDICAL SCIENCES Arrhythmia, Cardiac I. Sclerosis of t ho medulla due to disease of the , tebral and basilar arteries. ,. Vagal neuritis. i. Pressure on the vagi in the neck. '. Functional affections of the vagus as a cause of i irt-block are regarded by Osier as of doubtful , urrence. \ case has been reported by James in which syn- I ial attacks resembling those of Stokes- A. lam ■ase were caused by recurrent groups of ineffect ual ra-systoles (frustrane contractions). Tt, may be cd here that in some cases of complete heart -hi nek radial pulse shows numerous tiny elevations i ing the ions pause. These are believed to be the beating of the auricle against the aorta I I must be carefully differentiated from extra- 1 1 iles such as those described by James. oris. — There is usually nothing; character- i c about the symptoms of the slighter forms of k. Lengthening of the A-V interval is covered only when a venous pulse tracing or an i 'trocardiagram is taken. In some cases of length- i d conduction time a gallop rhythm is heard over heart. This is due to the fact that the slight ml produced by the auricular systole is heard I arately from the first sound when the A-V interval i I'tigthened, but is fused with it when the conduction c is normal. Partial heart-block gives rise to an gularity of the pulse which may be noticed in the t lial, but it usually requires a venous tracing for | differentiation from other forms of arrhythmia. complete heart-block attention is arrested by the i rcquency of the pulse or by the cerebral symptoms. ] the case of the latter, senile bradycardia accom- lied by vertigo and true epilepsy must be excluded. ■ sounds heard over the heart in complete heart- I ek vary according to the condition of the heart i -cle and valves. In many cases weak sounds due t the auricular systole are heard in the intervals I ween the ventricular beats. Griffith has recently Biwn attention to a striking alteration in the first id which is sometimes heard in complete heart- lick. It consists of a "singularly thumping and : phatic sound" which is heard every few beats and i iscribed by Griffith to a simultaneous contraction i auricle and ventricle. In complete heart-block, i in other forms, venous tracings and the electro- i diagram are of great help in making the diagnosis i tain. The electrocardiagram shows complete i sociation in the time relations of the P wave and I ! ventricular complex. The ventricular complex i usually of normal form indicating that the idio- ■ itrieufar impulse originates above, presumably i the main trunk of the bundle of His below the seat disease. Atropine is often administered in full to determine how much of the block can be i noved by paralyzing the vagus endings. Any lick removed by atropine may be considered of i irogenic origin. The block that persists in spite ; atropine may be ascribed to local disease in the I adle of His. It is important to determine the iture of the disease present and especially its ise. Slighter forms are more often due to rheu- i it ism, the more severe forms to syphilis. Where the ••stion of syphilis is in doubt one should apply ■ therapeutic test of a thorough course of iodide. Prognosis. — The prognosis depends largely on the use. In eases associated with infectious fevers presence of heart-block adds to the gravity of the '■, bul where recovery from the fever takes place c heart-block is likely to disappear in a short time. philitic cases are the most favorable. Most eases complete heart-block which have recovered have '■n of syphilitic origin. In the senile and degenera- c oases the course is often very chronic. The nkes- Adams attacks often cease, however, when the event ricular rhythm is fully established. Some of thee patient-; Buffer with marked heart failure, but other- are able to get about and even to earn a living. Osier gives five to six years as the average duration of life, but some have lived for t weilty J eai or more. As in other myocardial affections sudden death is apt to occur while the patient is up and about. This happened in ten of Osier's cases out of a total of twenty. Treatment. — There is no specific treatment except for the syphilitic cases in which iodide ef potassium in full doses should be given and mercury or salvar- an if necessary. There is s difference of opinion as to whether iodide is likely to do good in the arteriosclerotic cases. Strychnine is another drug in which some have confidence. Heart failure is to be met chiefly by rest and regulation of the diet and mode of fife. Digitalis is regarded as contraindi- ca,ted in partial block, but in complete heart-block with indications of cardiac failure it should certainly be tried and will sometimes do good. Intraventricular heart-block occurs in two forms, hemisystole and ataxia of the heart muscle. Hemisystole. — In the dying hearts of animals one Ventricle often stops while the other goes on beating. The possibility of one sided ventricular contractions in man has been disputed, but the evidence that it sometimes occurs is now considerable. Von Leyden, beginning in 1S68, reported a number of cases, but his work has not been universally accepted. Riegel, for instance, explained the cases as frustrane contrac- tions (weak extra-systoles). Mackenzie in his book, "The Study of the Pulse," presents one very convincing case (page 294) of independent contraction of the right ventricle in a boy dying of dilatation of the heart from mitral stenosis. He gives another case almost as convincing in which the right ventricle seemed to contract more often than the left. Hewlett reports a case following the administration of stro- phanthin, in which the ventricular contractions some- times caused waves in the venous pulse with little or no effect on the apex beat. The presumption was that the right ventricle was contracting alone. In the same case it was shown that the right ventricle sometimes began its contraction distinctly later than the left as though the contraction impulse to the right ventricle had been retarded. The parallelism to lengthened A-V interval is obvious. Stengel and Pepper report a case showing various forms of heart- block in which the auricular wave was followed by a beat in the radial pulse, but not by any C wave in the venous pulse. They interpret this to mean that the left ventricle had contracted without the right. They agree with the writer that the C wave in the venous pulse has little or nothing to do with the caro- tid, but is a wave sent back through the tricuspid valves by the contraction of the right ventricle. The tracing shown in Fig. 350 shows what is believed to be a hemisystole at the point marked with the figure 1. There are indications here that the right auricle and ventricle contract in proper sequence and the left ventricle follows later. Ataxia of the Heart Muscle. — Schmoll has reported a case in which the right ventricle and perhaps part of the left contracted independently of the principal mass of the left ventricle. He compares such cases to the incoordination seen in the body in such diseases as locomotor ataxia and for partial contractions of the heart he suggests the term ''ataxia of the heart muscle." Evidence of partial contractions of the heart muscle is sometimes afforded by the occurrence of weak ventricular contractions interrupted by stronger ones without any pause between the two. It is probable that some cases of pulsus bigeminus such as that shown in Fig. 336 are of this nature. The most extreme degree of ataxia of the heart is fibrillation. This is common in the auricles, but fibrillation of the ventricles is probably incompatible with life so 631 Arrhythmia, Cardiac REFERENCE HANDBOOK OF THE MEDICAL SCIENCES that our knowledge of it is limited to the hearts of dying animals. Diagnosis. — The recognition of intraventricular heart-block is to be effected by the use of all the methods at one's command. Besides tracings of the arterial and venous pulse and apex beat, esopha- geal tracings may be helpful, as in the case reported by Schmoll. It is onty through the esophagus that we can get a tracing from the left auricle. Kraus and Nicolai claimed at one time that separate con- tractions of the right or left ventricle gave charac- teristic clectrocardiagrams by which they could be recognized, but this is called in question by Lewis who makes the statement that the authors have themselves receded from this position. Prognosis. — The presence of hemisystoles or ataxia of the heart muscle must always indicate serious changes in the heart and it seems only a step from these conditions to fibrillation of the ventricles and death. From the fact, however, that the case figured in Fig. 350 and also those reported by Hewlett and by Schmoll, left hospital improved, the condition cannot be regarded as necessarily pre- saging speedy dissolution. Treatment. — This must be carried out on general principles. Schmoll's patient was given digitalis for his general heart failure with benefit. Stengel and Pepper's patient improved under atropine and the block disappeared. Dr. Blackader's patient, Fig. (3.50), improved during his stay in hospital where the principal drugs given him were strychnine and digitalis. In Hewlett's case the block seemed to be caused by the administration of strophanthin and passed off when the drug was discontinued. Sinoauricular block may be produced in animals by ligating, crushing, or cooling the sinoauricular border. Under these circumstances the sinus con- tinues to beat as before and the auricles after a period of standstill begin to beat with a slower rhythm of their own. Lesser degrees of injury may produce a partial sinoauricular block with one beat of the auricle to two of the sinus. A parallel condition in man would be a block between the sinoauricular node and the auricles. In the absence of any cri- terion of sinus activity it is difficult to demonstrate it clinically, but its presence has been inferred on circumstantial evidence by Hoffman, Hewlett, and Gibson. To it have been ascribed sudden changes in the rate in paroxysmal tachycardia, and also certain cases where both auricles and ventricles have dropped a beat without permanent dislocation of the cardiac rhythm. Bradycardia is the opposite of tachycardia and means slow or, better, infrequent pulse. The con- ditions embraced under this term do not form a clinical entity, but the term is a convenient one to use in any given case until we are able by careful analysis to allot it to its proper class. We may classify temporarily as bradycardia any pulse below fifty per minute. On further study these cases may turn out to be: 1. Complete heart-block. 2. Combinations of auricular fibrillation with heart-block. 3. Extra-systoles replacing every second beat and too weak to be felt at the wrist. 4. Pulsus alternans in which the weak beat is not felt. 5. True bradycardia in which the whole heart beats at a slow rate, but in normal sequence. True bradycardia may result from any of the fol- lowing causes: 1. Personal or family idiosyncrasy. These cases are not usually pronounced in degree and may be seen in individuals otherwise in perfect health. 2. Neurogenic, from lesions of the medulla, upper spinal cord, or vagi nerves, from functional disorders 632 of the nervous system such as melancholia, hysteria and neurasthenia, and from efforts of the will as has been reported in oriental fanatics. 3. Reflex, from painful and other affections of the thoracic, abdominal, and pelvic viscera. Notable examples are hepatic and renal calculi. 4. Infective, as influenza, diphtheria, and typhoid. 5. Toxic, as seen in poisoning with lead or digitalis and in autointoxication from constipation, jaundice or nephritis. 6. Cardiac, as seen in the bradycardia of senile degeneration of the heart. These cases must be analyzed in accordance with the principles already laid down and treated accord- ing to the causes which seem to be at work. Pulsus alternans is the name given to regular alternation of strong and weak pulse beats at ap- proximately equal intervals. An example borrowed from Mackenzie is shown in Fig. 352. Where there is any irregularity in the pulse intervals in pulsus alternans it is usually the weak beat that is delayed. This has been explained by a depression of A-V conduction at the time of the weak beat (Wenckebach). It has also been ascribed to a longer presphygmic interval due to the weak beat taking longer "to open the semilunar valves (Hering). Fig. 352. — Pulsus Alternans. The numbers show a slight pro- longation of the pause before the smaller beat, in contrast to what occurs in pulsus bigeminus. (Mackenzie.) In an individual case the venous pulse should show which is the proper explanation. The venous pulse is usually normal in form. Pulsus alternans must be differentiated from pulsus bigeminus due to extra-systoles. This may be done by noting the length of the pulse intervals, and by examining the venous pulse for signs of extra-systoles. In pulsus bigeminus a longer interval precedes the large beat. In pulsus alternans the intervals are equal, or if there is a slight difference the longer interval precedes the small beat as already explained. Pulsus alternans is regarded by Wenckebach, Mackenzie, and others as due to a depression of con- tractility. It is seen in senile hearts where there is considerable fibroid degeneration, and after exhaust- . ing strain, such as after an attack of paroxysmal tachycardia. It is frequently associated with at- tacks of angina pectoris. Where predisposition exists the onset of pulsus alternans is often deter- mined by exertion or excitement. Sometimes it <•■ ushered in by an extra-systole. Where contractility is impaired the large beat following an extra-systole exhausts the heart muscle so that it has not time to recover completely before the next impulse descends and it responds with a weak beat. The weak beat being small and of short duration, the heart has a longer rest before the descent of the next impulse and responds with a stronger beat and so the alterna- tion goes on. The diagnosis of pulsus alternans can be made provisionally by feeling the radial pulse. The alter- nating force combined with the regular rhythm of the beats is often recognizable. Some have noticed variations in the strength of the heart sounds esp< - cially in cases where systolic murmurs are present. The diagnosis is confirmed by taking tracings of the arterial and venous pulse by which extra-systoles may be excluded. The diagnosis is sometimes rendered difficult by the fact that extra-systoles and pulsus alternans may be present in the same tracing. REFERENCE HANDBOOK OF THE MEDICAL SCIEXCES Ari'h> thini;u Cardiac In some of these cases the irregularity in rhythm and volume is so great that the question of auricular fibrillation may lie raised (W'imlle), but the latter ma y be excluded if the venous pulse is found to be oi the auricular form. Pulsus alternans may also be plicated by the presence of intraventricular heart- block. In apex beat tracings the alternation may or may not show. Where the ventricular beats seem to he iif equal force the alternation in the arterial pulse be explained by variation in the tilling of the ricles due to unequal activity of the auricles. electrocardiagram does not give constant results. the complexes are of normal form. There may be -nation in the height of the waves, but there is onstant relation between them and the size of the arterial pulse. The prognosis is, generally speaking, unfavorable. As this form of irregularity indicates exhaustion of heart muscle, the degree of recovery that may be cted must depend to some extent on the causes produced it. The prognosis is naturally better in coming on after severe strain than in those due to degeneration of the heart muscle in the absence of al stress of work. According to Mackenzie the ecta of this form of irregularity usually succumb within a few years. Treatment. — This form of arrhythmia more than any other calls for absolute rest. Digitalis is con- traindicated as drugs of this class have been seen to ease the defect. Chloral may do good by pro- ting sleep and lowering blood pressure. Sugar in large quantities as a heart food, and tonics like iron arsenic should be of benefit. A patient lately under my care did not improve much after several weeks in bed with treatment along the above men- tioned lines, but began to improve as soon as he was given adrenalin. This was first given hypodermic- ally in doses of ten to fifteen minims every two hours, and later by the mouth, six to eight suprarenal tablets daily. The result was that attacks of pre- cordial pain with pulsus alternans ceased and his ability to stand moderate exertion returned. Pulsus intermittens and Pulsus deficiens are names without exact pathological significance. Pulsus intermittens is used for dropping of beats in the radial pulse. Pulsus deficiens is reserved for cases where the ventricle itself drops a beat. A beat may be dropped by the ventricle as a result of partial or complete heart-block. A beat may be missed from the arterial pulse as a result of heart-block, and also from a beat of the ventricle being too weak to open the semilunar valves or to reach the peripheral arteries, as in early extra-systoles or in extreme degrees of pulsus alternans. Flo. 353. — Pulsus Paradoxus (Schrotter). Showing how the puke volume approaches the vanishing point at the end of each inspiration. Pulsus paradoxus is the name given by Kussmaul to a diminution in size or absence of the pulse during inspiration. It is often spoken of as pathognomonic of adherent pericardium, but this is not the case as it is seen in cases of pericarditis with effusion (Roberts) , splanchnoptosis (Hirschfelder), and to a moderate degree, it is said, in some normal individuals. A converse condition known as Riegel's pulse is the diminution in the size of the pulse during expiration which is seen in some cases of adhesion between the heart and the anterior wall of the chest. These forms of arrhythmia can usually be recognized by palpation of the pulse while listening to the heart sounds and watching the re piration. Their diagno tic significance is probably not very great, 'they usually indicate some pulling upon the meal vessels which narrows their lumen at certain stages of respiration. The active agent is often a fibrous band resulting from luediasl init is which compresses the aorta when drawn down by the diaphragm in inspiration or by the descent of the ribs in expiration. Sometimes the great veins are also compressed, producing ta i and -welling in the veins of the neck. Very few tracings have been published. That shown in 1 i^r. 353 is borrowed from ScbrStter's article in Nothnagel's Encyclopedia. The treatment is that of the underlying condition. Some eases of adherent pericardium have been bem - Sted by resecting parts of the third, fourth, and fifth ribs over the heart (cardiolysit I. William S. Morrow. Bibliography. I desire to express my indebtedness to the following Looks, which have; been freely consulted: Allbutt and Rolleston's System of Medicine. Articles by Arthur Keith, Sir William Osier, and F. T. Roberts. Hill's Further Advances in Physiology, The Heart, by Martin Flack, and Pulse Records, by Thomas Lewis. Diseases of the Heart and Aorta, by A. 3). Hirschfelder. Functionelle Diagnostic und Therapie, by Aug. Hoffmann. Text-book of Physiology, by W. H. Howell. Mechanism of the Heart Beat, by Thomas Lewis. The Study of the Pulse and Diseases of the Heart, by James Mackenzie. Nothnagel's Encyclopedia of Practical Medicine, article by L. V. Schrotter. Arrhythmia of the Heart, by K. F. Wenckebach. The following have also been referred to in the text or laid under contribution; Barker, L. F. Electrocardiography and Phonocardiography. The Johns Hopkins Hospital Bulletin, vol. xxi.,No. 237, December, 1910. Cushny and Edmunds: Paroxysmal Irregularity of the Heart and Auricular Fibrillation. Amer. Jour. Med. Sci., January, 1906. Fairbrother, H. C: A Remedy for Paroxysmal Tachycardia. Jour. Am. Med. Asso., 1909, kii., 300. Fredericq, Leon: La Pulsation du Cceur du Chien. Archives Internationales de Physiologie, July, 1906. Fulton, Judson, and Norris: Congenital Heart-block Occurri-g in a Father and Two Children. Am. Jour. Med. Sci., September, 1910. Gibson, G. A.: Bradycardia. Edin. Med. Jour., July, 1905. Griffith T. W.: Remarks on Two Cases of Heart-block. Heart, February, 1912. Hering, H. E.: TJeber den Pulsus pseudoalternans. Prager medic Wochensch, 1902, Bd., xxvii. Hewlett, A. W.: Heart-block in the Ventricular Walls. Archives of Int. Med., September, 1908. Jolly and Ritchie: Auricular Flutter and Fibrillation. Heart, May, 1911. James, W. B.: A Clinical Study of Some Arrhythmias of the Heart. Am. Jour. Med. Sci., October, 190S. Kraus and Nicolai: TJeber die funktionelle Solidaritat dor beiden Herzhiilften. Deutsche med. Wochensch., 1908, xxxiv., 1-5. Kussmaul: TJeber schwielige Mediastino-pericarditis und den paradoxen Puis. Berliner klin. Wochensch., 1873, No. 37. Laslett, E. E.: Syncopal Attacks Associated with Prolonged Arrest of the Whole Heart. Quar. Jour, of Med., July, 1909. Minkowski, O.: Die Registrierung der Herzbewegungen am linken Vorhof. Deutsche med. Wochensch., 1906, xxxii., 1248. Neuburger and Edinger: Einseitiger fast totaler Mangel des Cerebellums, Varix Oblongata?, Herztod durch Accessorius- reizung. Berliner klin. Wochensch., 1S9S, xxxv., 69-72 and 100-103. Riegel: TJeber extrapericardiale Verwachsungen. Berliner klin. Wochensch., 1S77, Xo. 45. Rihl, .:J TJeber atrioventrikulare Tachycardie beim Menschen. Deutsche med. Wochensch., 1907, xxxiii., 632-634. Schmoll, E. : Ataxia of the Heart Muscle. Am. Jour. Med. Sci., November, 1908. Stengel and Pepper: Heart-block with an Indication of Genuine Hemisystole Am. Jour. Med. Sci., October, 1910. Windle, J. D.: Observations on Pulsus Alternans. Heart, November, 1910. Young and Hewlett: The Normal Pulsations within the Esopha- gus. Jour, of Med. Research, vol. xvi., No. 3, July, 1907. 633 Arrow-Head Hot Springs REFERENCE HANDBOOK OF THE MEDICAL SCIENCES -San Bernardino County, Arrow-head Hot Springs. - California. Post-office. — Arrow-head Springs. Access. — By electric car from San Bernardino, six miles distant to the south. The trolley line is part of the extensive system covering southern California owned by the Southern Pacific System. San Bernar- dino is reached by the Salt Lake, the Southern Pacific, and the Atchison, Topeka, and Santa Fe Railroads. The springs and lakes are situated on the side of the Sierra Madre range. Thcs,. springs burst from the mountain slope of the Sierra Madre, 2,000 feet above the level of the sea. and 1,000 feet above the foot of the mountain. A bench- like mesa, containing 100 acres, projects at this point from the mountain, and is bounded on the east and on the west by two enormous canons. Down the deep ravine or canon on the east comes a mountain stream of water as cold as ice, while in the canon on the west flows a stream formed by the boiling spring so hot that it fills the air with steam and sulphurous gas. The springs here were known to the Indians long be- fore the settlement of the country by whites. On the face of the mountain back of the hotel is the figure of an arrow-head 1,360 feet long and 4~>0 feet wide, believed to have been executed by the aborigines. The figure gives its name to the resort, and so perfect is its contour and so elevated its situation that it can be seen from almost every part of the valley, and stands as a prominent landmark for miles around. The tent cottages are an attractive feature. The Arrowhead Hotel is located near the springs, on the plateau of land between the two canons. The hotel built in mission style is spacious, with broad verandas, superb 200 foot foyer and lobby, with great fixed stone fire places here and there. The bedrooms are large and cool. The hotel is provided with elevators, electric lights, shower baths, and every modern comfort. The Arrow-head estate, hotel, bath house, grounds and surroundings have been laid out and designed for a "Kurort," a great natural sana- torium. The grounds of the hotel cover 1,800 acres, and include the great Cold Water Canyon up into the heart of the mountains to the line of the Govern- ment Timber Reserve and a long reach of the beautiful Waterman Canyon up which an excellent carriage road leads to the summit. Arrow-head is on a fine highway system for automobiles. The meteorological conditions are similar to those usually prevalent in Southern California, the weather being, as a rule, clear, balmy, and bright. The winter season is most favorable for visiting the springs. These are 37 in number, the aggregate flow of water being equal to 10 miner's inches. Following is an analysis: The water shows a very high temperature, 202° F. The analysis bears some resemblance to that of the Carlsbad springs. The water is soft, clear, and pleasant to drink. The springs owe their chief repu- tation, however, to the beneficial effects of the water when used for bathing purposes. It is employed in the form of vapor, hot mineral water, and mud baths. Two of the most interesting features at Arrow-head are these wonderful mud baths and the natural steam room. The diseases and morbid conditions most susceptible to the beneficial influences of the Arrow- head waters are: Rheumatism, especially the chronic form; gout and the uric acid and lithemic group; dyspepsia and many chronic digestive disorders both gastric and intestinal; congestions and cir- rhoses of the liver, incipient gall-stone formation; the early stages of heart disease; incipient Bright'.-, disease and acute nephritis, and disturbances of the bladder and urinary and prostatic disorders; dia- betes; skin affections; neurasthenia, neuralgias and many forms of neuritis, as well as asthma, "colds", and bronchial affections are generally benefited; relief from pain, stiffness and incoordination, is often afforded in paralysis and paresis together with locomo- tor ataxia and scleroses. The springs offer many advantages for rest and enjoyment not only for in- valids, but for those in good health Emma E. Walker. Arrow=poisons. — The use of poison to increase the destructive effect of the arrow is probably as old as the use of the arrow itself. In the Book of Job (vi., 4) the poison is spoken of as inseparable from the arrow: "For the arrows of the Almighty are within me, the poison whereof drinketh up my spirit. 1 ' That the poisoning of arrows was a practice of the ancients is shown by our word toxic, which is derived from to&kos, relating to the bow, to&k6v cf>apfia.K6i>. meaning arrow-poison. The manliness of the fighting men of the middle ages led them to regard the use of poison for their arrows and spears as unworthy of a knight, much as the dumdum or soft-headed bullet is con- demned by the moderns, but among savage races it is still the accepted means of insuring victory in war or the chase. Poisons derived from the three kingdoms, animal, vegetable, and mineral, are used, but for the most part they are of vegetable origin. Of the mineral poisons, arsenic and antimony are the most common. The animal poisons are derived from the venom of snakes, scorpions, and centipedes and from poisonous fish. Among some of the tribes of American Indiana it was the custom to stick the liver of a buffalo or other large animal full of arrows and leave it to rot ANALYSIS OF ARROW-HEAD WATERS Grains Per Gallon By PROF. GILBERT E. BAILEY. Tem- pera- ture Sod- ium chlo- rid Sod- ium car- bon- ate Sod- ium sul- phate Sod- ium bor- ate Potas- sium sul- phate Potas- sium chlo- ride Cal- cium car- bon- ate Mag- nesium car- bonate Mag- nesium sul- phate Silica Lithia Hy- dro- gen sul- phide Iron Total Penyugal Hoi Spring. Wa terman H o t Springs. Graniti! Hot Spring. . 202° 200° 100° ISO" 7.070 6.104 6.607 5.269 2.733 1 244 1.045 3.224 2 . 243 2 903 42.650 33.215 34 . 6S7 90 Q03 0.887 4 007 1 594 2.395 i !.;7 4.246 3.521 4.211 3 nss 0.403 0.210 0.151 0.531 0.169 0.629 5.S06 4. 70S 5.301 4.240 0.911 1 . 758 Tr:ice Trace Trace Trace 0.491 0.140 0.128 0.134 l',7 2D.5 .',2.675 55 78S 47.062 1 471 1 022 n n?n l sis 8 303 ) 75J O 367 1) 128 O 7v>4 Trace * ''old Water Arrow-head Canyon. t Cold Water Canyon. g:u niir.HKxci: handbook of the medical sciences Arrow-poisons i a damp place. The Apaches are said to have | the beads of rattlesnakes with fragments <>f i '- liver ami when the mass had become putrid the beads were dipped in it and dried slowly. By ome tribes the heads of veni us snakes were I. a and the ashes moistened with water, the mil so formed being smeared over the lame points row heads. The toxic effect of such a prepara- ion was probably more imaginary than real, unless here was some other substance added, the nature [ which was not revealed. In most cases, indeed, iparation of the poison was a secret process DOWH only to the medicine men and chiefs, the lanipulations witnessed by the public being ex- in nature and designed to impress the lultitude while concealing the actual methods em- Comparatively few of the vegetable arrow-poisons Asia, Africa. .South America, and Australasia ave been analyzed or indeed even identified with ertituds. In most cases an extract is used, the ource being kept among the secrets of the medicine nen or chiefs, and revealed least of all to the strange hite man. In many cases there is a mixture of -itraets from several plants which still further es the difficulty of identification. Xeverthe- e number of natural orders of plants from uembers of which arrow-poisons are known to have ieen made is considerable and the number of genera .irge. The natural orders best known in this con- icction are Apocynaceae, and Loganiaceae, and ^preventatives of each are used in widely separated egions of the world. The Apocynaceae are repre- ented by three principal genera, Acocanthera, species .mi varieties of which are used throughout Africa .nd in the Fast Indies, Strophanthus and Adenium, ihich are also used extensively in various parts of \frica. The Loganiaceae, which comprise various of Stryehnos including those which furnish •urare, represent all the arrow-poisons of the Western lemisphere and also are used extensively in the East and Malay and are of considerable significance :: Africa. Other natural orders represented in force ire the Euphorbiaceae, which furnish a number of the ninor poison plants of Africa, the Urticaceae. which urnish species of the Antiaris much used in the East indies and Mala}-, while the Ranunculaceae are ■epresented in the Himalayas by Aconitum, and the Leguminosse by Erylhrophlaum in Africa and Denis in Asia. It is not uncommon to find com- ins of poisons from two natural orders or genera. To go a little more thoroughly into the and species, at least four species of Acocan- hera are the main sources of special kinds of poison, ivhile Strophanthus is represented by six, Adenium >y two, and Euphorbia and Stryehnos each by a large number. Antiaris and most of the other toxiferous jenera are represented apparently b}' a single It must of course be borne in mind that these plants ire only the ultimate sources of the chief poisonous sub- dances. The presence of other ingredients and the technique of preparation enter extensively into the individuality of the commercial (so to speak) articles. The best known among the latter are waba or ouabaio which is obtained from one species of Acocanthera and used extensively in Eastern Africa. The poison known as fra fra, used in the Gold Coast is also be- lieved to be derived from a member of the same g-'nus, while in the North East and in Southern Africa other species are used for the same purpose. The mode of preparation is inspissation of a decoction of the wood, and the active toxic principle is a gluco- side which is a cardiac poison. Other ingredients are added to this extract. It is affirmed that waba used utow poison will kill a man in a few minutes. Kombi, a poison obtained from different species of Strophanthus is much used in Central and Western Africa and is far less toxic than i fra fra. i. decoction is made of the strophai apo- rated and mixed with various ingredients. The ti action is that of strophanthus, arresting the heart in systole in fifteen or more mi mite-. /•;. huja i- a poison pn pared from the sap of species of Adenium which exudes through the action of heat. This Bap is very 10US and is wound upon wooden bobbins. I'n- like mosl of the arrow poisons it is a pure extract, and is used just as prepared. It is an intense cardiac poison like the Others enumerated and is used both in German Wesl Africa and in Somaliland. The Pygmy Arrow Poison so-called, is a mixture of extract of Erythrophlanim judiciale and strychnine and is powerful enough to kill elephants. The M Arrow Po I by a single Central African people is of unknown composition, a moderately virulent cardiac poison. L used to some extent in Herman I -last Africa, is also of unknown composition. It is perhaps a mixture of species of Acocanthera and Euphorbia. The arrow-poisons used in Asia are limited very largely to the Malay Peninsula and Fast Indies. They are used to some extent, however, in Hindoostan and the Philippines. A poison known by a variety of native names, one of which is upas, and another poison dajaksch, both consist of or contain the dried sap of ri's toxiearia. These poisons are — sometimes at least — mixed with a species of Stryehnos and other ingredients. The active principle of the sap is a glucoside which is a cardiac poison, the action of which resembles that of digitalis. The word upas or ipoh, with some qualification, is also used for arrow- poison prepared from various species of Stryehnos alone. Some of these poisons as they actually occur should greatly resemble in composition and action the South American woorara, or curare. They are used in Malacia and Borneo, and to some extent in Hindoo- stan. The principal arrow poison used in the latter country contains aconite; but although it is used very extensively throughout the northern part of the Empire, and is even known in China and Japan, authorities have little to say about it. It is no doubt complex and secret in its composition. It has re- cently been claimed that at least one arrow-poison in India (that used by the Abors) contains no aconite but some other substance which benumbs the tongue. According to Windsor (British Medical Journal, Jan. 6, 1912) the active principle Is from the croton oilplant (not the seed). In the Philippines one arrow- poison is in use by the Negritos. It is said to be pre- pared from a species of Rabelaisia and to be a cardiac poison. The arrow-poison used in Australasia is a mixture of animal, vegetable, and mineral matter and little is known or said of it. While arrow-poisons have been and are used extensively by the South American aborigines they are almost all of one character. Known as teoorara or curare they are obtained from various species of Stryehnos (see Curare). A few less virulent poisons are used to some extent in South and Central America. Authorities give sections on the treatment of arrow- poisoning, but this appears to be largely founded on a priori considerations. The rapidity with which some of these poisons kill, and the mixture of animal and vegetable poisons, the former comprising such substances as snake venom, and cadaveric and sep- tic poisons make antidoting difficult. Despite the fact that some of these poisons already contain strychnine it is advised to inject the alkaloid to antagonize the cardiac failure. Aside from the gen- eral management demanded by any poison wound it is apparently the custom to apply permanganate of potash in 3 per cent, solution locally. This oxidizes and destroys some of the toxic material, including of course all venoms. Edward Preble. G35 Arrow-poisons REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Literature. The number of journal articles on individual arrow-poisons is too great to be given here, and moreover many of the observations have been made by untrained observers and add little to the knowl- edge of the subject. The reader may consult with advantage "Die Pfeilgifte " by L. Lewin, Berlin, 1894. The subject is also very well treated in Geissler-Moeller's Real Enzyklopiidie der gesamten Pharmazie, 1904-1912, and in Castellani and Chalmer's Manual of Tropical Medicine, 1910, both of which have been con- sulted in the preparation of this article. Arrowroot. — Arroivroot Starch; Maranta Starch. The starch obtained from Maranta arundinacea L. (fain. Marantacece). The genus Maranta contains some fifteen species, natives of tropical America. They are perennial herbs, with tuberous or thickened, starch-laden, scaly rhizomes, and leafy, often branched stems. The arrowroot plant is extensively cultivated in nearly all tropical countries. A large amount of arrowroot is now produced in Southern Asia. The Indian plant differs somewhat from the American, but is considered as only a variety of it. The early medicinal application of arrowroot among the aborigines appears to have been as a remedy for the wounds of their arrows, to which it owes its name. It was both given internally and applied as a poultice on the injured part. It was also used as a food. Accounts of its cultivation in the West Indies date back about 150 years, since which time it has been an article of general commerce. Arrowroot is prepared in essentially the same way as other starches, namely, by washing -it out of the cellular tissue. The yield is about ten per cent, of the fresh rhizome. That of the West Indies, generally called Bermuda arrowroot, is regarded as the best. It is a beautifully white, lumpy powder, without odor or taste. Rubbed between the fingers it gives a slight crackling sound, or rather, feeling, for the sensation is conveyed more through the fingers than the ears. Its other properties are simply those of starch in general, to which the reader is referred. When the antiphlogistic treatment of diseases was more in vogue than at present, arrowroot took quite an important place in the dietary of the sick. It was also extensively used as an ingredient of foods for infants. For neither of these purposes is it to be much recommended. As a food, it has scarcely any advantages over the cheaper indigenous starches now so admirably prepared. Florida arrowroot is a starch prepared from the large fleshy stem of Zamia integrifolia Jacq. H. H. Rusbt. Arrowroot, Indian. See Curcuma. Arsacetin. — Trade name of sodium acetyl-arsan- ilate, C,H,O.NH.C„H 4 AsO(ONa)(OH)+5H_,0._ It is derived from sodium arsanilate by the substitution of a hydrogen atom in the amino group by an acetyl radical, and may also be prepared by adding acetyl- arsanilic acid to a warm concentrated soda solution. It occurs in the form of fine light aeicular crystals, without odor or taste, soluble in ten parts of cold water and about three parts of boiling water. It is employed in the treatment of trypanosomiasis, for which purpose some prefer it to atoxyl, than which it is said to be less toxic and more efficacious. Good results are also claimed in the treatment of syphilis, given hypodermically in doses of gr. i. (0.06) on two successive days in each week for ten weeks. In try- panosomiasis (sleeping sickness) it has been given in doses of gr. i.-v. (0.06-0.3) hypodermically. Arsanilates. — These are organic arsenic eom- pounds, salts of arsanilic acid, the latter being derived iron) arsenic acid by the substitution of one of the hydroxyls (HO) by an aniline radical. The arsan- ilates are employed in the treatment of various pro- tozoal diseases, such as trypanosomiasis, syphilis and yaws. The most commonly employed arsan- ilates are arsacetin (sodium acetyl arsanilate) and atoxyl or soamin (sodium arsanilate). T. L. S. Arsenic. — Arsenic is a member of the group which also contains nitrogen phosphorus, and antimony. It occurs free, but is more often found in combination as a sulphide. Its symbol is As, valence. III or V, and its atomic weight is 75. It possesses a steel-grav color and a pronounced metallic lustre. General Medicinal Properties op the Com- pounds of Arsenic. — The predominant feature of the action of arsenical preparations is intense irri- tation. Locally applied in fairly concentrated form to a denuded surface the irritation is so severe as to excite the extreme of reaction, namely, gangrenous inflammation; the part sloughs, strangulated by con- gestion and inflammation. Arsenic is thus indirectly, and, because indirectly, is slowly, painfully, and dangerously caustic. When arsenic is used to cau- terize, there is also a risk of absorption of enough of the mineral to produce constitutional poisoning, a risk greater when the application is weak than v. it is strong, since in the latter case congestion is developed early, whereby absorption is impeded. When arsenic is taken internally, gastrointestinal irritation is easily produced, a result which, in acute arsenical poisoning, constitutes the most prominent feature of the derangement. Apart from a tendency to irritate, arsenic is fairly antiseptic, and in the, higher organisms, such as man, has an action upon the nervous system. In arsenical poisoning nervous symptoms are prominent, and, therapeutically, much of the benefit of arsenicals hinges upon the allaying of nervous derangements. For the purposes for which arsenic is used in medi- cine the remedy has to be administered continuously for days, weeks, or months. In this medication the rule is so to adjust the dosage as not to develop con- stitutional disturbance. The initial symptoms of overdosage with arsenic are, first, an irritation of the conjunctiva, showing itself in suffusion and smarting of the eye, and edema of the lower lid; and secondly, an irritation of the stomach, shown by failure of appetite and soreness and sensation of weight at the epigastrium. In some persons the gastric symptoms precede the conjunctival. The two sets of sympti should be watched for in arsenical medication, and the dosage diminished or temporarily discontinued until their abatement, which speedily follows the withdrawal of the poison. Arsenic is valuable therapeutically on account of: Improvement of Nutrition. — Even in the healthy carefully graduated dosage with arsenic tends to im- prove general nutrition, the individual fattening, the skin being specially rosy and smooth, or, in animals the fur sleek and glossy, and the bones thick and dense. In the case of the so called arsenic eaters of Styria, the women are said to indulge for the beautifying of their complexion, and the men for an improvement of wind and increased physical endurance which they claim to derive from the use of arsenic. This habit of regu- lar consumption of arsenic among certain of the work- ing class in Styria seems now established as a fact by competent and reliable testimony. Arsenous acid is the preparation commonly used, and the daily allowance has been known to reach five and even tea grains. But attempts in other countries to acquire the tolerance of the poison which the Styrian peas- antry show commonly end in disaster. The prop- erty of arsenic to modify nutrition is utilized prin- cipally in the following diseases: Progressive per- nicious anemia: In this affection, where iron is so 63G - REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arsenic lotoriously futile, arsenic has in many cases proved ,i great benefit, patients even recovering fully under tsuse. Scaly skin diseases: In skin diseases arsenic more or less used, bu( experience shows that it is •!, more likely to be of benefit in affections of the pidermis than in those involving the corium. Psori- , a typical disease of the runner kind, and in its reatment arsenic is a standard remedy. At the icginning of an arsenical course the symptoms often utter an exacerbation, but this commonly subsides B few davs. The medicine should not be pre- oribed during the inflammatory stage <>f a skin dis- nit when used should bo persisted in for weeks en months after apparent cure. Under all imstances, the remedial action is slow. o\ of Veuroses. — The property of arsenic o affect nerve functions, seen in the nervous phe- omena that attend arsenical poisoning, shows itself lerapeutically in a tendency to abate pain, spasm, m.| undue reflex irritability. The property is util- .1 most especially in the following conditions: irritability: In idiopathic dyspeptic irri- abUity of the stomach, or in the irritability at tend ins; lie chronic gastritis of drunkards, or ulcer or cancer if the stomach, arsenic is often of considerable benefit, md is especially efficacious when the nervous dis- urbance is disproportionately great. Neuroses of he respiratory organs: Some asthmatics find a ■rtain amount of temporary relief from arsenic, a vlief more likely to be obtained in the pure neurotic orni of the disease than when the symptoms are econdary to bronchitis, emphysema, or disease of he hi': rt. Yet the nerve irritation in coryza may ie relieved, and, according to Ringer, paroxysmal rig is often promptly averted by the remedy, tcept when caused by true hay fever the result of lie inhalation of pollen. In chorea arsenic is prob- ibly the most generally serviceable of medicines. Simple uncomplicated cases recover under the use if the remedy more frequently than not. Neuralgia tlso sometimes yields to arsenic, more particularly ivhen the attacks show a regular periodicity of onset; D other words, when the affection is very likely of nalarial origin. Other neuroses also, such as angina lectoris, and even epilepsy, have occasionally been rented by arsenic, and isolated cases have been •eported in which benefit has been claimed from the medication. Besides the foregoing, arsenic has been used in a _'reat variety of diseases on the general principle of being an "alterative," with alleged success in many uses. The Preparations of Arsenic Used in Medi- cine. — The arsenical compounds used in medicine ire the trioxide (arsenous acid), triiodide, and the dts, potassium arsenite and sodium arsenate. Arsenic Trioxide, As.,03. This well known com- pound is official in the U. S. P. as Arseni Trioxidum. This is the preparation known also as white arsenic, or, in common parlance, simply arsenic. Arsenic trioxide occurs either as an opaque white pow'der, or in irregular masses of two varieties: one amor- phous, transparent and colorless, like glass; the other crystalline, opaque or white, resembling porcelain. Frequently the same piece has an opaque, white, outer crust enclosing the glassy variety within. Con- taot with moist air gradually changes the glassy into the white, opaque variety. Both are odorless and tasteless. In cold water both varieties dissolve very slowly, the degree of solubility varying according to conditions and time, the glassy variety requiring about 30, the porcelain-like about 100 parts of water at 25° C. (77° F.). Both are slowly but completely soluble in fifteen parts of boiling water. In alcohol arsenic trioxide is but sparingly soluble, but it is soluble in about five parts of glycerin. Oil of turpen- tine dissolves only the glassy variety. Both varieties are freely soluble in hydrochloric acid, and in volu- tions of alkali hydroxides and carbonates. (U. S. P.) Arsenic trioxide is obtained by sublimation, by roast- ing ores containing arsenic, and is subsequently purified by resubumation. tor medical use the mineral is pulverized, appearing then as a very fine, white, smooth powder, In this condition it is easily adulterated, but the fraud can readily be detected by submitting the sample to sublimation, when the arsenic trioxide will till disappear by volatilization, and the impurities be declared by a non-volat tie residue. Arsenic trioxide possesses all the physiological properties of arsenicals, a- set forth above. It does nni act upon the sound skin, but upon a mucous membrane or denuded surface produces violent irrita- tion. Taken internally it is capable of sufficient absorption to produce the constitutional effects of arsenic, therapeutic or toxic, and so may be used as a medicine, in doses of gr. ,,\ T (0.002) three limes a day, generally given in pill. But it is not an eligible preparation for internal use, because of the local irritation it is apt to set up. Externally it has been employed to destroy the tissues of cancer or lupus, applied in ointment or paste. For such pur- pose the arsenic trioxide is mixed with from four to eight times its weight of inert matter, such as oint- ment or a paste made of some indifferent powder mixed with mucilage. Such arsenical ointment or paste is then applied to the tissue to be destroyed, the point being observed, if the part be covered by skin, first to remove the epithelium by blistering. The application is to continue for from twelve to twenty-four hours. Weak arsenical mixtures are more dangerous than strong, because of the greater likelihood of constitutional poisoning. Even strong applications, if at all extensive, are risky, and at best the destruction of tissue by arsenic is a slow, uncertain, and very painful process, not to be com- mended. Most of the numberless caustic pastes of quack "cancer doctors" are preparations of arsenic trioxide. The only preparation of arsenic trioxide official in the U. S. P. is what is entitled Liquor Acidi Arsenosi, Solution of Arsenous Acid. This is a one- per-cent. solution of the arsenical in water slightly acidulated with hydrochloric acid. The preparation is of the same strength as Fowler's solution (see below), and is given in doses of njt iii. (0.2) three times a day, largely diluted with water. Arsenic Triiodide, Asl 3 . — This compound is official in the U. S. P. as Arseni Iodidum, Arsenic Iodide. It is "an orange-red, inodorous, crystalline powder, stable when protected from direct sunlight and kept in a cool place. Soluble, with partial decomposition, in about twelve parts of water, and in about twenty- eight parts of alcohol at 25° C. (77° F.); completely soluble in chloroform, carbon disulphide, or ether. No loss of iodine occurs when arsenous iodide is heated upon a water bath, but at higher temperatures it completely volatilizes. When warmed with a few drops of nitric acid, brown vapors of nitrous oxide are evolved, followed by violet vapors of iodine. The aqueous solution has a yellow color, is neutral to litmus paper, and upon standing gradually decom- poses into arsenous and hydriodic acids." (U. S. P.) This iodide has been given internally as an arseni- cal in doses of gr. ^ (0.005), and used externally on malignant growths in a one-per-cent. ointment; but its principal purpose among medicines is to furnish the pharmacist with the arsenical ingredient of the official preparation, Liquor Arseni et Hydrargyri lodidi, Solution of Arsenous and Mercuric Iodides, commonly known as Donovan's Solution. This is an aqueous solution of one per cent, each of arsenous iodide and red mercuric iodide. It is a pale yellow fluid, slightly astringent in flavor, and precipitating with alkalies, silver solutions, and solutions of alka- loidal salts. It is used as a composite "alterative" 637 Arsenic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES internal medicine, its reputation being principally in the line of .scaly skin disease, syphilitic or idio- pathic, and in rheumatic affections. Dose, m> iss. (0.1). Potassium Arsenite. — An arsenite of potassium is official in the U. S. P. only in the solution entitled Liquor Polassii Arsenitis, Solution of Potassium Arsenite, better known by the common name of Fowler's Solution. This solution is made by boiling one part of arsenic trioxide and two of potassium bicarbonate in water until chemical union is effected, then bringing the solution to the standard strength of one per cent, of arsenic trioxide, and adding three parts of compound tincture of lavender. This latter addition is to give the preparation sufficient taste and color to prevent its being mistaken for simple water. Fowler's solution is clear, and tastes only of lavender. It responds to the usual tests for arsenic. Physio- logically it acts the same as would a solution of arsenic trioxide of like strength. It was originally prepared in imitation of a famous remedy known as "tasteless ague drop," and is the most convenient and commonly used arsenical for internal administra- tion. The average dose is gtt. iii.-v. (0.2-0.3), well diluted with water, to be taken, like all arsenicals, after eating, and repeated two or three times a day. Sodium Arsenate, Na,HAs0 4 +7H,0. — The salt is official under title Sodii Arsenas, Sodium Arsenate. It occurs in "colorless, transparent, monoclinic prisms, odorless, and having a mild, alkaline taste; it should be tasted with great caution as the salt is very poisonous. Efflorescent in dry air, and some- what deliquescent in moist air. Soluble in 1.2 parts of water at 25° C. (77° F.)., and very soluble in boiling water; very sparingly soluble in cold, but nearly insoluble in boiling alcohol. When gently heated, the salt loses five molecules of water (28.8 per cent.), and is converted into a white powder. At 148° C. (298.4° F.)> the rest of the water of crystallization is lost, the salt fuses, and at a red heat is converted into pyroarsenate." (U. S. P.) Sodium arsenate has the usual properties of the arsenicals, but is a little milder than potassium arsenite. ' It is generally prescribed in the official Liquor Sodii Arsenatis, Solution of Sodium Arsenate, which is simply a one-per-cent. aqueous solution of the salt. This solution may be given in the same dose and manner as Fowler's solution. Exsiccated Sodium Arsenate, Na 2 HAsO„ containing not less than ninety-eight per cent, of the pure anhy- drous salt, is official under the name Sodii Arsenas Exsiccatus. "An amorphous, white powder; odor- less, and having a mildly alkaline taste; it should be tasted with great caution, as the salt is very poisonous. Permanent in dry air. Soluble in three parts of water at 25° C. (77° F.), and very soluble in boiling water; very sparingly soluble in cold, but nearly insoluble in boiling alcohol. When heated to 150° C. (302° F.), the salt should not lose weight; at red heat it is con- verted into pyroarsenate. It imparts an intense vellow color to a non-luminous flame." (U. S. P.) Dose, gr. ^ (0.003). R. J. E. Scott. Arteries, Anatomy. — See articles on the various regions — Abdomen, Arm and Forearm, Leg, Neck, etc. Arteries, Anomalies of. — Arteries are subject to frequent variations of size, origin, and distribution. Some of these are so common that it is difficult to decide what is the normal condition. Many anoma- lous arteries are merely a persistence of an early fetal condition, others are reversions to forms of distribu- tion which are natural in the various species of the lower animals, while some are due to an abnormal enlargement or diminution of vessels which naturally exist. I propose in the present article chiefly to describe those anomalies which are important surgi- cally — that is, those which exist in parts liable to dis- ease which necessitate a surgical operation for theii cure or relief. However interesting would be a con- sideration of anomalies of arteries from a morpholog- ical point of view to pure anatomists, I fear the sub- ject is not of sufficient interest to the general profession to justify me in devoting much space to it here. Aorta. — This vessel is subject to many variations. It may vary in length and position. The summit ot the arch has been seen as high as the top of the sternum and as low as the fifth dorsal vertebra. The distance to which it reaches on the spine before dividing into the two common iliacs also varies, the point of division being occasionally as low as the fifth, and as high as the third, or even the second lumbar vertebra. The aorta has been seen consisting of two closely united tubes, in part or the whole of its course, due to a per- sistence of the original double aorta of early fetal life (Fig. 354). The aorta is sometimes very tortuous, of large size, and displaced to one side, especially in old people, but this condition is due a /^T\ more to patho- logical changes than to congen- ital malforma- tion. The m a i n trunks of the aorta and pul- monary artery are (4, Fig. 354) both derived from the arte- rial bulb of the fetal heart, "and are liable to variations which may be traced to devia- tions from the natural mode of their septal di- vision and of th eir union with the left or right ventricles of the heart respectively" (Quain's "An- atomy"). These variations are generally associated with malformations of the heart, and often with pa- tency of the ductus arteriosus. The aortic or pul- monary trunk may be almost obliterated, or the two trunks may communicate freely with each other, ow- ing to the failure of complete septal division; again, their origins may be transposed, the pulmonary an arising from the left ventricle and the aorta from the right. A very rare anomaly has been reported where the pulmonary artery and aorta form one stem which arises from a simple heart like that seen in fishes. A few cases are reported in which the de- scending aorta arose from the pulmonary artery and gave off the left subclavian, the left ventricle giving off only the innominate and left carotid. Most of these varieties are incompatible with life, and are fully described in works on pathological anatomy. Varieties of the Aortic Arch. — The various anomalies of the aortic arch depend on the mode of develop- ment of the fourth and fifth fetal branchial arches. In man and nearly all mammalia the arch is a left one, produced l\\ i lie per- \ tence of i he fourl h left branchial arch (Fig. 355). In birds the permanent aorta i formed from the right fourth branchial arch; and in reptiles both the right and left fourth branchial arches are persistent. In cases in which there is transposition of the heart, and also, of course, of the arch of the aorta, the aorta is a right one, instead of the usual left, 5' Fig. 354. — Diagrammatic Outlines of Heart and First Arterial Vessels of the Embryo, as Seen from the Abdominal Surface. 4. Aortic bulb; 5, 5, the primitive aortic arches and their continuation as the descending aorta. These vessels are separate in their whole extent in .1 (36 to 38 mm. in thickness), but at a later period, as shown more fully in C, have coal- esced into one tube in a part of the dorsal region. In B, below upper 5. the second aortic arch is formed and farther down the dotted lines indicate the position of thesuo- ceeding arches, numbering five in all. (Quain's "Anatomy.") 638 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries, Anomalies Of md this is owing to the persistence of the right fourth branchial arch, as in birds. The pulmonary artery in hese cases i> also transposed and is formed from the ighl fifth arch in place of from the left. .Many of these cases have ct\l\ <^«, /I/ * been reported and have been diag- nosed during life, the. direct ion of I he apex; of the heart being toward the right, the apex beat being felt on the right side between the fifth and sixth ribs. A very good specimen of this anomaly is to be seen in the museum of the Pennsylva- nia Hospital in Philadelphia. Occasionally the aortic arch has been observed coin- Iil itely double dig. 356), as in reptiles, due to the persis- tence of both right and left aortic roots (a, a', Fig. 355) and the fourth bran- chial arches of both sides. The double aorta embraces the trachea and esoph- agus, and unites below to form a single trunk on the left side of the spinal column, as in early fetal life (B, Fig. 355. — Diagram of the Fetal Aortic , Showing Their Transformation the Permanent Vessels of the Mam- mal. (After Rathke.) The permanent are represented by the deep tg, the pulmonary arteries lighter, tporary primitive arehes in out- iv. A, P, Primitive aortic stem, [ into A, aortic arch, P, pul - nary artery; a, right aortic root: a' left i< root: A' , descending aorta; 1, 2, 3, 1, 5, primitive vascular arches; pn, pn' , ml left pneumogastric nerves; '', ,-'. right and left vertebrals; s, s', right Etnd left subclavians; ce, external caro- . ri', internal carotids. (From Quoin's "Anatomy.") Fig. 354). The aorta may pass to the right of the trachea and esophagus instead of to the left, and this without the transposition of the heart mentioned above. If we study the fetal conditions the explanation of this anomaly is easy. It is a persistence of the right fourth branchial arch and aortic root instead of the left i Fig. 355). In these cases the re- current laryngeal nerve of the left side hooks around the subclavian, and that of the right around the arch of the aorta. In some of the cases of right arch that have been observed the left subclavian arose from the back part of the descending aorta, passed be- hind the trachea, I reached its usual position in the neck between the alene muscles. In 9 of this kind tlie first part of the subclavian being absent, owing to the non-develop- ment, or rather obliteration, of the fourth left ular arch, the inferior laryngeal nerve does not hook around it, but goes directly, to the larynx, Fig. 356. — Example of a Double Ascending Aorta, from the Arch of Which Arise Six Branches — Two Subclavian and Four Carotid Arteries. (After Malacarne.) I'm,. 357. - T h e Right Subclavian Ar- tery Displaced or Proceeding from the Right Aortic Root. a, right aortic root mg as thesub- claviau artery; a', left aortic root; P, pulmonary artery. (Q u a in 's "Anat- omy.") and the vertebral artery may arise directly from the arch. Variations in Number and I' f the Bran of the Arch of the Aorta.- These variations are very numerous; 1 shall mention only the most common and important. The branches of the aortic arch may be gi-, en off from a single I riink, which forms what is called the an- terior aorta. This arrangement is seen in the horse. 'I he common- e t abnormal arrangement of the branches is thai where the left carotid arises from the innom- inate; 1 1 1 1 1 3 only two bfanchi are given off from the arch, the left subclavian and the innominate* This is the usual distribution in most of the carnivora. There may lie two Denominates given oil' from the arch, each dividing into a carotid and subclavian, as in the bat. Three branches is the normal number arising from the arch in man, apes, and a few other animals. i Iccasionally we see three branches A, A', ascending and ar i s j n g from the arch in a different descending portion from the norma l. We may ; have the two subclavians arising separately, and the two carotids arising from a common stem be- tween them. This is the normal disposition in some cetacea. Some- times all four vessels arise sepa- rately from the arch. Again, the left vertebral may arise from the arch, while the other branches preserve the normal arrangement, or there may be five branches given off separately, viz., the two subclavians, two carotids, and left vertebral. As many as six branches have been seen to come off from the aortic arch. This occurs when, in addition to the above-mentioned five branches the right vertebral is also given off. A curious anomaly, and one which is interesting from its rarity and manner of development, is that form of arch, where the right and left carotids and left sub- clavian arises separately from the arch, and the right subclavian arises from the back part of the descending aorta, passes behind the trachea and esophagus and ascending portion of the arch, and reaches its normal place between the scalene muscles (Fig. 357). In this case the right inferior laryngeal nerve, instead of hooking round the subclavian, passes directly to the larynx. The subclavian here represents the persistent right aortic root, and the right fourth branchial arch is obliterated (see Fig. 355). Some years ago I met with a curious anomaly having some- what this character. I looked upon it as a double sub- clavian. The right subcla- vian was given off as usual from the innominate, but was joined in the second part of its course, between the scalene muscles, by a small branch which arose from the back part of the descending aorta. I considered this a case of persistence of the fourth right vascular arch, and also of the right aortic root (Fig. 358). (lor a complete de- scription of the very many varieties of the arch of the aorta, see Turner on " Varieties of the Arch of the Aorta," in Brit, and For. M , d.-Chir. I\< r.,lS62; Henle's " Anatomy, " vol. iii.; Hyrtl; and Professor Struthers.) Fig. 358.— Right Aortic Root Persisting as a Small Branch Which Connects theDescending Aort;, with the Subclavian. May be regarded as an example of double subclavian. 039 Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Innominate, or Brachiocephalic. — This artery occasionally varies as to the point of its division. In some cases it divides above the sternoclavicular artic- ulation, and in others considerably below it. When there is a high division, there is danger of its being wounded in tracheotomy, especially in those cases in which the artery inclines to the median line. In cases of ligature, however, the operation would be much facilitated by a high division, and rendered much more difficult by a low one. The thyroidea ima or middle thyroid (Fig. 359) is not infrequently given off from the innominate, and as- cends to its destination in front of the trachea. When present it would complicate the operations of trache- otomy and excision of the thyroid gland. In observa- tions by myself on 250 subjects, I found that this artery occurred twelve times or once in 20.83 cases. Richard Quain, in his valuable work on the arteries, found it nine times in 291 subjects, or once in 32.33. It is sometimes of large size, dividing into two branches, one of which goes to each lobe of the thyroid gland. This artery sometimes arises from the right common carotid, and rarely from the arch of the aorta between the left carotid and innominate. Common Carotid Arteries. — These vessels may vary in their origin and place of division. The right carotid occasionally arises directly from the arch of the aorta either alone or with the left carotid. In the latter case the artery, to reach its usual position on the right side, crosses the trachea above the upper border of the sternum, a fact worth remembering in connection with the operation of tracheotomy. It may arise above or be- low the sterno-clavicular articulation, according as the innominate is longer or shorter than usual. The left carotid varies more frequently in origin than the right, as it is derived from the innominate in about one case in nine. It may also arise from the arch in common with the right carotid. Place of Division. — The common carotid often varies as to its place of division. The normal divid- ing point is opposite the upper border of the thyroid cartilage, but it sometimes divides as high up as the hyoid bone, and as low down as the cricoid cartilage. Morgagni reports a case in which it divided at the root of the neck. Cases are recorded in which it did not divide at all, one or other of its main branches being absent. I have occasionally seen this artery give off the superior thyroid and ascending pharyngeal before its division, and also a small laryngeal. I also once saw the left carotid giving off the left vertebral. External Carotid and Its Branches. — As men- tioned above, the origin of the external carotid varies considerably. It has in rare cases been noticed arising from the innominate, and even from the arch of the aorta itself. Absence of this artery has been met with, the branches arising at varying intervals from a common trunk, representing both internal and external carotids. The artery sometimes passes between the digastric muscle, and stylohyoid. I have in one case seen it pass up to the parotid gland superficial to both the posterior belly of the digastric and the stylohyoid, instead of behind them. The origin of the branches varies considerably; they 640 T.I.— Fig. 359. — Showing a Middle Thyroid Artery (T.I.) Arising from the Innominate and Run- ning up the Front of the Trachea to Supply the Thyroid Gland. (From R. Quain, sligh tly altered.) may be crowded together at the commencement ol the vessel, or at a point higher up. Sometimes they arise from the main trunk at nearly regular intervals and occasionally we find several branches arising from a single stem. Accessory arteries may arise from _ the external carotid, such as the accessory superior thyroid and accessory ascending pharyngeal. The sternomastoid, which usually arises from the occipital, occasionally arises from the main trunk, and when this occurs the hypoglossal nerve hook- around this small branch instead of around the oci i pital. In consequence of the lower origin of the sternomastoid, the nerve in such eases passes lower down the neck before crossing the vessels to reach the hyoglossus muscle. Superior Thyroid. — This vessel may be very small or absent, its place being taken by the artery of the opposite side and the inferior thyroid of the same side. It sometimes arises from the common carotid. The cricothyroid may be of considerable size, and its superior laryngeal branch may arise from the main trunk, or pierce the thyroid cartilage instead of the thyrohyoid membrane, as is the case in many mam- mals. Mr. Walsham ("St. Bartholomew's Hosp. Rep.," 1880) has several times met with a large branch from the superior thyroid crossing the trachea between the cricoid cartilage and isthmus of the thyroid. He once wounded it in performing tracheotomy. Lingual. — This artery often arises in common with the facial, and occasionally with the superior thyroid. Instead of passing beneath the hyoglossus muscle it has been seen to pierce it. In some rare cases it has been absent, and its place has been taken by a branch from the internal maxil- lary. Its place has been taken also by a branch from the facial, the submental. Its sublingual branch is occasionally derived from the facial. The hyoid branch is often wanting, and in such cases the hyoid branch of the superior thyroid takes its place. The lingual sometimes gives off the submental and ascending palatine artery. In one case of opera- tion on the dead subject, the writer could not find the artery in the usual place, but it was found coming off from the superior thyroid passing up to the median line of the neck on the thyrohyoid muscle. It crossed the hyoid bone internal to the lesser cornu, pierced the hyoglossus muscle, and thence onward its course was normal (Annals of Surgery, vol. ix. 1889, p. 33). Facial. — This artery is very variable in size and also in extent. When the facial is deficient its place is taken by the transverse facial, internal maxillary. or ophthalmic, most frequently the first mentioned. Occipital. — This artery usually arises opposite the facial, but its place of origin may be above or below this point. Sometimes it is derived from the internal carotid or the ascending cervical branch of the inferior thyroid. It occasionally passes to its destination superficial to the trachelomastoid mus- cle, or it may pierce the sternomastoid and splenius capitis muscles. R. Quain mentions a case in which it passed superficial to the sternomastoid muscle. It not infrequently gives off the posterior auricular and ascending pharyngeal. Posterior Auricular. — Often a branch of the occip- ital; sometimes of small size, ending in the sterno- mastoid muscle. Ascending Pharyngeal. — Varies greatly in its place of origin; may arsie from the internal carotid, occipital, or a linguo-facial branch. It is occasionally double. Superficial. — This vessel is very often tortuous, especially in the aged. The transverse facial is occasionally of large size, and takes the place of the facial. It is sometimes double. Internal Maxillary. — This artery frequently arises in common with the temporal. R. Quain has observed REFERENCE HANDBOOK 01 THE MEDICAL SCIENCES Arteries. Anomalies of i, two instances arising from the facial, "fr vhich it coursed upward, to pass beneath the ramus ,f the maxillary bone in the usual situation." It very frequently (in about 1.5 per cent.) is cov- iv, I by the external pterygoid muscle, instead of vine superficially to that muscle, it sometimes orates the external pterygoid, and rarely the niernal. It may replace the facial by a 1. ranch i the posterior dental, buccal, or infraorbital [nternal Carotid and Its Branches. — This irlcry in the neck is occasionally very tortuous. It I known to be absent, its place being taken the artery of the opposite side or by a branch the internal maxillary. It is sometimes very I, smaller than the vertebral (Hyrtl). The tiding pharyngeal, occipital, lingual, or trans- facial may arise from the internal carotid. c communicating branch has been seen going this artery, while in the cavernous sinus, to the ia-ilar artery; in such a case the posterior communi- lating branch is wanting. The posterior cerebral ifrequently comes off from one of its branches, terior communicating. halmic Branch. — This has been seen to come >1T from the middle meningeal artery. Occasionally the middle meningeal conies off from the ophthalmic. I he ophthalmic may, by its nasal branch, supply a iency in the facial. In fifteen per cent, of cases rosses beneath instead of over the optic nerve. I; has been seen to go through the sphenoidal fissure. Cerebral Arteries. — The anterior cerebral of one side is often much larger than that of the other. In some es (lie two anterior cerebral arteries are united into a common trunk, like the basilar. The nor communicating artery is sometimes double; I have once seen it treble. It is often very short. The posterior cerebral may arise from the internal carotid by a large posterior communicating. It has seen by Hyrtl to give off the middle cerebral. The posterior communicating artery occasionally comes off from the middle cerebral instead of from ternal carotid. Subclavian. — The varieties of origin of this artery have ahead}' been mentioned in the account of the anomalies of the arch of the aorta and innominate artery. It is generally given off from the innominate on the right side, opposite the sternoclavicular articu- lation, but occasionally the innominate reaches nearly as high up as the cricoid cartilage before it divides, and in these cases the artery would be at an unusually high level. The highest part of the artery is the second portion, and it is normally about 1.2 to 2.7 em. (one-half to three-quarters of an inch) above the clavicle, with the shoulder depressed, but not infre- itly it may be below, or on a level with, the clavicle, and sometimes, especially on the right side, it may be placed as high as 3.7 cm. (one inch and a half) above the level of the clavicle. It may, in those rare cases in which a cervical rib is attached to the seventh cervical vertebra, pass over this rib in place of the first dorsal, and be raised fully two inches above the clavicle. I have seen this occur once in two hundred and fifty subjects examined. In the living, when this condition exists, it may be, and has been, mistaken for aneurysm. Sir James Paget has diagnosed this anomaly four times during life. It is obvious that the height to which the ar- tery reaches is important in cases in which ligature is necessary. I have seen in one case in which there was an incomplete left first rib the artery pass over the second rib. On the right side there was also a rudimentary first rib completed by fibrous tissue. There was a deep groove in this rib, in which rested the artery; before complete dissection this was taken for a cervical rib. The cases for which ligature is undertaken are chiefly those of aneurysm of the Vol. I.— 41 axillary artery, in which, in con i qui nee of the con- dition of the pan , the shoulder is elevated. If the artery should be al an unusually low level, or even just behind I he clavicle, tin- operation, a- may be conceived, would be rendered extremel] difficult. The third part of the artery in thin people with small muscles is very superficial, bill in stout, muscu- lar individuals it is verj deeplj placed. Dupuytren says: "The third part of the subclavian lies near the skin in those who are thin and have -hauler and Long necks, with lean and pendent shoulders; it i-. on the contrary, deeply hidden in persons who have short, thick necks and muscular shoulders." Occasionally the subclavian artery pierces the sca- lenus anticua instead of going behind it, and more rarely passes entirely in front of the muscle; of the first variety I have seen five cases in I wo hundred and fifty subjects (three on the left and two on the right side); of the second, in the same number of subjects examined, I have seen only one example. The vein may pass with the artery behind the anterior scalenus, and in very rare cases their normal positions may be reversed. The trapezius may cover the third part of the subclavian, or it may have in front of it the omohyoid muscle. These condi- tions, however, will be more fully described under Muscles, A nomalii .-. of. Variations of Branches.— It is important, surgically speaking, that the position of the various branches given off from the subclavian should be considered. The branches given off from the first part do not, as a rule, vary much in their arrangement, but several may be transferred to the second or third portions. The left vertebral may arise from the arch of the aorta instead of from the first part of the left subclavian, and the branches of the thyroid axis may be given off separately. The first part of the right subclavian, having been occasionally ligated, it is necessary to known at what distance from the innominate the branches arise. In the majority of cases this is from 1.25 can. (half an inch) to 2.4 cm. (one inch) (R. Quain); but it often exceeds this, and is frequently 2.4 em. (one inch) to 3.S em. (one inch and three-quarters). In a small minority of cases the distance is under 1.2 cm. (half an inch). In the second portion of the artery, one branch, as a rule, is given off, the superior intercostal; occasionally no branches are seen here, and again, not infrequently, there are two or three. The third portion, in a little more than half the cases, gives off no branch, in a little less than half, one branch, occasionally two, and in very rare cases three and four. Vertebral Artery. — Origin: The right vertebral, in those rare cases in which the right subclavian arises from the arch of the aorta, is given off from the com- mon carotid of the right side. The right vertebral has been seen coming from the arch. Mr. A. M. Paterson (Jour. Anat. and Phys., April, 1SS4) records a case of right vertebral arising from the aortic arch beyond the left subclavian, and reaching the vertebra- arterial canal by passing behind the trachea and esophagus; in fact, following exactly the course of the subclavian when it arises from the back part of the arch, as figured above. Mr. Paterson regards this anomaly as a persistence of the right aortic root, with obliteration of the connection between the subclavian and vertebral arteries where they cross. The left vertebral not infrequently is given off from the arch of the aorta, generally between the left carotid and left subclavian. I have seen this arrange- ment twelve times in two hundred and fifty subjects. I have once seen it come off from the left common carotid. The vertebral has been seen with two, and even three roots (R. Quain). Course: This vessel may fail to enter the trans- verse process of the sixth cervical vertebra, but 641 Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES continue up the neck between the inferior thyroid artery and vein to enter the transverse process of any of the vertebrae from the fifth to the second. It is not uncommon for it to enter the transverse process of the fourth or fifth vertebra, but it is only very occasionally that it passes up as high as the third and second before entering the foramen. Again, it may enter the transverse process of the seventh cervical vertebra, instead of the sixth. Size: The left vertebral is frequently much larger than the right, especially in those cases in which it is given off directly from the arch of the aorta. Some- times the vertebral is nearly as large as the common carotid, at other times as small as the ascending cervical branch of the inferior thyroid. Branches: The vertebral may, as a very rare occur- rence, give off the inferior thyroid or superior inter- costal artery. I have seen two examples of the first variety occurring on both sides of same subject. Its inferior cerebellar branch is frequently absent on one side. The thyroidea ima has been observed in rare cases to come off from the right subclavian. The upper end of the vertebral artery occasionally divides into two branches, which unite a little higher up, thus forming a loop through which pass filaments of the hypoglossal nerve. I have seen this anomaly in two instances. Thyroid Axis. — This trunk occasionally arises beyond the scalenus anticus muscle (according to R. Quain twice in two hundred and seventy-three cases). It not infrequently gives origin to the inter- nal mammary. It is sometimes absent, its branches being given off separately from the subclavian. Inferior Thyroid. — This artery frequently arises as an independent branch from the subclavian. It has been seen to arise from the common carotid, and 6.S Fig. 360. — Inferior Thyroid Artery Dividing into Two Branches, one of which (a) passes in front of the carotid sheath, the other (b) behind it. (Anderson: Jour. Anal, and Phys., vol. xiv.) not infrequently from the vertebral. It varies con- siderably in size, and when small its place is taken by the superior thyroid. In cases of enlarged thyroid gland (bronchocele) it is often nearly as large as the carotid. Two inferior thyroids have been found on the same side, one having the normal course beneath 642 the carotid artery, and the other reaching its destina- tion by passing superficially to that vessel (Fig. 360). Its branches of division are closely connected with the recurrent laryngeal nerve, which may pass beneath or above them, a point to be borne in mind in extirpation of the thyroid gland. The inferior thyroid may be wanting altogether, its place being supplied by an enlarged superior thyroid of the same side. The ascending cervical branch of the inferior thyroid may be derived directly from the subclavian or one of its branches. It is occasionally of large size, and may take the place of the occipital. Suprascapular. — This artery is usually derived from the thyroid axis, but not infrequently has a different origin. It is often given off directly from the subclavian. It may be given off from the internal mammary. I have several times seen it derived from the subscapular and also from the axillary. It is often very small. Transverse Cervical. — This artery when given off from the thyroid axis divides into two terminal branches, viz., the superficial cervical and posterior scapular. Very often the superficial cervical only is given off from the thyroid axis, the posterior scapular coming off as a separate branch from the second or third part of the subclavian, rarely from the first part. It is well, when ligaturing the third part of the sub- clavian, to remember that the posterior scapular comes off from it about once in every three cases. When the posterior scapular artery is given off from the third part of the subclavian I have not infre- quently seen it pierce the fibers of the scalenus medius muscle, and occasionally go between the cords of the brachial plexus. The posterior scapular artery may be given off from the axillary, or it may end near the scapula in a small branch, its place being supplied by branches from the suprascapular. The superficial cervical may come off from the sub- clavian as a separate branch, the posterior scapular alone being derived from the thyroid axis. When the posterior scapular is a branch of the third part of the subclavian it often gives off a large branch to supply the trapezius, which represents the greater part of the superficial cervical, the latter artery in such cases being very small ^r absent. The transverse cervical artery is occasionally given off from the subclavian as a separate branch. Internal Mammary. — This is a large and very regu- lar branch of the subclavian, generally arising from the lower part opposite the vertebral. It may arise from the thyroid axis, axillary, or innominate, or even from the arch of the aorta. It may also form a common trunk with either of the scapular arteries, and be given off from the second or third part of the subclavian. Hyrtl describes a case in which the trunk of this artery crossed in front of the fifth right costal cartilage, coming out of the thorax through the fourth interspace and re-entering it by the fifth. In one case the author saw the phrenic nerve pierced by this artery. A branch is sometimes given off from the upper part of the internal mammary, called by Henle the A. mammaria interna, lateralis, which crosses the inner surface of the upper four to six ribs and inter- costal spaces at right angles, about midway between the spine and sternum, anastomosing in its course downward and outward with the intercostal arteries. In penetrating wounds of the thorax, fractured ribs, and other injuries, this lateral branch might be wounded and give rise to dangerous hemorrhage. It might also be wounded in the operation for evacu- ating an empyema. Superior Intercostal. — Sometimes arises from the thyroid axis or vertebral. I have seen it arise from the internal mammary. It may be of considerable size, and may supply three or four intercostal spaces. It in some cases passes between the neck of the first REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries, Anomalies of i second rib and the corresponding transverse process f the dorsal vertebra, li is very rarely absent. Deep Cervical. — This artery is generally a branch i the preceding, but occasionally is derived directly ,,m the subclavian, in the proportion of 1 in 20 tbiects (R. Quain). In rare cases it arises from po terior scapular and interna] mammary. It is ,,t infrequently of small size, its place being taken , the deep cervical branch of the occipital, a branch : the inferior thyroid, the ascending cervical or a osterior cervical branch of the transverse cervical Henle). li may pass between the transverse processes of the ith and sixth cervical, first and second dorsal, or nil and third dorsal instead of between the th cervical transverse process and first rib. Ih, re is sometimes an accessory branch accom- anyingit. Axillary Artery. — The most important anomaly f this vessel is its early division into two trunks, one f which may give off all or most of the branches, or lay be a high origin of the radial, ulnar, or even the iterosseous artery (Fig. 361). When one of the runks gives off all or most of the branches it is nearly surrounded by the brachial plexus of nerves id embraced by the two heads of the median. The ranches given off from this common stem may vary. I have seen it give origin to the acromial thoracic, long thoracic, anterior and posterior circumflex, subscapu- lar, and one or both of the profunda arteries of the arm; the anterior and posterior scapular with the subscapular arteries not infre- quently come from a common stem. This arrangement of the branches of the axillary occurs normally in many animals, e.g. the lemur, tapir, peccary, dolphin, etc., and much resembles that which takes place in the lower extremity, viz., the common femoral divid- ing into a superficial and a deep branch, the deep giving off all the branches, and the superficial going down the extremity branch- less. According to Richard Quain, this variation occurred twenty-eight times in 506 arms examined. I have met with it only fifteen times in 500 irma in which the arrangement of the axillary was ibserved. Quain gives the proportion of cases in vhich one of the arteries of the forearm is derived rom the axillary as 23 in 506; Gruber, 21 in 1,200. ( have found this condition to exist twelve times in 500 arms examined. The radial is the branch most frequently given iff in these cases, next the ulnar, and very rarely the nterosseous. I have only once seen the interos- seous arise from the axillary. An aberrant artery is occasionally found arising ;rom the axillary; it generally courses down the arm alongside the brachial, which it joins near the elbow. Sometimes this aberrant vessel joins the radial, Fig. 361.— Origin of Radial (R) rom the Axillary (B). (After teeves.) ulnar, or interosseous artery near the writ. Our remarkable case Came Under my observation sonic; years ago in which this aberrant artery passed down the arm superficial to the la cia, in tic- forearm fol- lowed the course of the 1 lian nerve, coininiinieated with the radial by several transverse branches, and finally ended by taking the place of the superficial volar, completing the superficial palmar arch il ig. 362). The most constant branch of the axillary is the long thoracic or external mammary; this, or a repre- sentative of it, is nearly always seen running along tin' lower border of the iieetoralis minor muscle; it, however, not infrequently arises from the thoracic axis and occasionally from the subscapular. Then- may also be an accessory external mammary. The subscapular and circumflex branches frequently arise together. The dorsalis scapula 1 , instead of being derived from the subscapular, may arise directly from the axillary. The posterior circumflex occasionally fails to enter the quadrilateral space (formed by the humerus, subscapulars muscle, long head of triceps, and teres major), but reaches the deltoid muscle by winding round the lower border of the tendons of the latissimus dorsi and teres major muscles. It not in- frequently arises from the superior profunda, and is sometimes double. In rare cases the internal mammary, posterior scapular, or suprascapular may arise from the axillary. Brachial Artery. — The varia- tions in the course, relations, and distribution of this artery are very- numerous and of special surgical interest. Course: The brachial artery some- times, accompanied by the median nerve, courses down the arm to the internal condyle of the humerus, and thence regains its normal position at the bend of the elbow, by passing forward under a fibrous or bony arch. This arch is formed, usually, partly by bone and partly by ligament; the bony process is called the supracon- dyloid and the fora- men, which is com- pleted by a ligair°nt from the tip of the process to the in- ternal condyle, the supracondyloid for- amen. In these cases it is usual to have a high origin of the pronator radii teres muscle from the supracondyloid process. This ar- rangement is said to be more common in dark races, and is the normal one in all the cat tribe and in monkeys, lemurs, and sloths. In these animals the foramen is nearly always completed by bone, and affords protection to the median nerve and artery during flexion of the fore-limb, and also affords them a more direct course to the fore-limb. In man the artery may occasionally take this course without there being present a supracondyloid process; there may be only a high origin of the teres muscle. 643 Fig. 362. — Example of an Aberrant Artery from Axillary, Going to Com- plete the Superficial Palmar Arch, Tak- ing the Place in the Hand of the Super- ficial Volar. Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Division: I have once soon the artery divide near its commencement into two branches which unite to form one trunk near the bend of the elbow, from which the ulnar and radial arteries are given off at the usual place (Fig. 363). In 4S1 arms examined by R. Quain a high division was found sixty-four times, a low division (that is, below usual place) only once. Gruber, in 1,200 arms examined, found a high division in 82. In 500 arms examined by myself, I found a high division in only 27, and in one case the brachial divided below the pronator teres. Adding to these the cases in which the division takes place in the axilla, in 4S1 arms examined by Quain two arteries existed in the arm in 9-4 cases, or 1 in about 5|. My statistics are quite different from the above, and I cannot account for the great diversity. The same class of people were examined, and they were of the same race. In 500 arms I found that two arteries existed in only 43 cases. This is made up as fol- lows: divi- sion of axil- lary, 12; di- vision of brachial, 27; aberrant arteries, 4 — total, 43, or 1 in 11.6 cases. W. Gruber, in 1,200 arms, found a high division in 103, or 1 in 11. (3, the same proportion exactly as in my own cases. The point of division is in most cases in the upper third of the arm. It is also seen in the mid- dle and lower thirds, but much Fin. 363. — Brachial Dividing High up, Reuniting at Elbow, and then almost Immediately Dividing into the Radial and Ulnar. V. Vas aberrans. (After Reeves.) Fig. 364.— High Or- igin of the Ulnar Ar- tery(U). Ab, aberrant artery; R, radial, giv- ing »ff the interos- seous arteries. less frequently. The artery which is given off thus prematurely is generally (three cases out of four) the radial; this vessel is most frequently to the ulnar side, and subsequently crosses to the radial. Next in fre- quency comes the ulnar, which often, in these cases, E asses superficially down the forearm and gives off no ranches, the interosseous coining from the radial 644 (Fig. 364). In rare cases the interosseous is the branch having the high origin (Fig. 365), and still more rarely it is a vas aberrans. Three branches have been seen in the arm, viz., the radial, the ulnar, and a vas aberrans. The position of the two branches in the arm when a high division occurs is of surgical importance. They are usually in the ordinary position of the brachial trunk and lie close together Fig. 365. — Anterior Interos- seous (I) Given off from the Brachial High up. (After Reeves.) Fig. 366.— Aberrant Ar tery (3), separating fron^ the brachial (1) at the mid- dle of the arm, passing with the median nerve (d) through the internal intei- muscular septum, and joining the regular ulnar (4) lower down. (Quain i but the radial, as mentioned above, often arises from the inner side, and, after accompanying the large vessel for some distance, crosses over it at the bend of the elbow. The ulnar artery, when having a high origin, may incline toward the internal condyle, this, however, occurs only when it nears the elbow. When there is a high division of the brachial the ulnar-interos- seous branch may pass through the supracondyloid foramen mentioned above, and under a high origin of the pronator teres. The aberrant arteries, which are given off occasion- ally, are long, slender arteries, which are derived from the brachial or axillary, and end by joining the radial most frequently and sometimes the ulnar ami interosseous. They are loop lines, so to speak, and in cases of ligature of the brachial their occasional occurrence must be borne in mind by the surgeon (Fig. 366). The two arteries in the arm are in sonic instances connected together by anastomosing trans- verse branches. These branches may number two or three, or even four. A median artery has been described as arising from the brachial and passing down over the muscles of the forearm and supplying the finger to which is distrib- uted the median nerve. The brachial artery may in some part of its course (more frequently near the elbow) be covered by a muscular slip. The median nerve sometimes passes behind instead of in front of the artery, especially REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries. Anomalies of ,, those cases in which the two heads embrace a ommoo trunk from which the axillary branches ,,. riven off. Superior Profunda. — This is occasionally derived i/.ni a trunk common to it and several of the axillary tranches, as mentioned above. It nol uncommonly arises with the circumflex, ami occasionally gives off the inferior profunda. Inferior Profunda. — This is often absent. It is frequently united with the superior pro- funda. A nastomotica M nana. — Frequently of small size; its place is sometimes taken by the inferior profunda. Radial Artery. — Origin: I have found that the radial has a high origin (Fig. 367) in one case in twenty-one, but Quain reports the high origin to occur as often as one in eight. Gruber in 440 arms examined found the radial had a high origin in twenty-six, or about one in seventeen cases. Course: The radial only very occasionally deviates from its usual course in the forearm. It has been found lying superficial to the fa-' ia of the forearm, and the semi- lunar fascia of the biceps. It in rare cases courses down the forearm on the surface of the supinator longus instead Fig. 367.— Dissection of Right Arm. Showing an ex- ample of high separation of the radial artery (3) from the brachial V2); a large median artery (10) is seen in forearm. (From Quain's "Anatomy," after Tiede- mann.J Fig. 368. — No Dis- tinct Superficial Arch. Large superficial volar supplying thumb and index finger with half middle finger, arid rest supplied by ulnar. (Reeves.) of along its inner border. It not infrequently is erficial to the tendons of the extensor muscles of the thumb. It is occasionally joined by a vas aber- rans. It may leave the front of the forearm near its middle, its place being taken by an enlarged superfi- cial volar. This would cause a weak wrist pulse. Size : It does not vary often in size. It is, however, sometimes much smaller than usual, its place being, to a considerable extent, taken by some other vessel, as the ulnar and anterior interosseous. The radial has been described as absent by some anatomists. Quain never saw a case of absence of this artery, but such a case is described by Professor t »i to, and 1 have seen one case. Branches. Radial recurrent: This ve ''I i ome times of large size, or it may eon i I of several small branches. Winn the radial has a high origin 1 1 >• - recurrent branch is given off from the ulnar-intero seous trunk. Superficial volar: Very often of small size, so small thai it terminates in the muscles of the thumb, and does not complete the superficial palmar arch. It is occasionally entirely absent. It may be of large size and furnish several digital branches (Fig. 'MW), and it nitty arise much higher than usual. I once saw it arise as high as the middle of the fore- arm, and it was quite as large as tint radial, from which it was derived; this is the normal arrangement in some monkeys. The first dorsal interosseous is, in s e cases, of large size, and may supply several digits and end by completing the superficial arch. The carpal and dorsal interosseous branches are |f,\ w|MJ\ \ often of very small size, j \ their place being taken by s^i'i A \ the perforating arteries. FlG. 369.- Abnormal Su- perficial Ulnar Artery (:i, 3'), Rising Higher than Usual from the Brachial. (Quain's "Anatomy," after R. Quain.) Fig. 370. — Dissection of Left Arm. Showing an en- larged median arterj (5) which replaces the radial [2) and ulnar (3) arteries in the supply of the palmar digital arteries to half the fingers. (From Quain's "Anatomy," after Tiedemanu.) Ulnar Artery. — Origin: Quain found that this artery deviated from the usual origin in our case in thirteen, Gruber one in twenty-nine, myself one in thirty-seven. Where the origin of the ulnar is unusual, it most ci im- monly arises from the brachial in the arm, and less commonly from the axillary. In one case out of five 645 Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES hundred I found it coming off from the brachial below the pronator radii teres. In this case there was, of course, a low division of the brachial. Course: In the forearm this artery is much more subject to variation than the radial. When it has a high origin it nearly always courses down the fore- arm superficial to the muscles, but beneath the fascia; but cases occasionally occur in which it is immedi- ately beneath the skin and superficial to the fascia (Fig. 369). When the ulnar is superficial, it, as a rule, gives off no branches in the forearm, these being given off from the radial — interosseous trunk — or the interosseous itself, which is invariably given off from the radial. The ulnar, in rare cases, has this superficial course when it arises in its usual situation. Interosseous Artery. — This artery, in rare cases, arises from the axillary or brachial artery (Fig. 364), and gives off the recurrent radial and ulnar arteries. The anterior and posterior interosseous may arise separately from the ulnar. Median Artery (Fig. 370). — This branch, which accompanies the median nerve, is ordinarily of small size, but occasionally it is developed into quite an important vessel. It is usually derived from the anterior interosseous, but sometimes from the ulnar, and, in rare cases, it has been found coming from the axillary or the brachial. It accompanies the median nerve and reaches the hand beneath the annular ligament, but, according to Tiedemann, sometimes passes over the ligament. It may complete the palmar arch, or be distributed as digital branches to certain of the fingers, generally those supplied by the median nerve, which it accompanies. In the cases which I have observed, the latter arrangement was the more frequent. I have occasionally seen this artery pierce the median nerve. Arteries of the Hand. — The arteries of the hand are subject to man}' variations. The superficial palmar arch is sometimes entirely wanting. It has been occasionally seen double. In Fig. 371. — Superficial Arch Formed Entirely by the Ulnar and Joining the Princeps Pollicis Artery. (Reeves.) Fig. 372.— Lars e Median Artery (Af), Taking the Place of the Radial in the Forma- tion of the Superfi- cial Arch and Giv- ing off Outer Digitals. (Reeves.) the majority of cases the superficial volar branch does not complete the arch, but it is completed often by a large branch from the radial, which emerges between the thumb and forefinger, and I have sometimes seen it completed by a large branch from the radial, which, after coursing over the back of the hand, emerges on the palm between the index and middle fingers. The arch is also often completed by a transverse branch, which comes from the muscles of the thumb and is derived from the princeps pollicis or radialis indicia branch of the radial (Fig. 371). A median artery may complete the arch (Fig. 372), or it may go to the digits on the radial side, and the 646 ulnar to the digits on the ulnar side, and no regular arch be formed. The superficial volar sometimes has this arrangement (Fig. 372). The superficial arch may be very small and some of the digital branches be wanting, or it may be very large, suppljing all the digital branches, both super- ficial and deep. The deep arch is occasionally formed by the ulnar. It is sometimes so deficient that the digital arteries are derived from the superficial arch. A large meta- carpal branch on the back of the hand may give off the digital branches. Abdominal Aorta. — According to R. Quain, in ten out of every thirteen bodies the division of the great artery took place within half an inch above or below the level of the iliac crest. Eckhard, Boinet, and Cruveilhier record cases of division as high up as the second lumbar. Two cases are on record (Quain, tenth ed.) of a large pulmonary branch which arose below the diaphragm, passed through the esophageal opening, and divided into two branches which sup- plied the lungs near their bases. Celiac Artery. — The branches of this artery may arise separately from the aorta. The phrenic arteries may be given off from it, and it may be connected with the superior mesenteric. Renal Arteries. — Now that the operation of nephrectomy has become so common, the variations of these arteries have been rendered important surgi- cally. Professor Macalister has reported (Journ. Anal, and Phys., vol. xvii.) most of the anomalies of the renal artery. The renal artery may be replaced by two, three, four, and even six branches. The origin of these arteries is very various; they are usually derived from the aorta, and are separated, at their origin, by a larger or smaller interval; the lowest may arise quite near the bifurcation of the aorta, and the highest just below the celiac axis. In some rare instances the renal artery has been described as arising from the common iliac, internal iliac, and middle sacral. The right and left renal arteries have been found coming from a common trunk; they may arise from the anterior or lateral part of the aorta. The suprarenal frequently gives off an upper renal, and it less fre- quently is derived from the upper lumbar, hepatic, and right colic. Frequently when the renal arteries come off from the aorta low down or the iliacs, the kidney on that side is misplaced; it is situated lower down than usual. opposite the bifurcation of the aorta and even between the two common iliacs. In such cases the hilum is usually placed on the anterior surface. The branches of the renal artery, instead of entering the hilum, may penetrate the kidney at its upper or lower end. It is not uncommon to see the normal artery entering the hilum, and two or three super- numerary branches piercing the upper and lower end of the gland. In two subjects I found that the kidney was supplied by two arteries arising from the aorta at some distance apart, one going to the extreme upper end, and the other to the extreme lower end of the kidney; no artery entered the hilum (Fig. 373). The vein and duct were normal. This variation I once met with while performing nephrectomy on the dead body. R. Quain met with a case of absence of the renal artery on one side. Multiple renal arteries occur normally in fishes, lizards, snakes, crocodiles, Fig. 373. — Abnormf., Right Renal Arteries. An Artery distributed to each extremity of the kidney! but none entering the hilum. REFERENCE HANDBOOK OF THE MKDK'AL S( II. N< i - Arteries, Anomalies (if I'm. 374- — Obturator Given off Internal 1 pigastric, and •sine to the Inside of the Crural Reach the Obturator ..Mien. (After Gray.) ,1 birds, and in man are due to a persistent early Dndition. Inferior Mesenteric. — It may be absent, its being given off from the superior mesenteric. SpBBMATIC Artery. — Sometimes double, not infre- iently derived from the renal. Three spermatic teries have been seen. Common Iliac Arteries. — The place of origin of ese arteries depends on the place of division of the dominal aorta. This may be as high as the upper border of the third, or as low as the loner border of the fifth lumbar ver- tebra. In three out of four eases the aorta di- vides opposite the lower border of the fourth lumbar. The common iliac ar- teries vary considerably in length. I once saw them only 1.8 cm. (three- fourths inch) long in a negress, and, in another case, 2.5 cm. (one inch). In the large majority of cases, according to R. Quain, the length varies oin 3.7 cm. (one inch and a half) to 7.5 cm. (three ches). The greatest length is about 10 cm. (four 1 a half inches). The right and left common iliacs differ in length ■ry often, the right, owing to the aorta dividing to ie" loft side of the spinal column, being often the tiger; but the left may be the longer, and in about rd of the cases they are of equal length | R. mitt i. When the left is longer than or equal to the right, is owing to the left artery descending to a lower vel than the right. The artery has been seen viding into internal and external iliacs as low down iliac fossa. The common iliac on one side has been reported by Cruveilhier and Walsham. In this case to aorta divided into three branches, two on the \ternal and internal iliac), as is seen in birds, id one on the left (common iliac). Surgically, these ariations are of great interest. Internal Iliac. — The place of division of this aries considerably; it may divide as low as ie margin of the sacro-sciatic foramen and as high - tlie upper margin of e sacrum. The point f division is of impor- irgieally; when ie trunk is short it is tore deeply placed in ie back part of the elvis, but when it is of itne length, then a part f the artery is likely to e above the pelvic cav- y, and therefore would e much more easily ■ached by the surgeon H. Quain). It ha- been Hind as short as 1.2 cm. half an inch), and as long as 8.2 cm. (three and a alf inches). The branches are given off from this artery very ariously. In many cases there is no division into nterior and posterior trunks. The artery occasion- lly gives off one, and sometimes two branches he- re it divides. The variations of most of the •ranches of this artery, being of no surgical impor- ance, will not be discussed here. Fig. 375.— TheObturatorGiven off from the Internal Epigastric and Passing to the Outside of the Ring. (After Gray.) Obturator. — According to li. Quain, the obtura- tor artery arises from the epigastric in one ca e in :;.;,, His conclusions are derived from observations in 36] cases. I have observed 500 cases (250 sub- ject i. and have found this abnormal arrangement much less frequently than Quain. I have found the obturator coming from the epigastric in only i Ca e in ni .",."> in 5011). Quain found the obturator derived from tlie external iliac in si\ ca i out of 361. I found it only three time- in 500 cases. Quain found tin- epigastric giving off the obturator twenty- three time, ,,n both sides. I found this arrangement eleven times. When the obturator arises from the epigastric or external iliac, it reaches tlie thyroid foramen ly arching either to tlie inner or to the outer side of the femoral ring. If it arches to the inner side of the femoral ring, along the edge of < limbernat 's ligament, then, in case of strangulated hernia requiring opera- tion, it would be in great danger of being wounded dig. 374); in fact, this accident has happened more than once. In only nine out of the fifty-eight cases in which the obturator proceeded from the epigastric and external iliac did I see the artery going to the inner side of the femoral ring. In the remaining forty- nine cases it either crossed it, in a few cases, or held a position well to the outer side in the majority (Fig. 375), so that in only about one case in fifty is there danger of wounding the obturator in the operation for strangulated hernia. The explanation of the origin of the obturator from the epigastric is simple enough. Normally, we have the pubic branch of the obturator anastomosing with the pubic branch of the epigastric; these vessels become enlarged, and the proper obturator branch of the internal iliac either remains undeveloped or becomes obliterated. In four cases I have seen the obturator, epigastric, and internal circumflex arise together from the external iliac, and once these same arteries were seen to arise by a common trunk from the common femoral 2 cm. below Poupart's ligament. In one case the epigastric and obturator arose together from the femoral, a little below Poupart's ligament. In some cases, in which the obturator arises from the epigastric, there is a small branch, representing the obturator, derived from the internal iliac. Interna! Pvdic Artery. — This vessel is occasionally of small size, and fails to supply all the usual branches; in s-uch an event these are given off from an accessory pudic. The branches furnished by the accessory artery are usually those branches which go to the cavernous body and dorsum of the penis, the ,. ., ... ,r ., course .uiaway oeiween in pudic itself ending as the Ischial Tuberosity and th artery of the bulb. In a Coccyx. (After Henle.) few instances the pudic ends as the superficial perineal, the other branches coming from the accessory vessel. The accessory pudic is, as a rule, given off from the deep pudic within the pelvis; it then passes alongside the bladder and prostate, and, after piercing the triangular ligament, supplies the dorsum of the penis and the cavernous body, and, perhaps, the bulb. It may be given off from the obturator in the pelvis, or from the epigastric. The pudic artery has been seen passing up to the perineum midway between the tuberosity of the ischium and the coccyx, and ending as the superficial perineal and artery of the bulb (Fig. 376). 647 Fig. 376. — Abnormal Inter- nal Pudic Artery, Which Has a (nurse Midway between the Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Artery of the Bulb. — Is sometimes of large size, placed farther back than usual, and ascends obliquely to the bulb; in such a case it would necessarily be wounded in the operation of lithotomy. It may arise from the accessory pudic; when this happens it would be placed well in front of the usual incision for lithotomy. The dorsal artery of the penis has in some cases been seen to arise from the obturator artery near the thy- roid foramen, from the external pudic of the femoral, Fig -Abnormal Origin of the Internal Circumflex Artery (I): K, epigastric artery; PF, profunda femoris. and from the deep femoral. In the first case it would be in danger of being wounded in lithotomy. The two arteries of the penis sometimes unite to form a single trunk, or are united by transverse branches. Mr. Spence has described a large prostatic artery which gained the perineal surface of the prostate without dividing into minute branches. Wounds of the prostatic arteries have led to fatal hemorrhage in cases of lateral lithotomy. The sciatic artery is sometimes replaced by a branch from the gluteal. In a few cases this artery has been seen of large size, taking the place of the femoral (see under Variations of Femoral). There is some- times a large comes nervi ischiatici artery. The gluteal artery has been reported as absent (Roberts), its place being taken by a large branch from the fem- oral, passing outward and backward to the gluteal region. External Iliac Arteries. — The length of these arteries varies according to the point at which the common iliacs bifurcate; they usually measure 7.50 cm. (three inches) to 10 cm. (four inches) in length. In those rare cases in which the main artery of the limb is a continuation of the sciatic, it is much reduced in size. Epigastric Artery. — May arise at a higher point than usual. R. Quain reports it in one case 6.4 cm. (two and a half inches) above Poupart's ligament. It arises from the femoral in about one case in twenty. The usual place of origin is close to or opposite Pou- part's ligament. It may, in rare cases, arise from the deep femoral. The origin of the obturator from the epigastric has already been noticed. In a few cases the epigastric has been seen coming from the obturator when that vessel is a branch of the internal iliac. I have, in four instances, seen the epigastric arise in common with the internal circumflex artery of the deep femoral. In three of the cases the common stem arose from the femoral 2 cm. below Poupart's ligament; in the fourth, 2 cm. above the ligament. 648 In the last-named case the internal circumflex passe, beneath Poupart's ligament in the same compart- ment of the femoral sheath as the artery, and con- tinued down the thigh about 5 cm., lying betweei the artery and vein; it ended, after giving off a largt branch to the adductor muscles, as the internal cir cumflex proper (Fig. 377). A similar anomaly ha: been observed by Mr. A. Thompson (Journal Anai and Phys., April, 1SS3), but in the cases describee by him the artery passed internal to the femoral vein and would, he thinks, have been wounded in tht operation for relieving strangulated femoral hernia A similar arrangement of vessels exists normally ii the American black bear. I have met with foui cases in which the obturator, epigastric, and interna circumflex arose by a common stem, two below Poupart's ligament and two above. Circumflex Iliac Artery. — The origin of this artery b sometimes from the femoral. It is occasionally double. again a single vessel. Sir Charles Bell, when liga- Femoral Artery. — The femoral artery has, in some rare cases, been found of small size, and termi- \i }''! FlG. 37S. — Posterior View of the Right Thigh. The ischiatie artery much en- larged, accompanying the sciatic nerve, and taking the place of the femoral ar- tery. (After Dubreuil.) Fig. 370. — Bell's Case of Double Femoral Artery, .showing HgatuN of one of the trunks and the aneurysmal below. (After Bell fr< itn London Medr ical Gazette.) nating near the knee joint. When such a condition exists, the main artery of the limb is furnished by a branch from the internal iliac, generally the sciatic (Fig. 37S), which is much enlarged, and accompanies the sciatic nerve to the popliteal space, whence the course of the artery is the same as if the distribution had been normal. This is the usual arrangement in birds. Cases have been reported in which the femoral divided into two portions, which united below to form kitfi:f.vt: haxdkook or tiik medical SCIENCES Arteries, Anomalies of urine tli' femoral for popliteal aneurysm, met with hi-c anomaly. Though t li<- ligation of the femoral lid not arrest the pulsation in the aneurysm, the recognized till after the death of the tatient, when it was found that the femoral was louble. and only one of its divisions had been liga- ured (London Sled, and Phys.Jour., vol. lvi., 1826 Fig. 379.) Tiedemann, Houston, Dubreuil, 1'vrroll. and Quain also report cases. Mr. 11. A. Kelly (American Journal of the Medical Sciences, lanuary, 1882) reports three cases (one of which i loubtful), met with in the dissecting rooms in Phila- Iclphia. In two of these cases the artery divided .■low the profunda, ami reunited just above the in the adductor magnus. The division has above the origin of the profunda. The two femorals, when this arrangement occurs, run down the thigh, side by side, in separate fibrous .lis. m> that in cutting down on one the other would not be seen. 1 have occasionally seen, in cases of high origin of the profunda, the latter artery quite as large as the rficial femoral, and running down the thigh parallel to it. beyond the apex of Scarpa's triangle. wch a case it would be difficult, in the living. listinguish between the vessels, should ligature of the femoral be necessary. As a rule, the profunda li - to the outer side. The appearance of the above- l cot dition in Scarpa's triangle is very similar OS cases figured as double femoral, and I im- agine that the cases of double femoral reported as seen in amputating the thigh are only cases of larg - profunda arteries, especially as the disposition of the vessels below- the amputated point is not described. The pro/undo, or deep femoral artery, may be given off from the inner side of the main trunk, or in some cases from the back part of the vessi I It may arise above Poupart's ligament, or as much as 10 cm. (four inches) below it. It not uncommonly - 1.2 cm. (half an inch) below the ligament. When it is given off low down, one or both circumflex arteries arise from the femoral. The deep femoral has been occasionally altogether wanting, its branches arising separately from the main artery. The external circumflex artery not infrequently arises directly from the common femoral. It may be represented by two branches, and even three. which arise from the femoral or profunda — I have seen it arise in common with the internal circumflex. The internal circumflex artery also frequently arises directly from the femoral. It occasionally arises in common with the deep epigastric, ami passes down to the thigh in the same sh ath as the femoral vessel. This variety I have described under the Epigastric. It may arise with the epigastric from the femoral artery before the profunda is given off, and in some cases might be injured in the operation for strangu- late. 1 femoral hernia. I have twice seen it arise with the obturator and epigastric from a common stem. Unusual branches are. in rare cases, given off from the femoral. I once saw the dorsal artery of tie penis given off from the common femoral, cross the thigh at right angles, and reach the dorsum of the penis by piercing the deeper scrotal tissue. A large saphenous artery has been found which accompanied the great saphenous vein. It may arise above or below the profunda, course down the thigh between the adductor magnus and internal vastus, and pierce the deep fascia of the thigh on the inner side of the knee joint, where it reaches the inter- nal saphenous vein and accompanies it to the internal malleolus. This arrangement is the normal one in the rabbit and in some other mammals. _ I once saw this branch, after reaching the inner side of the knee, wind round to the front of the joint, below the patella, and divide into a cutaneous branch and a branch which pierced the ligamentum patella? to supply the interior of the joint. Popliteal Ak i i ry. This artery is not Bubjecl '.> many variations. '1 he chief deviation from the normal disposition consists in a high division of its terminal branches. 1 saw this only twice in 2.~>0 subjects; in both, the artery divided immediately above the upper edge of the posterior ligament of the knee joint. In -'-'7 subjects Quain found a high division in 10. Portal reports a case of low division of the popliteal, the artery dividing about the middle of the leg into anterior an. I posterior til ial. In cases of high division, tic peroneal artery arises from the anterior tibial; tin- was the arrangement in one of my cases. The artery and vein, usually so con- stant in their relation, may, in rare cases, eh:; places. When there is a third head to the gastroc- nemius muscle it usually passes between the artery and the vein. Ward Collins has seen the popliteal artery dividing in the upper part of the popliteal branches which united again below after a separate course of two inches. Cases are reported (Otto) of branches from the popliteal proceeding upward along the semin em- branosus muscle, and ending in one of the perforating arteries of the profunda. Also an aberrant artery is described as being given off above the knee joint, and joining tin- popliteal before its division (Hyrtl). A small saphenous artery lias been seen which accom- panies the short saphenous vein behind the external malleolus and anastomoses with one of the tarsal branches (Hyrtl). The azygos artery may be given off from one of the articular arteries. I once saw a common trunk give off the two superior articular arteries and the azygos. One or other of the articular branches may be absent, their place being supplied by an enlargement of the remaining arteries. Posterior Tibial. — In cases of high division of the popliteal the tibial is larger than usual. It may be increased or diminished in size. When increased, it partly takes the place of the peroneal or anterior tibial, and when diminished, it may be reinforced by transverse branches from the peroneal near the ankle. The posterior tibial may be of very small size and end near the middle of the leg, its place being taken by a large peroneal artery which furnishes the plantar arteries. In a lesser degree of diminution of the posterior tibial, the anterior tibial, or rather its dor- salis pedis branch, furnishes the arteries which form the plantar arch and its branches. In these cases the external plantar artery ends near the accessorius muscle. I have several times seen a muscular slip (flexor accessorius), which arose from the lower end of the fibula, or more commonly from the tibia, cross the tibial vessels behind the internal malleolus. The nerve is occasionally placed to the inner side of the artery, at the lower part of the leg. Peroneal Artery. — This artery, as described above, may take the plaee of the posterior tibial, or it may be of small size, and its place be supplied by a branch of the posterior tibial. The anterior peroneal branch may be of large size, and may take the place of the lower part of the anterior tibial, furnishing the arter- ies supplying the dorsum of the foot. In cases of high division of the popliteal, the pero- neal artery generally arises from the anterior til ial. It also arises in the same way. occasionally, when no high division takes place. I have seen it furnish a large internal calcanean branch as well as an external. An accessory peroneal sometimes exists. The internal plantar artery is sometimes of very small size, ending in the flexor brevis pollicis muscle, or it may be of large size, and furnish digital branches to the great and second toes. The external plantar is occasionally very small, ending in the accessorius muscle; when such a condi- tion exists the dorsalis pedis artery furnishes the deep plantar arch and digital branches. I have several times seen this anomaly. The artery is occasionally of large size, and partly takes the place of the dorsalis 649 Arteries, Anomalies of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES pedis branch of the anterior tibial. The digital arteries of two toes, generally the second and third, not infrequently come from a common stem. The deep arch is, in rare cases, double. Anterior Tibial Artery. — In some cases this artery is given off from the posterior tibial in the middle of the leg. When there is a high division of the popliteal it may give off the peroneal, and may pass beneath the popliteus muscle. In the leg it may be subcu- taneous, its pulsations being easily felt under the skin. Velpeau reports a case in which this artery did not pierce the interosseous membrane, but passed to the front of the leg round the fibula with the musculo- cutaneous nerve. It may be altogether wanting, its place being supplied by perforating branches from the posterior tibial, or it may end in the muscles about the middle of the leg. When there is such a distribu- tion the deficiency is made up by an enlarged anterior peroneal or plantar artery. It not infrequently fails to furnish digital branches, which, in this event, come from the plantar arteries. The artery may be of larger size than usual, and may take the place of the Eeroneal artery in some eases, and of the plantar ranches of the posterior tibial in others; the dorsalis pedis branch being of very large size, as mentioned in the description of the varieties of the posterior tibial. The dorsalis pedis artery sometimes ends in the neigh- borhood of the cuneiform bone. The anterior tibial, in some rare cases, gives off an anterior tibial recurrent to the knee joint. Francis J. Shepherd. Arteries, Compression of. — Compression of arteries for the arrest and prevention of hemorrhage and for the cure of aneurysm is a very old procedure, and one which, although in many instances superseded by ligation, made safe by the introduction of antiseptic surgery, is still employed to a considerable extent, particularly in the prevention of hemorrhage. Com- pression of the carotids, thereby lessening the blood supply to the brain, has been recommended and prac- tised at different periods in the treatment of epileptic convulsions, maniacal excitement, congestive head- ache, and for the purpose of producing sleep. Corning, of New York, in 1882, strongly urged the advantages of this procedure and devised a special instrument for the compression of the carotids. Compression is accomplished either by means of the hand or by some mechanical device. Digital compression may be either direct or indirect, that is, in the wound or over the vessel of supply, and may be employed for the immediate arrest of existing hemor- rhage or for the prevention of hemorrhage during an operation. This means is occasionally still used in the treatment of aneurysm, but has largely been super- seded by the ligature, by the combined use of gold or silver wire and electricity, and more recently by Matas's excellent endoaneurysmorrhaphy. For the instant arrest of bleeding nothing is more readily and satisfactorily employed than the fingers, placed either directly in the wound or over the arterial trunk sup- plying it. The greatest disadvantage of the method is that it is impossible to keep it up for a great length of time without the help of a number of intelligent assis- tants. There are two ways of applying digital com- pression, one by pressing the vessel between the fingers and a bone, the other by compressing it between the forefinger and the thumb. The former method is more satisfactory, because it can be kept up for a much longer period of time. When a change of hands is made the fresh hand should always be placed above the point of former compression before the first hand is removed. Digital compression can much more readily be employed when a wound has been made, thus ex- posing the vessel, than when it is attempted with con- siderable tissue intervening between the finger and the vessel, as, for instance, in compression of the abdominal aorta. 650 Innumerable forms of compression apparatus have been invented for compressing blood-vessels, one of the oldest and most universally used being the tourni- quet of Petit (Fig. 120), which consists of two metal plates, connected by a spiral screw, whereby they may be separated, and a strap which buckles around the limb. In the use of this tourniquet many surgeons apply a roller bandage over the vessel to be com- pressed and buckle the strap over this. The separa- tion of the plates by the screw tightens the strap and increases the pressure. In order to prevent the strap from cutting the skin it is well to apply first a turn or Flo. 380. — Esmarch's Elastic Compressor. two of muslin bandage about the part. In an emer- gency, when a tourniquet cannot be had, a fillet may be employed by passing a handkerchief or piece of cloth or cord about the limb and then tightening it by twisting it with a piece of wooden stick. Only suf- ficient pressure should be made to arrest the bleeding or stop the pulse as too great pressure tends to pro- duce gangrene. The most generally used means of compression to-day is the Esmarch bandage and tube (Fig. 3S0). The bandage is an ordinary rubber roller applied from the tip of the extremity up to the p> where it is desired to place the tube, and its object is the saving of the blood in the extremity, in case of amputation, and the freeing of the limb of blood when any operation is to be done upon it. The tube is of rubber, flat, and about one inch wide. This is passed tightly about the limb and fastened by a hook at one end of the tube and a chain at the other. Certain precautions must be observed in the use of this form of compression. One is to move the pari as little as possible after the tube is applied, as tear- ing of the tightly bound down muscles may occur, and another is to see that each turn of the bandage and tube overlaps the preced- ing, else pinching of the skin occurs. When a limb is dis- eased, compression with the bandage is not to be made over the diseased area, but it is to be applied above and below it, or else it is not to be used at all, but the limb is simply to be elevated for a time, after which the tube alone is to be used. This method of elastic constriction has the great advantages of simplicity and cleanliness over other forms of mechan- ical compression. Other forms of compression apparatus are so constructed that the pressure is exerted over the main artery without constricting the surrounding tissue. These forms are specially advantageous in the treatment of aneurysm, for they are much less likely to cause gangrene, which is so apt to follow the prolonged use of the two forms of compression above described. Esmarch's elastic com- pressorium for the aorta and Skey's compressor (Fig. 381) illustrate this point. Wyeth, of New York, introduced a method of compressing the vessels of the thigh in hip-joir.t 3S1. — Skey's Arterial Compressor. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries, Compression of amputation (see Figs. 191, 192), which is a combina- h ,u of the older methods of Trendelenburg and Dieffenbach. It consists in passing through the muscular tissue and skin above the point of amputa- tion two long steel mattress needles, and then apply- ing above them the constricting band of Esmarch. I u~ recent years I have used direct digital compres- sion of the common iliac or the femoral in hip joint md high thigh amputations and prefer it to the Wyeth method. It must not be forgotten that all 'orms of compression, if kept up for a great length if time or if the pressure is too great, may be pro- ductive of destruction of tissue at the point of ap- ilication or of gangrene in parts below. Also it QUSt be remembered that after circular constriction if an extremity reactionary hemorrhage may occur, md hence it is necessary to tie all bleeding points h fore closure of the wound. Great improvement has been made in the tempo- rary control of large arterial trunks by mechanical compressors applied directly to the vessel. The rub- ber-covered clamp of Crile is one of the best. The compression to be put on the vessel is regulated by i set screw. This method is most useful but care should be taken to avoid too great pressure as injury jf the intima, with the resulting thrombosis, will -ccur. Matas and Halsted have done an enormous imount of experimental work in the gradual com- iression of the vessels by means of metal bands which -an be tightened by degrees. In all likelihood some method of this kind will ultimately prove sat- sfactory in arresting the circulation in cases of ineurysm involving vessels which cannot be ligated ir dealt with according to the Matas method of •ndoaneurysmorrhaphy. Fiq. 382. — Compression of the Aorta. (Dr. W. W. Keen.) Right hand closed, a little to the left ol the median line: knuckles 01 index finger just touching the upper border of the umbilicus; left hand feels patient's pulse (femoral) at brim of pelvis. Special Arteries. — The aorta cannot be com- pressed until it has passed through the diaphragm into the abdomen, and then only with difficulty, un- less the abdomen be opened. Compression of the abdominal aorta is resorted to as a means of pre- venting severe hemorrhage from its distributing branches or for the purpose of temporarily arresting Fio. 383 Compression of the Brachial. the circulation in them: for example, in a hip-joint amputation, or in an attempt to cure an aneurysm. It can be satisfactorily accomplished without abdom- inal section iii thin persons, but in those with thick abdominal walls it is i erj difficult of accomplishment. As to the precise mode of effecting the desired pressure, one may employ an Esmarch 's elastic compressor or that of Skey, the liitter which is shown in the illustra- tion (Fig. 381), or the hand of an assistant may be em- ployed (Fig. 382). All of t he e mel hod are open to objections: they may cause an injury to the overlying intestine — and this is more likely to happen when an apparatus is used — or the compression ma} - prove to be inefficient, as when the instrument is not properly applied, or when it slip-, or when the, assistant's hand moves to one side of the artery. The usual position for the compression pad or the hand is just below the umbilicus and a little to the left; but the pulsation of the vessel must be definitely felt before compression is applied, and after the ap- plication of compression no operation should be done until all pulsation has ceased in the vessels below. There will be less danger of injuring the intestinal canal if it be first emptied by means of a cathartic and an enema; and before ap- plying the pad, the bowels should be pushed to the right side of the abdomen by rolling the patient on that side. When the abdomen is opened compression of the aorta is rendered easier and safer; it may be accomplished with the fingers or with a specially de- vised clamp consisting of two blades, one of which fits into the other somewhat after the style of a lithotrite. Great care should be exercised in the use of such an instrument or an injury may be done to the vessel itself or its neighbors. Momburg in 1908 de- scribed a method of produc- ing ischemia of the lower half of the body by con- stricting the abdomen with several turns of a heavy elastic bandage; as a pre- liminary procedure, the blood in the lower extremi ties is forced out by apply- ing an Esmarch bandage. Although this method of compressing the abdominal aorta has been used a num- ber of times without detri- ment to the intestine it does not appear to be a per- fectly safe procedure and should not be lightly under- taken. The common iliac may be compressed through the ab- dominal wall, through the Fig. 384. — Compression of the rectum, or through an in- Femoral, cision in the abdominal wall. The last method, which enables one to use the fingers, is by far the most satisfactory of the three and the only one that has been practised with anything like good re- sults. It has become now one of the recognized means of preventing hemorrhage in hip-joint amputation, particularly in those cases in which, because of dis- eased anterior flap, the Wyeth pins cannot be used. Dr. Charles McBurney first employed this method of 651 Arteries, Compression of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES preventing hemorrhage in 1S94. Experience has shown that the common iliac can very readily be compressed with the fingers in the abdominal cavity without the exertion of much force and without increasing the dangers of the operation. Compression through the rectum by means of Davy's lever is not so safe or so satisfactory as are the other methods. External Iliac. — This vessel can be compressed with tin- fingers or with an instrument placed just above Poupart's ligament, midway between the symphysis pubis and the anterior superior spine of the ilium. Femoral. — The course of this vessel is covered by a line drawn from the point midway between the symphysis pubis and the anterior superior spine of the ilium to the adductor tubercle on the inner condyle of the femur, and can be compressed by the fingers (Fig. 3S4) or by the tourniquet anywhere throughout its course, the force being exerted tow aid the bone. The popliteal occupies the middle of the popliteal space; it can best be compressed against the femur in the upper part of its course. The posterior tibial can readily be compressed by the finger as it passes midway between the internal malleolus and the point of the heel. The anterior tibial lies between the tendons of the tibialis anticus and the extensor longus hallueis, and can best be compressed after it becomes the dorsalis pedis and passes under the annular ligament. The subclavian can be compressed, unless exposed by incision, only in its last one-third, where ii crosses the first rib. Pressure should be made with the thumb in the angle formed by the posterior border of the sternocleidomastoid and the clavicle, and should be directed downward, backward, and inward against the rib. The tip of the shoulder should be depressed. Axillary. — Compression of this vessel can be made only in the last part of its course, and is accomplished by making pressure from within outward against the upper part of the humerus. The brachial artery can very readily be compressed against the shaft of the humerus, the inner edge of the biceps being the guide to its situation. The radial can be compressed against the anterior surface of the lower end of the radius between the tendons of the supinator longus and the flexor carpi radialis. The ulnar artery can be compressed against the anterior surface of the ulna between the flexor carpi ulnaris and the flexor sublimis digitorum. The common carotid and the external carotid can be compressed with the fingers or by means of one of the instruments specially devised for the purpose. The anterior border of the sternocleidomastoid is the guide to the vessels, and the pressure should be directed backward and inward. The facial can be compressed with ease as it passes over the lower jaw just in front of the masseter muscle. The temporal may be controlled by making pressure on the zygomatic process just in front of the tragus. The labial artery may be controlled by compressing the lips between the finger and thumb. John H. Gibbon. Arteries, Surgery of the. — Wounds of arteries may be complete or incomplete, penetrating or nonpene- trating, perforating, punctured, incised, contused, or lacerated. It is generally said that a non-penetrating wound that does not injure the intima is not followed by hemorrhage and it has been shown experimentally many times that such wounds are not followed by aneurysm, as was formerly thought to be the case, 1ml by a scar stronger than the original wall of the artery. Punctured wounds may be caused by various for- eign bodies, the simplest form being a puncture by a 652 needle or pin. In these cases a small mural thrombus forms at the site of puncture composed of blood plates, fibrin, and leucocytes (white thrombus) comparable in a general way to a tack with the stem plugging the hole. Healing occurs without oblit- eration of the lumen. Punctured wounds may also be caused by many other foreign bodies such as scis- sors, fish bones, spicules of bone following fractures etc. Several cases have been reported of fatal hemorrhage from punctured wounds of the carotid and aorta by foreign bodies swallowed. Penetrating wounds may be complete or incomplete longitudinal, transverse, or oblique. When the wound is longitudinal it remains as a slit and little hemorrhage occurs, but when transverse, the edges retract, making the wound oval and the hemorrhage is greater. Oblique wounds gape somewhat from retraction, the amount depending on the obliquity of the cut. Gunshot wounds vary according to the type of missile used. The lead bullet used in former times, but now seen only in wounds in civil life, inflicts a contused or lacerated wound. The high velocity jack- eted bullet of modern warfare often makes a wound of the same type, but may make a clean-cut complete or incomplete wound. The missile may also wound both the artery and vein, traumatic aneurysm and arteriovenous aneurysm being common in the late wars. Shell wounds are rarely followed by immediate but are prone to delayed hemorrhage. The chief symptom of all these wounds is hemorrhage. Spontaneous hemostasis depends on the size and nature of the wound, the artery injured and its condition, the tension in the vessel, and on many other factors. When a vessel is divided the ends both contract and retract, narrowing the lumen, and the intima also tends to roll up, thus still further reducing the caliber. This contraction is due to the muscles of the Ar'terie" media and depends more or less on the (Schematic) aim mnt of stimulation. Following the injury there is an immediate hemorrhage and the blood coining in contact with the ad vent itia sheath into which the rest of the vessel has contracted formsaelotwhichex- tends around the wound for some distance 'j l h q e ua ^ ] and up into the lumen. This is soft and c , division ol is the red or temporary thrombus caused half the cir- by chemical action, and has nothing to do c u m ferenee with the white or true thrombus formed of the artety: later as the forerunner of permanent /» l '" ll, i' 1 ' t,! healing. The loss of blood also tends ^l 1 """] to stop the hemorrhage as it slows the <££2t0 current, and the bleeding may cease if the patient faints, only to recur when he regains consciousness and the pressure rises. Blood in exsanguinated subjects is said to clot more readily. The permanent or white thrombus is formed on the inside of the temporary or red clot and is composed of blood plates, leucocytes, and fibrin. It is always seen following any injury to the intima. The white thrombus is laid down slowly, and plugs the vessel to the nearest branch given off; in clean wounds it is firm and of a grayish color but in septic ones is soft, puriform, and loosely adherent to the vessel wall. It was in this class of wounds that secondary hemorrhage was so commonly seen in the days before aseptic surgery. Spontaneous hemostasis is retarded by increased tension following stimulation, unrest which dislodges the clot, or partial division only of the vessel, which prevents retraction and contraction. It is also retarded by anything that inhibits clotting. Contusion and Rupture. — These injuries may be Fig. 384a,— lougitudi- n a I; 6, ob- 1 i q u e ; c, tran SI 'i f its growth. If the vein is destroyed as well as the artery, gangrene is much more apt to occur and to be of the moist rather than the dry variety. Out if sixty-two cases of ruptured arteries collected by Berzog in 1S90, thirty-two or fifty-three per cent., i -veloped gangrene, while of Monod and Vanvert's fifty-eight cases of incomplete rupture, gangrene followed in thirty-five, or sixty per cent. These cases all occurred since the advent of aseptic surgery and were as follows: Subclavian four cases, no gang- rene; brachial seventeen cases, six gangrene; popli- teal seventeen cases, fifteen gangrene (although in another article the authors state that ligature of the popliteal should never be followed by gangrene). Jensen in an analysis of wounds of the popliteal artery found gangrene in fifty-four per cent. Fol- lowing ligature hi the femoral it is variously esti- mated as from five to forty per cent. Accordii the e statistic there ults are no better than before the advent of asepsis. They probably give a fal e im- pre ion, however, and it i-. to be supposed thai a large number of cases of rupture are treated and recover without being reported. Probably al o tl would be many fewer cases of gangrene if the le ion to the artery was recognized and treated promptly and in a systematic manner. In general it may be stated that simple rupture of the brachial artery promptly treated u never followed by gangrene, that of the axillary rarely. In the lower extremity gangrene is more common but practically never should OCCur after ligature of I he popliteal, although it should bo feared after ligature of the femoral or iliac. The symptoms caused by a wound in an artery may be divided into constitutional and local. The constitutional symptoms are primarily those of hemorrhage and shock and depend on the amount of blood lost and the type of the wound. The local symptoms are In— or diminution of the pulse in the vessel below the point of injury, pallor, a cold ex- tremity, and hemorrhage. The hemorrhage may be active and visible, when the skin is wounded, or it may be concealed, in which case a diffuse or circum- scribed arterial hematoma forms. The hemorrhage may also be delayed, if the wound is incomplete, or it may be recurring. Arterial hematoma occurs when there is a small wound in the vessel and may be either circumscribed or diffuse. In the diffuse variety the tissues are everywhere infiltrated with blood and no definite cavity is formed. The limb is swollen and cold, and the skin is tense and of a livid or bluish color. This causes great tension and pressure on the collaterals and predisposes to gangrene. In the more common or circumscribed form (false aneurysm) there is a sac formed out of the adjacent structures lined with fibrous tissue, clot, etc., and containing blood. This sac communicates with the lumen of the artery by a small opening and gives a distinct pulsating tumor of varying shape over which a distinct thrill may be felt and a bruit heard synchronous with the pulse. Lejars, Haga, and Russian surgeons have had occasion to treat a large number of these cases fol- lowing gunshot wounds made by the high velocity jacketed bullet in the late wars. The false aneu- rysm may form rapidly or slowly in the course of months, or may increase in size for a time and then cease, only to grow again later. If small there may be spontaneous cure, the cavity becoming filled with clot and obliterated. The treatment may be divided into constitutional and local measures. The constitutional treatment is the same as that for hemorrhage and shock and consists of rest in bed, morphine, artificial heat, stimulants, saline solution, transfusion, etc., as indicated. The object of the local treatment is first to control the hemorrhage and secondly to repair the damage done and prevent, if possible, gangrene. Imme- diately following the injury a tourniquet is generally applied as the quickest and easiest method of con- trolling the hemorrhage. The patient should then be removed to a suitable place and active local treat- ment instituted. The skin should be very carefully prepared and the vessel cut down upon and explored. The surrounding tissues and vessels are also to be carefully examined to determine the amount of dam- age done not only to the artery itself but to the satellite vein, the soft parts, and the collateral vessels. If the artery is lacerated and the vein intact the two ends may be ligated, the wound thoroughly cleansed of blood clot, and the skin sutured. The wound should be drained to relieve any pressure that might be 653 Arteries, Surgery of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES caused by the collection of serum. A thick dressing is then put on and the extremity kept warm, dry, elevated, and aseptic — in fact, everything should be done to promote the circulation. The above is the treatment indicated in the majority of the cases. If there is a small lateral wound in the artery it may be closed by suture or if it extends over two-thirds of the circumference the artery may be divided and end- to-end suture done. When the artery has been destroyed by the injury the bruised portion may be excised, the clots and thrombi washed out of the vessel with saline solution, and a piece of vein set in to remedy the defect. This is particularly indicated when the main vein is injured as well as the artery. The actual treatment of a given case depends on many factors and no definite rules can be laid down, the proper procedure being a matter of judgment. Treatment of Arterial Hematoma. — Diffuse hema- toma and also circumscribed hematoma when large and of rapid formation, should be treated on the lines already laid down. When circumscribed and of slow formation the majority of observers prefer to wait until a more or less definite connective-tissue sac is formed (false aneurysm) and the collateral circulation has had time to develop. There has been much discussion, however, as to the proper time to operate. In these late-forming cases the Matas operation is usually the procedure of choice. It is always well before operating to determine if possible the extent of the collateral circulation, which may be done by compressing the main artery and noting if this obliterates the pulse and noting also the ap- pearance of the limb beyond the aneurysm. Inter- mittent pressure applied in this manner also tends to develop the collateral circulation. During the opera- tion some form of temporary hemostasis should be employed and the vessel treated according to the condition found. In many cases the restorative Matas operation can be performed. In others double mediate ligation is necessary, while in some arterial suture may be employed. Monod and Vanvert (1011) have collected 215 operations done for this condition on 20.5 patients since 1880. Suture was performed in thirty-two of these with twenty-nine successes, one death and one failure, while in one the result was not noted. Healing of Arteries. — This subject has been ex- tensively studied by Zahn, Pitres, Warren, d'Eberth, Schimmelbusch, and others and is essentially the same when following a wound as when following ex- perimental ligature. When a large artery is tied in its continuity, the intima and a variable portion of the media are usually ruptured, and the adventitia is gathered into a dense tendinous sheath around the constricted ends. The first noticeable change is the formation of the thrombi. The proximal thrombus is much larger than the distal thrombus and owing to the more rapid coagu- lation of the blood the vessel has an ampulla-like distention. The vessel on the distal side of the ligature is contracted and the thrombus is much smaller. The ligature soon becomes embedded in a cell growth which appears to proceed from the peri- adventitial tissue, and varies according to the amount of injury done by the ligature to the vessel walls, or to the irritation which it produces. If the coats of the vessel have been unnecessarily bruised and a certain amount of extravasation has taken place in consequence, or if the ligature itself, for some cause, has created irritation, the surrounding inflammatory tissue will form a well-marked callus. If an excessive irritation has been produced, the growth of this protective tissue may be retarded, or it may be destroyed and the danger of hemorrhage correspond- ingly increased. Following the development of this external growth, we find that it extends some distance up and down the sides of the vessel in the periadventitial tissue, the round cells of which it is composed invading only the superficial layers of the adventitia; the breadth of the growth is, of course, greatest at the point of ligature; in length it reaches usually to a point on a level with the ends of the two a _ 6 c WM Fig. 385. — Ligatured Vessel, a, Proximal thrombus in ampulla, like dilatation of the vessel; 6, media; c, adventitia; I, site of ligature. (Drawn from author's specimen.) thrombi; when fully developed it is consequently spindle-shaped (Fig. 3S5). At the point of ligature, where the fibers of the outer wall are densely packed (Fig. 385, I), the cell growth does not penetrate dur- ing the first few days; but just above and below the ligature they may be found already invading the media as early as the second day; occasionally the apex of a pyramidal-shaped mass of such cells will have reached the thrombus. These cells appear to exert a solvent action on the bunch of fibers projecting from the ring of the ligature, which thus becomes gradually liber- ated from all connection with the vessel, the two ends of which now retract and leave the knot embedded in the center of the callus. The fibers of the ligature itself soon become infiltrated with cells, and by the tenth day they may have already dis- appeared, or, if its resisting powers are greater, may re- main encysted for some time. The period which the ligature requires for this separation varies greatly ac- cording to the size of the vessel and character of the ligature, and is longer in man than in animals. If the artery has been properly dissected out, this external growth will be observed forming a callus-like ring, in which the two ends of the vessel are embedded, in size about twice the thickness of the vessel, and it can still be seen well developed at the end of two months (Fig. 3S6). In the specimen from which the accompanying drawing was taken the ligature had caused suppuration about it, and had formed a fistulous track at the fundus of which some fibers were found still remaining. By the end of three Fig. 3S6.— Carotid Artery of Horse Two Months Alter Ligature. I, Sinus at site of ligature; the ends of the artery have separated, but are enclosed in a firm callus. (Drawn from author's .speci- men.) G54 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries, Surgery of callus had disappeared, and united the peripheral to the onths the external ,ly a slender cord roxiroal end. \lrcady by the fourth day changes are noticed it hin the vessel. Observing the proximal thrombus , find an increase in the number of while corpuscles, irticularly near the point of ligature, not in an ulated mass, but mingled with red corpuscles. asses of coagulated fibrin with young cells i while irpuscles of clot, wandering cells from arterial ,:its and rarely also periarterial tissues) are at Inched . I lie frayed ends of the media which have been i by the ligature and are more or less inverted, lie endothelial cells, when not firmly compressed y the thrombus, as in the distal end, are in a stale ity, undergoing proliferation to a moderate stent. Occasionally, loop-like masses of cells may ■ seen projecting into the clot, or a delicate anas- mosing network of stellate or spindle-shaped cells; nt the total amount of this cell growth is small as impared with the size of the thrombus. In the .an time, in the second week, masses of granulation lis ate seen infiltrating that part of the wall which separating or has already separated from the ature. Even at this period, with the external rowth carefully dissected away, as is the custom in iliseum specimens, the vessel appears to have united \ first intention, that is, by a direct union of the icdia and intima side to side. But the infiltration rid softening continue until the walls are separated ad expand, like the petals of a rose, yielding before he advancing growth of granulation tissue. The ceper portions of the clot are now infiltrated with wo growths; the more superficial (that is, the por- lon nearest the open lumen of the vessel) is com- osed of tissue grown from the intima and media and .andcring cells, and the deeper is composed of vas- ular granulation tissue which has pushed its way in roin without. Viewed at the thisd week, the ends f the vessel will be found expanded and the space etween them filled with well-formed granulations, Mrh as are seen on the surface of a healthy wound. \ portion of the thrombus, sometimes a large portion, iss not been infiltrated, but is attached firmly to the op. A longitudinal section of such a specimen gives a triking illustration of what is understood as "healing ly scabbing." As the clot shrinks the spaces left be- ween the granulations, which have now rolled over me another in cloud-like masses, become continuous \ith the open lumen of the vessel, and the so-called canalization" of the thrombus is thus effected. An njection mass can be forced from the vessel for some listance into these spaces, but as yet they do not •ommunieate with the vessels of the granulation issue. This communication usually does not occur mtil the second month, that is, until the provisional growth has reached its period of highest development. The vessel walls have in the mean time been under- ming certain changes. A proliferation of the cells if the intima, as has been noticed by so many ob- servers, unquestionably takes place; but the amount li-velopcd is not sufficient to supply more than a t cry small part of the provisional tissue. The cells, however, have begun to grow before the other tissue lias made its way into the vessel, and at this period serve the purpose of attaching the thrombus to the walls of the vessel, but even in this work they are aided by other cells from the media. They also furnish a new endothelial covering to the permanent cicatrix, and a lining to the new vascular spaces that have been formed. When the elastic lamina has been ruptured (and this is frequently seen on the -ides of the vessel near the ligature, and also here and there higher up as far as the thrombus extends), we find an intimate connection at such points of the media with new growing tissue within the vessel. In the second week, cells may be seen springing from the media and growing into either the clot or a clump Fio. 387. — Carotid Artery of Dog Four Months After Ligature, showing shape of cicatrix as modified by the presence of a branch. (Drawn from author's specimen.) of cells attached to the inner wall. The cells are round and spindle-shaped, frequently in bundle . Evidences of cell activity in the media are abundant, and in some specimens in animals a proliferation of the muscular cells through the whole thickness of the media is ob- served, giving a con iderable in- ffillllA m»W elrne l.i Ihr width Uk of this layer. The clastic lamina is frayed out at its divided end, and glistening elastic lilier, are seen ex- tending downward into the external growth as the two ends of the vessel gradually retract from each other. At the end of three months the provi- sional t issue has been absorbed, and we find the walls united by a perma- nent cicatrix which joins the sides of the vessel, still somewhat separ- ated from each other. It consists, in medium-sized arteries, of a cres- cent-shaped mass of tissue, the concave side of which faces the lumen, while the horns run up on either side of the vessel. One horn may be long and the other short, the crescent being placed somewhat excentrically. The longer horn may be sometimes thickened (see Schultz and Thoma), as in Fig. 3S7, if a branch lies opposite to it. In the largest vessels the cicatricial tissue occupies a con- siderable portion of the caliber of the vessel. On the surface of the cicatrix is seen a thin layer of endothelium; beneath this, in medium-sized vessels, there can be seen a layer of delicate, tapering, spindle cells with staff-shaped nuclei, forming a continuous layer from one horn to the other. They run parallel to one another and to the arc of the circle made by the crescent, and resemble in all respects muscular cells; in short, a genuine muscular layer is found here (Fig. 3S8). Be- neath this layer is a mass of cicatricial connective tissue which plugs the space lying directly between the ends of the retracted walls (Fig. 389). The cicatrix is pierced by a vessel of considerable size which rapidly tapers to a point and anastomoses with a capillary network, ramify- ing both in the cicatrix itself and in the ligamentous band outside. This central vessel, which in larger cicatrices becomes tortuous and gives to the cicatricial tissue a "cavernous" appearance, may be regarded as the unobliterated residuum of the lumen. We find in this anatomical peculiarity of the cica- Fig. 388.— New Muscular Cells in the Cicatrix; from the femoral artery of a dog three months after ligature. (Drawn from author's speci- men.) G55 Arteries, Surgery of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES fcrix an explanation of its immunity from aneurysmal dilatation. The protective influence of the thrombus enables the process of cicatrization to complete itself before the cicatrix is called upon to withstand blood pressure, and it is then armed with a muscular coat (as is the normal vessel wall), which acts not unlike a levator ani muscle in sustaining and modulating the force of the blood column. The ligament which unites the two ends of the vessel represents, in part, the residue of the external callus; it has become much elongated by the retraction of the two ends. During the healing process, a small pi lit ion of the vessel walls has become disintegrated by the new growth, and a portion has atrophied and ML WW I t.V FlO. 389. — External iliac Artery of Man One Hundred and Thirty Days After Ligature: formation of permanent cicatrix. (Drawn from author's specimen.) has been absorbed, the remaining walls have shrunk greatly by retraction, and their caliber has been filled to a greater or less extent by a cicatricial tissue; so that the vessel has become practically obliterated up to the first branches of the collateral circulation. The thrombus is a mere passive structure, and takes no part in the growth, but is protective and affords an excellent medium for the germination of the new tissue. Its upper portion is not penetrated by the new growth, but rests upon it and forms a sort of protecting scab. It is deposited gradually, and has a stratified appearance. Its size appears to be dependent upon the amount of injury done to the vessel and the resulting inflammation. If the intima or the elastic lamina has been ruptured in handling the vessel, as can frequently be demonstrated by the microscope, some distance from the point of ligature, clots will form at these points, and the thrombus will thus become elongated. Occasionally, the apex is formed of white corpuscles only, and may be free or lightly attached to the wall by a cell growth from the intima. Thrombosis and Embolism. — Arteriotomy for the removal of a clot plugging a vessel, either a thrombus or an embolus, and the restoration of the circulation has been practiced a few times, but has not been generally successful. There are three types of embolism that have been subjected to operative treatment or for which opera- tion has been suggested, viz., embolism of the extremi- ties, pulmonary embolism, and mesenteric embolism. Emboli of the extremities, unless of traumatic origin, are practically always seen only in disease of the left side of the heart and are more common in the lower than the upper extremity. Barie in an analysis of fifty-four cases found the emboli situated as follows: tioial artery fifteen, femoral twelve, iliac nine, popli- teal seven, dorsalis pedis one, arteries of the fore- arm four, subclavian three, axillary two. They may lodge in the aorta even, in which case there is sudden acute pain referred to the abdomen and paralysis of the lower extremities in addition to the usual symptoms of cold and loss of pulse below the obstruction. Mniiod and Vanvert (1909) collected ten cases of arteriotomy for the removal of a clot and Delbet and Mocquot (1911) mention fifteen, none of which were perfectly successful. The chief difficulty is in making the diagnosis early enough to render the operation of value, as secondary degenerative changes take place very rapidly in the intima at the point of lodgment of the clot so that even if the embolus is successfully removed a second clot forms at the same site on the damaged intima in a short time. In one of Stewart's cases the clot formed twice after repeated arteriotomy, and excision of the damaged portion of the artery with end-to-end anastomosis was later performed. This also became plugged and amputation was resorted to some time later. Tixier has more recently performed an excision of a portion of the brachial artery for an embolus with end-to-end anastomosis successfully. Another difficulty in these cases is in exactly locating the point in the vessel at which the embolus is impacted. At times this is comparatively easy, but the symptoms are as a rule referred to a portion of the limb considerably below the seat of injury. There are certain points, however, at which the embolus is apt to lodge such as the bifurcation of the aorta, at the division of the popliteal, or in the femoral artery where the profunda is given off. These cases of arterial emboli also usually occur in the a^ed and this fact makes operative interference difficult as the walls of the vessels are stiff and atheromatous. Thrombosis or embolism of the main artery of a limb is usually followed by gangrene, but this is not necessarily always the case. The symptoms of emboli of the extremities are usually acute pain, pallor, and loss of pulse and cold- ness below the obstruction. Later there may be both motor and sensory paralysis in a varying degree, followed, if there is no collateral circulation, In gangrene. In a few cases reported the symptoms nave been of slow onset and have not been accom- panied by great pain.. Operative treatment consists in arteriotomy with removal of the clot, followed by rest, heat to the limb, and measures to promote collateral circulation and prevent the reformation of the clot. If gangrene supervenes amputation should be performed. Hand- ley has tried, unsuccessfully, to dislodge a clot situated at the bifurcation of the aorta by passing a catheter up the femoral artery, and it has been suggested that this be done in emboli of the femoral artery in order that amputation might be done at a lower level than would otherwise be necessary. The operation of arteriovenous anastomosis, or biterminal graft, may also be performed when the diagnosis is made early enough and the vessel walls are in good condition. Pulmonary Embolism. — In 1907 Trendelenburg devised an operation for the removal of an embolus in the pulmonary artery which has been performed four times, twice by him and twice by other surgeons. One of the patients lived for five days. Mesenteric Embolism. — Emboli "of the mesenteric vessels usually lodge in the superior mesenteric artery which is to all intents a terminal artery. No 656 REFERENCE IIANDHt >(>K OF Till', MEDICAL SCIENCES Artcrtcs, Surgery of ise has yet been treated by arteriotomy and the imoval of the clot, although the operation has been ted by several obsen ers. i koi. of Hemorrhage. The methods of use control of hemorrhage are heat, cold, elevation, yptics, compression either direct or indirect, acupres- forcipressure, torsion, ligature, and suture. in mimic form, as cold compresses, ice, cold etc., lias I ii used in the control of he ■- from ili" earliest times and has a distinct \ alue ain slight forms, but is not adequate to control hemorrhage from a large artery. ii the form of the actual cautery was the chief leans of controlling bleeding during the Middle \v i.l in fact was used by many surgeons during the ighteenth century. Although discarded at the pre it day for the ligature, it is used in a modified form certain cases, as in the clamp and cautery opera! ton i hemorrhoids, in certain operations on the bladder id nose, and as the electrothermic angiotribe. Vhen the tissues are charred an eschar forms, plug- ing tlic vessel and later separating as a slough. \tion of a part is of value in controlling slight emorrhage, especially when it is venous in character. Styptics are rarely employed at the present day. it are of service in stopping ooze from small Most of them act by causing the blood .1 clot at once, and they make an extremely foul ,ound. Adrenalin is by far the best and most useful and acts by causing a contraction of the essels. It is used in strengths of from 1 to 10,000 n 1 to 1.000. Compression may be either direct or indirect and is he most valuable means at hand for the immediate ontrol of hemorrhage from a large artery. Indirect 'impression is the method usually employed as a rst aid measure; this may be either mechanical or ligital. The best example of mechanical compression 3 the well-known tourniquet or Esmarch bandage, tigital compression of the main artery of a limb is less pi to injure the structures, but is very difficult to uaintain for any length of time. Nearly all the large essels can be compressed against some bony promi- "iice with comparative ease and the circulation con- rolled for some time if relays of assistants are at land. While indirect compression is invaluable as a uethod of expediency, it cannot be employed to con- rol the hemorrhage permanently. In direct or im- mediate compression the pressure is made directly on he bleeding point. It may be either digital or by nuking a wound with gauze sponges, and is of especial alue in stopping a general ooze from a large raw Torsion was not unknown to the ancients, and was employed by certain surgeons in the Middle Ages; but a more modern times, practitioners were not familiar •vith it until it was brought to the notice of French trgeons by certain statements of a visitor from iennany. Both Velpeau and Amussat apparently laimed the credit of introducing it, the former in onsequence of his experience, when a student with a veterinary surgeon, in the twisting of the pedicle in paying and castration, and both as the result of their it ions on the immunity from hemorrhage in edarteries. The method employed by Velpeau is thus described: "After having seized the vessel by its extremity. I separate it from the surrounding and grasp it. at its deepest point in the wound, mother forceps, to hold it firmly while it is I lined on its axis, three to eight times", by the first forceps." He appears to have employed the method in several amputations. Its supposed advan- - the avoidance of a foreign body in the wound. ' ■ iignized the fact that animal ligatures would be equally good for this purpose, and also the disadvan- tage of torsion in diseased vessels, and that small were not easily isolated. The effect of torsion, Vol. I.— 42 according to Bryant, is a twisting of the ela tii B of the adventitia bi yond the end of the vessel, and a retraction and incurvation of the middle and inner coats; the twist in the outer coal is permanent and cannot lie unfolded by any legitimate force; the middle and inner coats are una' ted in the direction oppo ed to tin' lil I stream, approximated and over- lapped. The safety from hemorrhage rest upon the twist of the external, the retraction of the internal coats, and the coagulation down to the firsl branch; while, in acupre ure, the permanent safety depends upon the lasl alone, temporary protection being afforded by the needle. Kocher found numerous and irregular In of the inner coats over a considerable distance of the wall, and independent of one aunt her, while in liga the ruptures were circular and only close to the point of liga! inn. I n unlimited torsion there is considerable nan-owing of the lumen. ( Iwing to these peculiarities, it has the advantage of favoring a rapid coagulation. Acupn ture. — The introduction of this method of hemostasis, which at present is chiefly of historic interest, is to be accredited to Sir .lames Simp on unless an obscure passage in John de Vigo's writings be interpreted otherwise than as a description of the ordinary ligature). He saw in the ligature a foreign body in the wound which cut through the two coats at the time of its application, and ate through the outer coat. It was for this reason principally that amputation stumps healed with so much greater difficulty than wounds in the operation for vesico- vaginal fistula, although the latter were constantly bathed in leucorrheal discharges and urine. The application of the ligature isolated a portion of the end of the vessel, which remained in the wound as a piece of dead flesh until it came away with the ligature. The needle, on the other hand, did no injury to the vessel and caused no irritation, its use being based upon "the great pathological law of the tolerance of living tissues for the contact of metallic bodies em- bedded in their substance." Bryant showed, how- ever, that the ligatured portion did not slough, but became adherent and vascularized. Although English surgeons supposed that no injury was done to the vessel by the needle, Kocher and other German writers demonstrated longitudinal slits in the intima, but not so extensive as those occurring in torsion. The vessel is thrown into longitudinal folds, which become sufficiently firmly glued together to retain this shape long enough, after the removal of the needle, for the thrombus to form and become firmly attached to the walls. A specimen examined by Kocher at the end of twenty-two hours showed no thrombus, the walls being compressed and somewhat thickened, but a fine probe could be introduced between them. At thirty-six hours a well-formed, egg-shaped thrombus is represented by Shakespeare. A drawing by Kocher shows a specimen fourteen days old, in which the walls have already separated from each other, and the thrombus is short and wide, having a concave surface on the side toward the lumen, and a convex surface at the other end. The relation which the thrombus bears to the vessel is that of a cork to a bottle, beyond the neck of which it does not project. It is probable that the apex had been detached. In acupressure in the continuity, the proximal and peripheral ends of the thrombus are continuous, as are also the walls of the vessel, which at first are thickened by a connective-tissue growth; the sub- sequent changes differ in no way from those already described. Ogston tested mechanically the comparative strength of arteries secured by ligature, acupressure, and torsion, by subjecting them to the pressure of a column of mercury. It was found that a column one hundred and fourteen inches in height was insufficient to rupture the ligatured artery. Twisted vessels 657 Arteries, Surgery of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES unfolded at an average height of thirteen inches (or a pressure of 6.5 pounds to the square inch). In acupressure, the column of mercury showed an average height of 23.5 inches. It would, therefore, seem a more reliable method, he says, than torsion, and less reliable than ligature. Forcipressure. — This is a very convenient method of stopping bleeding from both arteries and veins and is employed universally, but chiefly as a temporary expedient preliminary to ligature. It was used by Desault in 1786 only to fall into disuse and was reintroduced about 1865. The clamp, or hemostatic forceps, now in use is a modification of that invented by Pean in 1808. When a vessel is clamped the two inner coats are ruptured and the ends curl back plugging the lumen and favoring clotting while the adventitia is transformed by the pressure into a homo- geneous band. Although in the larger vessels it is customary to follow this with ligature, in the smaller it is unnecessary. Certain operators using the angiotribe, a special broad-bladed crushing forceps, do not ligate even the larger arteries. In certain other cases such as in vaginal hysterectomy, where ligature is difficult forceps may be left in place for several hours and then removed with but little danger of hemorrhage. The length of time necessary to leave a clamp in place in order to insure permanent hemostasis has been estimated by Bothezat at sixteen hours for a vessel the size of the radial artery, and eighteen for one as large as the femoral, but cases of secondary hemorrhage have been reported after vaginal hysterectomy when the clamps have been left in place for twenty-four hours. Hopfner, Payr, and Crile clamps exert forms of forcipressure, but they are used only for temporary hemostasis and should be carefully applied in order not to injure the intima. Their use is sometimes followed by thrombus formation. Ligature. — Although the introduction of the liga- ture is commonly ascribed to Par6, there is suffi- cient evidence to show that it was employed by surgeons in the earliest historic times. No mention is made of the ligature by Hippocrates, but the ancients used not only styptics and the actual cautery, but also ligature and torsion. It is highly probable that the Alexandrians were familiar with the use of the ligature three centuries before the Christian era, for Celsus (born 30 B.C.) speaks of it as a well-known fact and recommends its use. Archigenes and Galen both mention tying vessels for the purpose of stopping hemorrhage; the name of Antyllus also bears testi- mony to the skill of Roman surgeons, and in the Museum at Naples there may be seen a forceps, with sliding attachment, evidently intended to use with the ligature. We find the ligature of arteries mentioned again in the seventh century by Paulus of yEgina, whose teachings were still preserved by the Italians in the sixteenth century. It is uncertain, however, whether ligatures were em- ployed on large vessels before Pare's time. To this great surgeon is due the credit not only of fully appre- ciating the value of this mode of hemostasis, but of making it a universally applicable method. At this period, the middle of the sixteenth century, the imper- fect knowledge of the anatomy and physiology of the circulation prevented a due appreciation of the ad- vantages of the ligature, and even Guillemeau, who was the champion of his friend and teacher, confined the use of the ligature to primary amputations. Although Wiseman in England, Fabricius Hildanus in Germany, Fallopius, and others favored the ligature, they were but isolated examples, and at the opening of the eighteenth century the actual cautery was still the customary method of arresting hemorrhage at the Hotel-Dieu. The contrast between the two methods at that time was not indeed as great as it would seem to-day. A glance at Parti's plates shows the forceps as an instru- ment of rude pattern and clumsy make; no attempt was made to isolate the vessel; veins, nerves, and arteries being included in one knot. No wonder that surgeons had a " horrid apprehension of compressing the nerves," and that Petit, with whom modern investigation on the healing of arteries may be said to have begun, actually proposed compression as a substitute for the ligature. It was he who first called attention to the agency of the thrombus in checking bleeding, the blood around the end of the vessel being termed the couvercle, and that found within the lumen the bouchon. The retraction and contraction of the vessel w-ere soon recognized by Morand, who also called attention to the rupture of the inner walls by the ligature. To Jones has been pretty generally accorded the credit of producing the classical work upon this subject. By a large and varied series of experiments on animals he was able to give a complete account of the macroscopical appearances showing injuries to arteries, which account, in the main, holds good to- day. He found that when a large artery was divided it retracted into its sheath, and contracted slightly at its extremity (a coagulum forming within the sheath and external to the vessel, and appearing like a continuation of the artery); and that later a slender and conical coagulum formed within the vessel, being only partially adherent to its walls. • It was chiefly due to Jones' investigations that the modern single thread was adopted. Cutting short both ends of the knot was adopted in 1798 by an Ameriican naval surgeon. The disadvantage of a silk or hempen ligature was supposed to be due to its non-absorption. The introduction of the absorbable ligature is generally ascribed to Physick whose liga- tures were made of chamois leather rubbed on a slab to render them hard and round. Sir Astley Cooper tried them and they were used in this country by Jamieson of Washington. Absorbable ligatures did not come into general use till Lister published his method of preparation with carbolic and chromic acid. At the present day absorbable ligatures, represented by plain and chromicized catgut, are more commonly used than the non-absorbable. The chromic gut was introduced as plain catgut is absorbed at times very rapidly, while the chromic gut resists the action of the tissues for a varying period, depending on the length of time it is treated with the acid, and in fact occasionally it is never absorbed. Of the other forms of animal ligature kangaroo and ox tendon are the two in most common use. Of the non-absorbable at the present day, Pagenstecher and linen are used as freely as silk. There was formerly a great deal of discussion as to the tightness with which the first knot of a liga- ture should be tied and Ballance and Edmunds tried to introduce a soft ligature with the first knot tied so as to approximate the intima without rupturing it. It is accepted now, however, that the first knot should be tied with enough force to rupture the intima and part of the media. Metallic ligatures are rarely used to-day except to diminish the caliber of a large artery leading into an aneurysm, dishing has recently suggested the use of small pieces of silver wire as ligatures applied with a special clamp for the control of bleeding from ve- in an inaccessible position. These are comparable to the "skin clips" and have proved of value in cerebral surgery. Temporary ligatures are occasion-' ally used to control hemorrhage and for this purpose tape or floss silk is the best material. Suture. — The first suture of an artery was done by Hallowell at the suggestion of Lambert in 1759. He successfully closed a wound in a brachial artery made during a venesection, by pinning the edges of the wound together with a needle held in place by B figure-of-eight suture. Asman in 1773 did a series of experiments on dogs using this technique, and found 658 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries* Surgery of ii although hemorrhage was perfectly controlled a rombus always resulted and these views have held iil comparatively recent times. The first success- blood-vessel anastomosis was performed in 1879 a Russian surgeon, who made a lateral istomosis between the vena cava and the portal in — the .so-called Eck fistula. reporting in a classical article the first successful < i i of circular suture in man. Be ha In© described a modification of this method using a removable cylinder in two pieces as a support which brings intima more nearly in conjunction with intima. The original method consisted in passing a suture through the wall of the distal end of the vessel which is brought out W' .1 B Fig. 390. — Murphy's Invagination Mcih.nl. A, Two the threads designed to invaginate the proximal into e distal end of the artery have been passed; B t the agination completed, showing also the superficial laptation suture. (Delbet ana Moequot.) A B C Fig. 392. — Payr's Method. .4, The tube is placed in the proximal end of the divided artery; B t the proximal end of the divided artery is turned back over the tube and tied to it; C, the invagination is complete, the distal end of the artery being passed over the proximal end and tied there. (Delbet and Moequot.) Gliick in 1883 showed that the repair of lateral "iiids of arteries was possible, although most of his vperiinents were failures. In 1SS9 Jassinowski tade a series of experiments and showed that it was ossible to get healing in lateral wounds of arteries ithout thrombosis. He used fine silk as a suture taterial and was able to close wounds that did not through the lumen and caught the proximal end through the outer coats only. Three such sutures are placed about three-fourths of an inch from the end of the artery. By traction on these the proximal end is then invaginated into the distal, and the anastomo- sis is completed with interrupted or a continuous stitch to make a tight joint. (Fig. 390.) Nitze in I SB 1 [ fl -«t A LyX m V* - If 5?. * 3 .' «• ' fa 1 ■i \ i. : .,' io. 391. — The Jaboulay-Brian Method of Vertical U-shaped Sutures. (Delbet and Moequot.) Fig. 393. — Showing Repair of an Artery after Suture. and Obstetrics.) (iSwgery, G'i//' : •xceed two-thirds of the circumference of the artery, twenty-four of his twenty-six experiments being successful. His sutures did not penetrate the intima. In the next few years many articles were written, but Few successful cases were reported. In 1894 Abbe sug- gested doing end-to-end suture over a glass bobbin. In 1S97 Murphy introduced his invagination method the same year performed a circular suture by turning back one end of the vessel over an ivory ring making a cuff over which the other end of the artery was drawn. Soon after this Jaboulay and Brian suggested, in circular suture, splitting the vessel up for a short distance and suturing the ends together with U- shaped sutures bringing intima to intimr, — the broad 659 Arteries, Sui'scry of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES marginal confrontation method. (Fig. 391.) Dorfler in 1.S99 described a method of arterial suture in which he used small round needles and silk, the suture being continuous and penetrating all the coats. His method, modified and perfected, is the one commonly em- ployed to-day. In 1900, Payr published a method which was popu- lar for a time and which is satisfactory. He used magnesium cylinders similar to Nitze's ring, but absorbable, on which were one or two circular grooves. One end of the severed artery was passed through the cylinder, turned back as a cuff and tied into the upper groove. The other end of the vessel was then drawn over it and tied into the lower groove. (Fig. 392.) Crile's transfusion cannula? are very similar to (his ring. Later Payr advocated another method, using two cylinders with a broad flange. In 190., Berard and Carrel published a method similar to the Dorfler method only the stitches did not penetrate the intima. Later as the result of experiments with Morel and in 1905 with Guthrie, Carrel developed the technique which is used practically without modification at the present day. Many other methods of arterial suture have been published. Salomoni independently published a suture similar to that of Jaboulay. De Gatano suggested using an intravasal apparatus, while Lepi- nasse used broad metal flanges. Dorrance has a special stitch for use in lateral wounds, and Brewer in these cases has wrapped the vessel with adhesive plaster. Repair after Suture. — Healing after suture occurs with a varying amount of scar depending on the degree of trauma and the accuracy with which the parts are brought into apposition. In a well-performed opera- tion the resulting scar is very slight. The intima unites completely forming a smooth lining to the ves- sel. There is some difference of opinion as to the fate of the elastic tissue and while in some cases it regen- erates, in others the defect is filled in with scar tissue. The media often completely regenerates and shows no visible scar. (Fig. 393.) The success of arterial suture depends on absolute asepsis and good technique and now experimentally in the hands of men accustomed to the work is rarely unsuccessful. The history of the repair of arteries is thus comparable to that of intestinal repair, where complicated mechanical devices have been replaced by the simple needle and thread with good technique. In 1900, Dorfler stated that there were reports of but nine successful cases of arterial suture in literature, while in 1909 Monod and Vanverts collected sixty- five and Stich in 1910 stated there were over one hundred. Operations for circular suture of arteries may be divided roughly into three classes: (1) The invagina- tion method of Murphy; (2) Suture with the aid of some mechanical apparatus (Payr); (3) Direct suture (Jaboulay, Carrel). In the invagination method the blood comes in direct contact with quite a large raw surface and is very liable to clot. In many of the me; hods the lumen is narrowed by the use of a cuff or ring and a large amount of slack vessel is necessary, or a mechanical device difficult to handle must be used. Suture for incised longitudinal or transverse wounds, lateral suture, is almost always successful at the pres- ent day in the hands of men trained in blood-vessel surgery in the laboratory. Of the sixty-six cases collected by Monod and Vanverts there was only one failure, but it was impossible in many of these to prove the permeability of the vessel. The absence of ■ ragrene after the suture of a wound in the main artery of a limb ami the presence of a pulse do not in any way prove the patency of the artery, as gangrene does not necessarily follow ligature, the collaterals taking care of the circulation very rapidly. In certain cases, however, small emboli may break off from the mural thrombus at the site of the suture and give rise to small areas of gangrene. The scar follow- ing suture is as strong as the vessel wall and never gives rise to an aneurysm. Comparative Value of Suture aud Ligature. — The value of circular suture in human surgery is not yet on as firm a basis although several successful rases have been reported. Braun has reported a ci of circular suture of the aorta which was torn in removing a large adherent pelvic tumor from a young girl; convalescence was uneventful. It has also been done several times in reversal of the circulation. Besides end-to-end and lateral suture, end-to-side and side-to-side may also be clone. Much has been written on the respective value of suture or ligature in wounds of special arteries, and the question is not yet settled. Suture should be preferred in all longitudinal wounds of the large arteries of the limbs where it can be done with some hope of success. It should also be done when liga- ture of the artery in question is apt to be followed by gangrene, although the frequency with which gan- grene occurs as the result of ligature of a given artery varies greatly in the statistics compiled by the differ- ent observers. If the ends of the vessel cannot be brought together without undue tension bj' flexicn of the limb, loss of substance can be repaired by grafting in a piece of vein to take the place of the artery destroyed or resected — the biterminal graft of Carrel. When the blood is allowed to pass through the vessel again the grafted portion of vein becomes at first greatly distended but in course of time it contracts, the walls become thickened, and it takes on the general characteristics of an artery. Grafts for loss of substance may be either autoplastic, where a vein of the patient is utilized, or heteroplastic, where a vessel from another person or animal is used. Ex- perimentally this has been done with success, portions of dog's vessels having been grafted in the fresh state and also after having been kept on ice or preserved in formalin for weeks. Suture of arterial wounds is a recognized surgical procedure and to be done when necessary but never when the collateral circulation is sufficient to nourish the part, in crushed and septic wounds, or when tension is necessary to bring the ends of the vessel in apposi- tion. It should be done only on large arteries and it is difficult and unnecessary to perform suture on anything smaller than the popliteal. Ligature should be preferred to suture unless the surgeon has the facilities at hand to perform a satisfactory opera- tion and has had laboratory training in the repair of arteries. Besides its value in the repair of wounds, suture may be done for the reversal of the circulation, in the treatment of arteriovenous aneurysm, and in a modi- fied form in the repair of common aneurysm (Matas operation). Technique of Arteriorrhaphu. — In arterial suture special light instruments are necessary such as are used in the physiological laboratory in experiments on small animals. The special kit consists of three or four pairs of fine straight or curved dissecting forceps without teeth, or jewelers forceps with the cuds rounded and smoothed; two or three pairs of fine very sharp scissors, one curved on the straight; six M eight mosquito forceps, and a sharp fine-pointed knife. Temporary hemostasis is absolutely necessary and may be obtained by several methods. When the artery to be repaired is in the extremity, a tourniquet maybe applied to the limb, but this is rarely possil le ami it is also usually better to control the hemorrhage from the artery by some form of hemostasis in the wound itself. Many forms of clamps have been in- vented but probably the best form is the old-fashioned serrefine. These should be small and light with a spring strong enough to control the hemorrhage but 6G0 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arteries, surgery of ,i to injure I In- intima. The corrugated blades are i protected by being wound with thread or covered ith thin rubber. Hopfner, Payr, or Crile clamps may ■ used instead, the pressure in these being regulated v a thumb screw. In large arteries it is probably ii,,- to place one of these on the artery above the e to prevent accident in case the latter should ip, Another method of temporary hemostasis is by grounding the artery with a piece of tape which is rawn taut, occluding the vessel, the ends being then Ivy a pair of hemostatic forceps (Fig. 394). irculation may also be slopped by kinking the vessel ith a piece of tape passed under it. by digital pres- u. 394. — Showing Two Efficient Methods of Temporarily Occlud- ing Vessels for Suturing. (Guthrie.) ire made by an assistant, or by temporary liga- tre. Floss silk or tape is the best for temporary liga- on but none of these methods is as universally pplicable or satisfactory as the small serrefine or lamp. The needles commonly employed are Kirby No. 2, 14, or 16, depending on the size of the artery. luthrie recommends No. 12 for arteries four milli- leters in diameter or more, No. 14 if the vessel is mailer. The needles should be highly polished, ■ee from rust, and have a small eye. Silk is probably he best suture material although human hair is ivored by some surgeons. The silk used is the ntwisted floss silk. Guthrie uses "bead silk" com- osed, as are all silk threads, of three strands each of Inch is made up of two others. The silk is divided ito its three strands and these are used for sutures or, finer ones are wanted, each of these may be again ivided. Horsley uses No. 1 black Chinese silk un- wisteil into its three component strands. Many f the surgical supply houses now have special silk ir this work or it may be obtained already threaded ml sterilized in oil in tubes, similar to the catgut gatures. The silk should be of good quality, mooth, and with a tensile strength of from three unces to five ounces. Sutures are prepared before- land, tied in the needle, with one end cut off short, ml should be about eighteen inches long. Two are nough for most operations although it is well to have i'ic at hand. After being threaded the needles are hrust through a card and the silk wrapped around he latter. They are then put in a small bottle or iox filled with liquid vaseline and sterilized by •oiling cither with the instruments at the time of iperation or beforehand. Instruments are sterilized iy boiling as for any operation. End-to-end Anastomosis. — The incision is made in he usual manner and the vessel exposed. The lamps for temporary hemostasis are then applied to the artery, I he tourniquet . il one i i , i removed, and all small bleeding points arc tied. It IS well to put a strip of lint-free waterprool material undei the artery at the point where the anastomosis is to be made, of a dark color if white silk is being used and white if the silk is black. Tin- vessel is then washed out with saline soluti in to remove any clot and tl e edges are trimmed smooth and even. A knife bruises the tissues less but scissors make a mole . i ii cut and should lie preferred if t hey are --harp. If the artery has contracted into its sheath the ad ventitia is pulled down and cut off. Three slay or guide sul urcs arc then applied at points equidistant about the artery, one being placed directly posterior. They pass from without inward about one millimeter from (he edge t h rough all the coat oi the distal end of the artery and from within outward at the proxi- mal end. The suture is then snapped and the other two are placed in a similar manner, after which all are tied and theends left long. If there is no tension the sutures may be tied as placed. While doing this work the fingers and the ends of the vessel are kept smeared with a thin coating of sterile vaseline which prevents the tissues from drying and also fends to retard coagulation. Great care should also be taken not to scratch or otherwise injure the intima in any way as even the slightest scratch means a small clot. The stay sutures being placed and tied, the assistant takes one in either hand atid by gentle trac- tion makes the segment of artery between them a straight line (Fig. 395). The operator starts his con- tinuous suture at one of the stay sutures and con- tinues it with a simple over-and-over stitch to the Fie. 305. — Apposition of the Ends of Divided Arteries by Means of Stay Sutures, Preliminary to Continuous Stitching Together. other, taking care to include all the coats of the vessel in each stitch. It is tied to the second stay suture with a double knot. From sixteen to twenty stitches to the inch should be taken (Fig. 396). The assistant then drops the first stay suture and makes traction on the second and third, bringing this portion of the artery uppermost. The continuous suture is then carried to the third stay where it is again made fast, care being taken not to pucker the vessel. The same procedure is carried out between the third and first stay sutures, thus finishing the anastomosis. The distal serrefine is next taken off and the stitch holes and line of suture are inspected for leakage. There is practically always a slight oozing of blood from the stitch holes which, if the anastomosis has been well done, will stop in a short 661 Arteries, Surgery of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES time if gentle pressure is made; but if there is too much, one or two stitches can be taken through the outer coats of the vessel. The proximal serrefine is taken off last and, after inspection to see that the anastomosis is working properly, the wound is closed. When the ends of the vessel cannot be brought together without tension and it is necessary to graft in a portion of a neighboring vein, the same technique is applied but the grafted portion of vein should be. inserted with the valves pointing in the direction of the blood-current in order that they may not hinder the circulation. The saphenous and the external jugular are the veins commonly available. In Fig. 396. — Stitching Between Stay Sutures shown in Fig. 395. human surgery the autoplastic graft is to be preferred to the heteroplastic graft from animals (Carrel, Guthrie). In performing end-to-end anastomosis between two adjacent vessels, as in reversal of the circulation, they should be divided at different levels to allow for the retraction that inevitably occurs and makes it difficult to approximate the ends if divided at the same level. End-to-side Anastomosis. — The same principles are to be applied in end-to-side anastomosis as in end-to-end. The wound in the side of the vessel being made triangular by the use of three stay sutures, or by the use of light side clamps similar to gastro- enterostomy clamps, the suture may be done as in intestinal anastomosis. If the stay sutures are used they transform the lateral slit into a triangle. In lateral or longitudinal wounds stay sutures may be employed or the suture may be made with the finger passed under the vessel as one would repair a cut in a piece of cloth. When the lateral wound is transverse and embraces more than two-thirds of the circumference of the artery, it is best to complete the division and treat it as an end-to-end anasto- mosis, as the retraction of the edges of the cut makes any other procedure difficult. Lateral Anastomosis. — Bernheim and Stone have described a method of doing this operation, the essential feature of which is to make the wounds in the vessels opposite each other, transverse, and about one-third the circumference of the artery. Retrac- tion of the walls of the vessels transforms these slits into ovals the edges of which are then sutured. Arteriovenous anastomosis, or the reversal of the circulation in an organ or limb, has been proposed for Mime time for conditions in which the artery beyond the point of anastomosis, because of injury or disease, is incapable of transmitting the blood to the part. Frank in 1881 did a series of experiment on reversal of the circulation in animals, none o which were successful; he did not publish them til 1896. The first operation in man was performed by Sai Martin y Satrustegui, a Spaniard, in 1901'* i'l, reported two cases done in the hope of relievini gangrene, neither of which was successful, and late in the same year Jaboulay reported a case also i failure. The operation was first successfully in- formed by Carrel in 1902, and since then has beei done experimentally many times. In 1906 Carre and Guthrie reported thirteen cases with only oni failure, and later reported the result of an autops; at the end of seven months in which the anastomosi was still in good working order. In human beings reversal of the circulation ha been performed fifty-eight times on fifty-six patient (Halsted and Vaughn, 1912). These observers bavi analyzed carefully forty-two of the cases. In thirty one the anastomosis was done for actual gangrene and in eleven for threatened gangrene. Three of th< operations were for presenile gangrene, two in case: of embolism, three for traumatic obliteration, am one in a case of sepsis. Reversal of the circulation in the extremities ha been advocated for presenile gangrene, Raynaud' disease or Judaische krankheit, common senili gangrene, and for the obliteration of the artery by i thrombus or an embolus or an injury. Although there are many cases reported there i. much difference of opinion as to the value of thi operation. Weitung, whose name is intimate! associated with the operation, strongly advocate- it while Coenen and Wirwiorowski after careful experi- mental work consider it unjustifiable and against anatomical and physiological principles. In thi; country Halsted and Vaughn conclude that it b indicated only in traumatic surgery when the arten is destroyed and then should be done simply wit] the object of supplying more blood to the part unti the circulation can be taken up by the collaterals On the other hand, Bernheim (1912) who has hac several cases and has analyzed fifty-two of those reported, considers it a well-recognized operatic-] justified by the clinical results. The experimental and clinical observations are at variance. Carrel showed that in animals the blood pressure in the artery overcame the resistance of the valves in the veins, while Coenen and Wirwiorowski, experimenting on the cadaver, were unable to force the injecting fluid past them. Bernheim ami Weitung take exception to this and say that in life! it is different and the constant pounding of the arterial blood soon breaks down the resistance of the valves as is proved by the clinical results. Halsted and Vaughn conclude that there is enough clinical and experimental evidence to show that the opening is not permanent and that in the few cases in which a thrombus does not immediately form the endothe- lium gradually obliterates the opening, although they admit the operation may be successfully done on animals. They also say that even in the I I where the stoma remains open and the resistance ol the valves is overcome, the blood never reaches the capillaries but is returned to the heart by the anasto- mosing veins. They consider that in only two of the forty-two cases was the circulation enough restore to prevent the progressing gangrene, although local changes showing improvement in the circulation were noted in twenty-three cases. Lejars, in com- menting on Weitung's paper, says that Weitung advocates the operation only in the case of vigorous people with no infection, in whom the gangrene is nol advancing, and he thinks that in this class of cases expectant treatment is usually indicated and is much less dangerous. Bernheim in his analysis of fifty-two cases con- 662 llEKEKEXCE handbook OF THE MEDICAL sciences Arteries, Burger; of iIits fifteen successful and remarks that in the last teen cases reported there were nine sueeesses an. I .,■ failures while the result in one was questionable. 1,11 hen of the patients died immediately after the [,,11 while the course of tin- ili :ea e was uninflu- | in i he remaining twenty-two. i >ne of the chief causes of failure is the poor surgical -k which the average patient who is submitted i" the i. ration presents. Nearly all are old witli existing e which is advancing, and there is often more less infection. The arteries are usually throml >o ed . distance around the gangrenous ana, and in cases the operation is done as a last resort. cases in which the best results have been ob- oe those of " threatened gangrene." Raynaud's ease, Judaische krankheit, and allied conditions, it li pain, cold extremities, and loss of pulse but with- uil gangrene. The other chief cause of failure thrombosis from faulty technic or sepsis, and of the ported cases infection has occurred in an unusually rge number. As to technique, it is impossible for a an who has not done considerable blood-vessel irgery in the laboratory to do a satisfactory anasto- losis on the human with any hope of success. The success of the operation is to be judged by the ■lief of symptoms, i.e. increased warmth, improved lor, relief from pain, pulsation in the vein, and the ■turn of the part threatened to normal. The last word on the reversal of the circulation has nt been said and it is unfortunate that the opinions f good observers are so diametrically opposed. It ould seem to be a justifiable operation in the hands t competent surgeons in certain selected cases and to e of especial value in cases of traumatic destruction f an artery, or where the vessel is plugged by an inhiilus. The operation may also be resorted to with Hue hope of success in certain cases of gangrene, articularly the presenile type, such as Raynaud's isease, be/ore infection or marked actual gangrene as occurred. The technique of the operation is the same as that ~cd in the suture of any blood-vessel. There are nur chief methods: (1) Proximal end of artery to listal end of vein (Carrel); (2) End of artery to side t vein (Weitung); (3) Side to side with ligature of he vein proximal to the anastomosis (Bernheim and 'tone); (4) Anastomosis with a biterminal graft ■.hen there is loss of substance. It has been shown hat a complete reversal of the circulation is unneces- ir\ , it being sufficient to anastomose the proximal end if the artery to the distal end of the vein and ligate the ihcr ends, as the collateral anastomosing veins are ufneient to take care of the return flow of blood. klarked edema of the extremity is usually noted, lowever, after the operation when it is done in this iianner. The Matas Operation fob Aneurysm. — The Uatas operation for the cure of aneurysm was first icrformed by Rudolph Matas in March, 188S, and eported in October of the same year. At the present lay it has replaced in nearly all cases the older opera- ionsof Vntyllus, Hunter, and Basedow. The opera- ion consists in opening the sae under temporary lemqstasis, closing the orifices of all vessels leading it" it by direct suture, and obliterating the sac by Occasionally, in very favorable cases, the trtery may be reconstructed. The object of the oper- itioa is to cure the aneurysm and relieve the pressure on the surrounding parts with as little interference to the circulation as possible. It is simpler and easier o perform than many of the other operations, such as dissecting out the sac after ligature, and has a great advantage in that the artery is controlled in all cases at the point of hemorrhage and not in continuity, thus interfering very little with the collateral circulation and reducing the possibility of gangrene to a minimum. The principle of the operation is as follows: The Fig. 397. — Restorative Operation. The Lembert sutures are closing the single stoma of a sacculated aneu- rysm. sac is regarded as a serous lined cavity the endothe- lium being continuous with that of the artery; this endothelium acts when drawn together and irritated in the same manner as does the peritoneum, and the surfaces unite by the formation anil organization of a plastic exudate. The • list urbance of circula- tion is reduced to a minimum by I he intra- saccular suture of the bleeding points. If the aneurysm is saccu- lar the sac may be ob- literated and the con- tinuity of the vessel restored or, if it is necessary to obliterate the artery, the small- est amount of vessel is destroyed. The col- lapse of the sac, by emptying its contents and its further obliter- ation by suture, re- lieves all pressure on neighboring parts and the satellite vein is not destroyed as is often the case when an at- tempt is made to dis- sect out the sac. The operation is ap- plicable, in one form or another, to all aneurysms except the intrathoracic and abdominal varieties. It should be used in trau- matic aneurysm only after the formation of a true sac and not in the early stages when the tumor is in reality a pulsating hematoma. Arteriorrhaphy, which is an entirely different procedure, should be clone in these cases. There are three types of the operation, called by Matas obliterative, restorative, and reconstructive endoaneurysmorrhaphy. Obliterative Endoaneurysmorrhaphy. — This is the operation applicable in the largest number of cases and is used where the vessel is dilated into a fusiform aneurysm involving all the coats for a varying distance. The opera- tion consists in open- ing the sac and closirg all the openings into tl with continuous su- tures. There are always two openings, representing the main artery, besides a vary- ing number of smaller ones. After closing all the openings the sac is obliterated. Restorative Endo- aneu rysmorrhaphy. — This is the ideal oper- ation but is applicable only in a compara- tively small number of cases. It is used in sacciform aneurysm where there is a dis- tinct sac on one side of the artery communi- cating with the lumen of the vessel by a comparatively small opening. In these cases the opening into the artery is closed with a continuous stitch and the sac obliterated by several rows of sutures. These also reinforce the first suture and strengthen the arterial wall. 663 Fig. 398. — Restorative Operation. The stoma closed. Arteries, Surgery of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES K( c « nst ruct i ve Endoaneurysmorrhaphy. — This method is applicable to aneurysms of the fusiform type where the openings of the parent artery are on the same level, on one side of the sae, and not far apart. The utility of the operation is somewhat Fig. 399. — Reconstructive Operation. Sacculated aneurysm opened and seen from within. Note the opening of a collateral to one side of the main stomata. questioned and it should be used only in very favor- able eases where the walls of the sac are elastic and in good condition, and the danger of gangrene of the part supplied by the artery is great. Since thrombosis is very likely to occur it is of value in these cases as a Fm. 400. — Reconstructive Operation. Aneurysmal sac shown in Fig. 399. Stomata partly closed by Lembert sutures. temporary expedient to supply blood to the part until the development of the collateral circulation. The operation consists in passing a catheter into the two openings of the main artery over which the sac is drawn together and sutured, making a new artery. 664 Technique. — Temporary hemostasis is a necessity and is best obtained by a tourniquet. When this is impossible, as in aneurysm of the iliac or axillary artery, clamps of some form may be applied to the main vessel or it may be tied temporarily with a tape but severe hemorrhage from collaterals entering the Fig. 401. — Reconstructive Operation. Catheter in situ. sac should be expected. The incision should lie made longitudinally directly into the tumor without prelim- inary dissection, the clot turned out, and the walls examined for the openings of the vessels. All of these are closed by an intrasaccular suture. The sutures used are either fine silk, No. 1, or chromic Fig. 402.- -Detail of Reconstructive Operation, being withdrawn. The catheter is catgut, No. 00, on fine straight or curved needles, both sutures and needles being coarser than those used in arteriorrhaphy. The sutures are sterilized in oil and in general the rules applying in arterial surgery are observed, but the operation is less difficult. In the closure of the orifice of the vessel, the suture is REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \rterloflderoslfl arted one-half inch to one side of the opening and deep into the tissues. A continuous over- Id-over stitch is used and in the restorative opera- ,. lumen of the artery is made someM hat smaller ia n that of the original vessel. After the closure "I [ openings the sac is obliterated. This may be , ne in several ways. When opened and the con- iracuated, the sac collapses and forms longi- 1G . 403. Obliterative Operation, Showing Insertion of Second Row of Sutures. udinal folds which are sutured together with a con- inuous stitch. When the sac is small this may be one and the soft tissues and skin closed over it. V lien the sac is large several superimposed layers of uture are used and the skin edges are freed and slid ver (lie unobliterated portion to which they are utured. In certain cases of stiff walled sac which annot be sutured, a skin flap can be slid in and fast- ned in the same manner that skin flaps are used to ate stiff walled cavities in bone. When the sac 1(14. -Detail of Imbricating Stitches for Obliteration of Dead Spaces. is trabeculated and it is impossible to close it at all by suture a part may be excised and the rest packed and allowed to heal by granulation. In post-peritoneal aneurysm, aneurysm of the iliac, the same principle is applied, the peritoneum being used in the same manner as the skin. The results of the intrasaccular operation are very much better as regards cure and freedom from gan- e, than those of the older operation Monod and Vanverts (December, 1911) have collected from the literature L05 cases with the following results: Cures eighty-five (82 per cent i; mortality 11.6 per cent.; gangrene I 9 per cent.; failures 14.5 per cent. The remote results are given in only thirty-seven <>f 1 1,, e cm e and in many I he patienl had been ob- served but a few weei . 01 the twi Ive death . two occurred in eases of aneurysm of the aorta which should not be included in this series. The others 1 i... 403. — Cross-section ol the I issues, Showing Imbrication in the Reconstructive Operation. were caused by shock, hemorrhage, gangrene, sepsis, and pulmonary embolism. The failures consisted in postoperative hemorrhage, of which six cases were fatal, or recurrence of the aneurysm. Presence of a pulse was noted in thirty-five case immediately after the operation, while in others it did not appear for several hours. The results were very much better in long-standing traumatic aneurysm in young people where the vessels were elastic and in good condition, than in the common aneurysm in old subjects. In the former class were seveiitv cases with sixty-one cures, 88.4 per cent, while in the latter class numbering twenty- five, there were fifteen cures, sixty per cent, and twenty eight per cent, mortality. These authors were struck by the large number of postoperative hemorrhages, Fig. 406.- Cross-section of the Tissues in the Obliterative Operation. twelve cases, six of which were fatal. In the recon- structive cases there were twenty-nine per cent, of recurrences. . Matas in 190S reported the results of eighty-five cases and later said he had knowledge of 110 cases operated upon bv his method. Of the eighty-five operations fifty-nine were of the obliterative type, thirteen restorative, and thirteen reconstructive. Of the reconstructive cases, four or 2S.9 per cent. recurred. _ _ Channing C. Simmons. J. Collins Warren. Arteriosclerosis.— See Blood-vessi Is, Pathological Anatomy of, and BloocLpressure. 665 Arthritis, Acute REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis, Acute. — Anatomy. All diarthrodial joints, that is, all joints possessing motion, are bounded by two tissues, the cartilage and the synovia. Under- neath the synovia is the ligament (or fascia), under- neath the cartilage is lymphoid marrow. If the synovia is inflamed, this inflammation constitutes an arthritis. The cartilage itself is probably not capable of inflammation (see Artliritis, Chronic), but an in- flammatory process in the subjacent bone marrow readily finds access to the joint at the circumference of the .cartilage, or even through the cartilage itself by depriving it of its nutrition and so perforating it. Thus a myelitis may easily become an arthritis, and usually does, when the lymphoid marrow is involved. On the other hand, an arthritis starting in the synovia, may involve the marrow by making its way into the bone at the circumference of the cartilage. These two tissues, the synovia and the lymphoid Fig. 407. — Low Power Photomicrograph. Normal capsule of joint, showing smooth surface of synovia above, and the vascular spaces. marrow are the important ones in all cases of acute arthritis. Some diseases affect one, some both. Lymphoid marrow is found in the short and flat bones, in the ends of long bones, and, in children, in the shafts also. It consists of a delicate reticulum of connective tissue in whose meshes are cells of various kinds, and it is these cells which distinguish lymphoid marrow from the fatty marrow of the shafts. Synovial membranes resemble so closely the serous membranes that they are often classified with them. But, although structurally much the same, they differ from the serous membranes in secreting a peculiar fluid — the s\ r novial fluid. In all joints where motion takes place (diarthrodia) a lubricating fluid is neces- sary, and this fluid is furnished by the synovial mem- brane. Every diarthrodial joint is lined with a layer of synovial membrane, except in the places where the articular cartilages are in contact. Here there is no membrane, except at the edge of the cartilages, which the synovial membrane may overlap for two or three millimeters before merging into the carti- laginous structure. Fasciculi and folds of the capsule, the internal ligaments, and fatty internal protrusions are all covered by the membrane. The limits of the synovial membrane an- most easily made out in in- flammation, when a red collarette is seen surrounding the while cartilages. Synovial membranes or synoviie, classed among structures of the lymphatic system, are connective tissue membranes, very thin and delicate, whost limits in health can hardly be defined from the under- lying fascia or ligament. In disease, however, thf membrane may became greatly thickened and have c thickness of perhaps twenty millimeters. In gross the inner surface of a joint presents p smooth and shining surface, interrupted, especially where the membrane folds to pass from one surface U another, by the synovial fringes (plicce sync villous structures of varying size and length, some- what resembling intestinal villi, the largest beine perhaps one centimeter long. They are richly supplied with blood-vessels, for each villus contains thi convoluted twig of an artery. Some of the fringe?, however, are merely hernia-like prolusions into the joint of small masses of fat covered with synovial membrane; these fill up unoccupied spaces. Th; nerves are derived from the same nerve trunks that Fig. 408. — Photomicrograph. Capsule of joint, near a recess showing folds of synovia. supply the muscles of the limb. The nerve fila- ments terminate in small plexuses equally distributed under the synovial membrane. Coloring matter injected into the joint disappears very quickly, to reappear in the lymphatic channels of the limb. Synovia is a clear, alkaline fluid, much like the white of egg in general appearance; when rubbed between the fingers it imparts an oily sensation. It is largely secreted by the cells which cover the -_ vial fringes. In composition it contains albumin, mucin, some fat, leucocytes, and epithelial cells. A fluid identical in composition with synovia can be reproduced by rubbing up a portion of the epidermis is a weak alkaline solution. This fact suggests that most of the mucin is derived from the endothelial cells soaking in the weak alkaline fluid secreted by the fringes, and this view is strengthened by the fact that, when joints are quiet, the synovia in them contains only half as much mucin as when they are iu motion. 1 Etiology. — Acute arthritis may be caused either by injury or by infection, though the propriety of including the first factor as a cause is questionable. However, as a trauma to the lining of a joint ran hemorrhage into the joint itself, and as the physical signs are manifest in the joint, we shall give that phase of the subject a few words, before taking up arthritis proper. 6GG REFERENCE HANDBOOK OF Till'. MKIUt \l. SCIl'.NCF.S Arthritis, Arutc Traumatic Arthritis. — The usual cause is a ,-rench, a "strain," a "sprain," or a dislocation. ures involving the joint form another important , : penetrating wounds of the joint, if absolutely septic, a in it her. If the ligament and with il thesyno- be torn, a greater or lesser amount of blood, and iter of inflammatory products, is poured out into tin' .nit cavity, and it is these that cause the symptoms i thr joint, symptoms persisting until the effusion is orbed and until the synovia is healed. Much the ame may be said of fractures which involve the joint hrough lesion of the cartilages. Morbid Anatomy. — Besides the actual damage of joint structures by the trauma itself, the palho- igical changes are not of great moment. The joint lins the effusion from the ruptured blood-vessels. ably the synovia proliferates somewhat, and the artilage will become more or less fibrillated if the lint be immobilized. Another result of immobili- ation is the encroachment of the synovia on the artilage at its borders. All these changes disappear ipon the healing of the original trauma and the esumption of function. If the joint has been lennanently damaged, as a machine, so to speak, by lie interference with its function from displaced nine fragments, it will be exposed to constant in- even after the fracture has healed. These i. id bone fragments may keep up a continued rritation of the joint. Symptomatology. — Immediately after the injury, or it a short interval of time the joint becomes painful • tiff, and swollen. Motion of it causes increased tain, a id as a rule it contains more or less fluid. Increase of local temperature and reddening may or not be present. Frequently in the case of a torn ligament (or semilunar cartilage in the knee) .! of lmal tenderness may be made out. After i few days or weeks these symptoms subside and leave the joint practically normal. The prognosis is usually good. Except in the knee, whose complicated structure predisposes to a recurrence of the damage, there is little chance of pse. It is to be borne in mind that whatever remains behind after the "synovitis" has run its >e is not due to it but to the injury that caused it. Again, there is little prospect of the disease "running into" anything else. Indeed, some writers maintain that those cases of joint tuberculosis which seem to have been caused by an injury are only lighted up by it. The treatment consists in the first place of hot or cold applications, or of tight compression by bandages and a splint, to restrict the effusion into the joint as much as possible. Afterward rest and support are indicated. Plaster-of-Paris is rarely necessary, nor i- rest in bed. If the joint be properly strapped, so as to exert pressure and to restrain motion, the patient may usually be allowed to go about. Massage and hydrotherapy are excellent in the later stages. Ankylosing Arthritis. — Another form of traumatic arthritis, whose exact pathology is not thoroughly ■ stood, has been described by several writers. 2 After an injury a joint slowly becomes stiffened, until plete bony ankylosis takes place. No fracture ran be demonstrated by the most careful examination. Treatment hitherto has been fruitless. A peculiar deformity sometimes occurring in the spine may be analogous to this. Shortly after a severe injury, a kyphosis makes its appearance, and, if untreated, ly increases. The Roentgen rays show no dis- and no fracture. The treatment consists of a well-fitting plaster jacket to control the increase of deformity. 3 Acute Infectious Arthritis. — Under this head we include every case of acute joint inflammation not falling in the preceding class. The infection may be of the most varied nature. The ordinary pus COCCI may be responsible for it, the pneumococcus, the typhoid bacillus, or the gonoCOCCUS. Some '.'.titers maintain that toxins circulating in the blood ran cause a joint inflammation. Probably acute inflam- Fig. 409. — Low Power 1'nuionu InfectioD — probably gonorrheal — lymphoid elements. •lugraph of a Joint with Mixed showing proliferation of the matory rheumatism belongs in this category, but it will be discussed elsewhere. Penetrating wounds of a joint and infection follow- ing operation cause not a few cases of the disease. As might be expected the disease often accompanies or follows one of the acute infectious diseases, gonor- Fig. 410. — Same as fig. 409; High Power. rhea, pneumonia, typhoid fever, scarlatina, smallpox, and septicemia. Pregnancy and labor favor the appearance of gonorrheal arthritis in women. In the arthritis complicating an infectious disease the microorganism responsible for the joint lesion may G67 Arthritis, Acute REFERENCE HANDBOOK OF THE MEDICAL SCIENCES be that of the disease itself, it may be that of a secondary infection, or it may be mixed. When an arthritis complicates an infectious disease its origin is easily understood, but in some cases the port of entry of the poison, and its appearance in the joint, cannot be ascertained. A sharp dividing line i- not always present between an acute and a chronic infectious arthritis. At the start many chronic joint diseases appear to be acute. On the other hand, the disability and deformity remaining after an acute arthritis must not be confounded with an active chronic arthritis. Pathology. — The three essential tissues in a joint inflammation are the synovia, the marrow, and the deep layer of the periosteum. Sometimes one is involved, sometimes another, sometimes all three. The morbid changes in the bone and in the cartilage are to be regarded as secondary to those of these three tissues. Certain infectious agents seem to have a predilection for one, certain for another of these tissues; thus, the gonococcus affects by preference the synovia, and more rarely the periosteum; the ordinary pus cocci, all three. An arthritis may have its origin in the marrow and spread to the synovia, or the process may be reversed. Occasionally a myelitis of the shaft may spread to the joint, but as a rule the ordinary infectious osteomyelitis of the shaft stops at the epiphyseal line. (Infectious osteomyelitis of the shaft is usually found in adoles- cence.) If the disease start as a myelitis in the end of a long bone, it quickly becomes an arthritis. The ordinary phenomena of inflammation follow the infection, and an exudate is poured into the joint. The disease has been classified upon the basis of this exudate — serous, serofibrinous, purulent, etc. The synovia hypertrophies, thickens, and may undergo a marked villous change. If the infection be a mild one, the exudate may be absorbed after a longer or shorter time and the joint may return to its normal condition. If the infection be more severe, some thickening of the synovia and adhesions in the joint may remain. In the very severe infections the inflammation spreads through- out the joint with great rapidity, killing the bone and cartilage, perhaps bursting through the ligament, and destroying the joint. In certain diseases (e.g. typhoid fever) a marked tendency to dislocation exists. Symptomatology. — Pain is usually the earliest symptom and the most prominent one. It is wont to be very severe and to be increased by motion. It is usually in direct proportion with the severity of the infection. Coincident with the pain appear local heat, swelling, and change of contour. The limb is held in the most comfortable attitude — usually .slight flexion. Fever and constitutional involve- ment are present in the severer forms. Fluid can usually be demonstrated in the joint cavity. In the milder forms the symptoms may soon sub- side. In the severe forms the march of the disease is rapid and alarming, and unless timely treatment is carried out, or in spite of it, the outcome may be fatal. Diagnosis. — The fact that a joint is acutely inflamed is patent to the casual observer. The important fact to be ascertained is as to the character of the inflammation, for upon the early recognition of this may depend the life of the patient. The milder forms of the disease — those that should be treated conservatively, those with a simple serous exudate — are accompanied by few constitutional symptoms or by none at all. The entire trouble is local, and the patient is not sick. The temperature may be slightly above the normal, but not much above it. The severe forms, on the contrary, are accompanied by marked constitutional symptom . as well as by severe local signs — great swelling, pain, heat, etc. An arthritis following typhoid fever may 668 belong in the former class, and by a secondan infection may be converted into one of the latter, The same may be said of a gonorrheal joint and of others. An acute inflammation in one or more joints of an adult always should awaken the suspicion of a gonorrhea. The detection of a lesion in the genito- urinary tract practically clinches the diagn. Often the gonococcus may be cultivated from aspirated fluid, especially in recent cases. Acute inflammatory rheumatism is always fleeting, and its high fever, its acid sweats, etc. If an inflammation remains in one joint it is not due to acute inflam- matory rheumatism. In case of doubt as to the origin of the arthritis, careful inquiry should be made as to the previous occurrence of an acuti infectious disease. Aspiration of the joint will often reveal the pathogenic organism. Scurvy might cause confusion in infants. The history of bottle feeding, the bleeding gums, the exquisite sensitive- ness of a joint, without constitutional or marked local signs, should clear up the doubt. A hemon into a joint, sometimes seen in hemophiliacs, is not wont to be accompanied by many symptoms, either constitutional or local. Tuberculosis is usually slow and chronic. Sarcoma affects the end of one articu- lating bone, but not the joint itself. Treatment. — This depends largely upon the cause and upon the severity of the infection. Milder ta are best treated by rest— weight and pulley extension. splinting, plaster-of-Paris, etc. — by hot or cold applications, and sometimes by aspiration, though this last is not often necessary. In the later sta| massage, passive motion, hot and cold douches, hot air, are all serviceable. In the more severe forms aspiration and washing out of the joint with sterile water, or with a solution of iodine, boric acid, or carbolic acid have been recommended. They should not be continued for long, and too much reliance should not be placed upon them. In the ordinary purulent arthritis, the treatment should be that of any abscess, namely free and early incision, and thorough drainage. Gonorrheal arthritis should be treated locally on the lines laid down. The genito-urinary tract, especially the prostate and seminal vesicles in a man, should also receive attention. Often with the curing of the primary lesion, the joint affection will subside Antigonococcic serum and vaccine are not always oi service, but sometimes their beneficial effect i marked. Leonard W. Ely. References. 1 Frerichs: Wagner's Handworterbuch der Physiologie, iii. f 1, 146. 2. Murphy: Journal of the American Medical Association, April 27, 1912. 3. Mauclaire et Burnier: Archives Generates de Chirurgie, March 25, 1912. Arthritis, Chronic. — The student of chronic diseases of the joints meets at the outset a very perplexing problem. He finds the greatest confusion in all aspei ta of the subject. Various authorities describe different diseases or types of disease under the same name, and the same disease under different names. Many differ- ent classifications have been put forward. One writer holds fast to infection as a cause of certain types, and disturbed metabolism as the cause of ot hers; another writer may reverse these classes completely. Some maintain that all chronic joint diseases arc infectious in their nature. To set forth all the various theories and classifications is not possible lure. Many of them err as being based on clinical data, always an unsatisfactory procedure, others again as based on the Roentgen picture, which can show merely the results of disease. What follows is based mainly upon laboratory study, corrected by clinical observa- REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis. Uiroiilt- ion. li is not all demonstrated truth, bul it is imple, easily comprehended, and, if carefully dige ted, rill furnish' the render with a nidus on which tu n stallize his nun ideas. In order tn avoid hopeless , .nfusiim une must perforce have some such working iasis. Etiology. — All chronic joint diseases whose cause lf know are infectious in their nature, and it seem iesl to regard those whose exact cause we do not know - belonging in the same category. One after another diseases have been placed in it. .Nut long onorrheal arthritis was considered as due to a irritation'' from the urethral mucous tiieni- and joint tuberculosis formed a great mystery uilil its exacl cause was known. Some authorities laim that "faulty metabolism" is a cause of some but faulty metabolism in a joint is the result of , not its cause. It is present in any di i An increased excretion of lime salts has been I in the urine of some patients. This is, of what one would expect with a rarefying isteitis. Various observers (Schiller, Banantyne, Fayer- eather, et al.) have isolated pure cultures of bacteria rom certain cases of chronic arthritis, and, because iese bacteria are not always identical, doubt has been hrown upon the result of the investigations. It vere better to regard them as authentic, and to con- lude that different organisms are capable of pro- lucing the same joint changes, or changes which, in he present state of our knowledge, appear the same. < Ither investigators have been unable to obtain any lacteria from these chronically inflamed joints, but he organisms may be there, nevertheless. One must iear in mind that until recently the Spirochwta escaped recognition, and that it is often lillieult to find tubercle bacilli in tuberculous joints. Igain, if the organisms are in the bone marrow nay easily escape detection. In many of these patients a possible source of nfection has been found, and, when this was removed, ase died out or became quiescent. Diseased onsils, a purulent otitis, or nasal sinusitis, an intes- mal indigestion, a suppurating tooth cavity, a yphilitic or gonorrheal infection, have all been linked i]) in this way in a causal relation to the di ease. >i casionally one obtains a history of a severe attack if "dysentery" which immediately antedated the ymptoms. The more thoroughly one searches the ii tory, the more often will one find evidences of an nfection, so often indeed as to render improbable the elation of coincidence, and to make the causal rela- iOD almost certain. No age is exempt except the earliest infancy, 'orae types are found in the earlier periods of life nost frequently, and other types in the later periods. Mental emotion is thought by some to stand in a ausal relation. This is possible, but the relation is irobably not a direct one. If we regard intestinal lection as a cause of the disease, we can easily see tow mental emotion might predispose by disturbing he digestion. It is not likely that occupation is a factor. Chronic irthritis affects the rich and the poor, the hard- working and the idle. cently the influence of the ductless glands — thyroid, pituitary, suprarenal — has been I 'bated, but nothing has yet been established. I tic thymus gland particularly has been held responsi- ve, and the administration of its powdered extract has been recommended in some cases as a cure, but i I ick of the secretion of a gland which normally has ed to functionate can hardly be regarded as a cause of the disease. Finally, let it be said that certain of the changes occurring in some types of the disease are analogous to those often taking place as age advances. Indeed, the nodes found on the terminal phalangeal joints— Herberden's nod.- are aid to !»' an evidence of longevity. Beitzke in a series of consecutive autop- found localized ero ion ol the cartilage in a very large proportion. 8 Classification. — It is manifest that if our theory of t he infect ions nut ure of every case of chronic art hri- tis is correct, no form of classification we 'an adopt will stand until we liml out everj infection that will cause the disease, and i he exact pathological changes that each causes. This we have doni 01 i i g in tuberculosis, but not in all, and our task will not be lightened by bestowing meaningless and im terms such as arthritis deformans, rheumatoid •<• tie, metabolic arthritis, etc., upon the whole class or u I ion certain divisions ol it . For the present it seems wiser, if possible, to classify upon a pathological basis, and this we can do. All, or almost all, cases of chronic arthritis fall into one of two I ipe, and while some present the char- acteristics of both types in t he same joint or in differ- ent joints, the preponderance oi Set of changes is usually so great as to leave no doubt as to the type in which the joint should be placed. In our study of joint diseases we come to deal with five tissues, namely the red or lymphoid marrow and the trabecular in the ends of the bone, the articular cartilage, the synovia, and the ligament. The marrow consists of a delicate reticulum of connective tissue and fat, in whose meshes are many cells of various kinds. It is these cells which distin- guish the marrow in the ends of the long bones of adults from that of the shafts. In children the marrow in the shafts also is of the lymphoid variety. The custom has been to regard the marrow as more or less of a "filling" for the bones and of compara- tively slight importance in bone diseases. On the contrary, it is probably the tissue of prime importance in all bone disease, as can be seen by a study of specimens under the microscope. From the marrow the bone trabecular derive their nutrition (they have no blood-vessels of their own) and any changes in it are reflected in them. A mild irritation in the marrow is wont to cause an hypertrophy of bone, a stronger one, an atrophy, and a severe inflammation results in death of the bone. Certain forms of degeneration of the marrow, as we shall see, are also follow-ed by an hypertrophy of bone. Various authors have mentioned the marrow changes in bone disease, but as a rule have failed to attach much importance to them. All bone tissue is the same, and that in the ends of the long bones and in the short and Hat bones — can- cellous bone — differs from that in the shafts — compact bone — only in its arrangement and in its amount. Bone is not subject itself to inflammation, or directly to disease. The changes in it simply reflect the pro- cesses in its contained marrow. The trabecular be- come thicker and more numerous from the action of -mall round cells called osteoblasts, that may be seen under the microscope lining their surface — produc- tive osteitis. The bone atrophies by the action of osteoclasts, giant cells, which lie in small excavations in the trabecular — Howship's lacuna'. This form of absorption of the bone is known as rarefying osteitis or rarefaction. Again, the bone may atrophy by the absorption of lime salts. The articular cartilage, like the bone, is a connec- tive tissue structure, and like the bone again, has no blood-vessels, but draws its nutrition from the sub- jacent bone marrow, and, to a lesser extent, from the synovia, with which it is continuous at its periphery. The transition from the structure of the cartilage to that of the synovia is a gradual one, and immobiliza- tion causes an encroachment of the latter on the former. When motion is resumed in the joint the cartilage again pushes out its borders. Lack of 669 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES motion is said to be the cause of the fibrillation one often sees in the cartilage of diseased joints. Possi- bly this fibrillation may also be caused by the inter- ference with the nutrition of the cartilage by disease in the subjacent marrow. A proliferation of the bone marrow causes an atro- phy of the cartilage, and sometimes an erosion, but the cartilage is never attacked by diseases from the joint side. An exudate in the joint is without effect, on the structure of the cartilage. The precipitation of "layers of fibrin," if it exists, is not of great importance. The synovia, a connective tissue structure, lines the joint except that part of it formed by the articular cartilage. It is a delicate membrane consisting of a single layer of cells, and produces the fluid which lubricates the joint. Its reduplications, folds and villi, are said to be in direct proportion to the amount of motion required of the joint. In inflammations the synovia usually proliferates and be- comes thickened, spreading out over the cartilage, and partially hiding it but seldom if ever, becoming attached to it. As the mem- brane proliferates, it encroaches on the substance of the cartilage at its per- iphery, and often causes an erosion of it, but it is probably true that no amount of proliferation or disease in the syno- via avails to dam- age the cartilage from its joint sur- face. There is a sort of reciprocal rela- tion between the synovia and the cartilage where they meet at the circum- ference of the latter: as one advances the other recedes. Hy- pertrophy of the one is followed by atrophy of the other and vice versa. The ligament con- sists of bundles of fibrous tissue, and is continuous with the superficial layer of the periosteum. The deep or cellular layer of the periosteum, on the contrary, par- takes more of the nature of the subjacent bone marrow and seems to be affected by the same diseases. In the study of joint diseases the bone and cartilage have hitherto received most attention, but with confusing results. It is probable that these two tissues play a passive role in all joint diseases. They form the '"stroma" of the joint, so to speak. For a better understanding of joint disease we turn to the active tissues — the "parenchyma" — and these the synovia and the lymphoid marrow constitute. If we focus our attention on these two tissues we can compre- hend the changes in the others, and upon the changes in these two we base our classification, dividing all chronic joint diseases into two main types: Type I. Cases characterized by a proliferation of th^ synovia or of the lymphoid marrow, or of both, with a resulting atrophy of bone and cartilage. Type II. Cases characterized by an inflammation 670 Fig. 411. — Bone Tuberculosis. Note the two isolated tubercles (n), surrounded by apparently healthy marrow. They are merely a part of an extensive disease in the bone. This photomicrograph shows well the futility of attempting to eradi- cate the disease with a curette. The ordinary bone curette, magnified propor- tionally, would be about as large as a shovel. and degeneration of the marrow and synovia, with a resulting hypertrophy of bone and cartilage. Under the first heading we place tuberculosis the 'various forms of chronic synovitis of obscure origin, intermittent hydrops (probably), syphilitic synovitis, Still's disease, and that large group of cases known by various names by different writers— the atrophic arthritis of Goldthwait, the proliferate e type of Nichols and Richardson, the rheumai arthritis of the English writers, etc. The second group includes those cases variously known under the terms osteoarthritis, hypertropl form (Goldthwait), degenerative form (Nichols and Richardson), etc. In this group would be placed Heberden's nodes, also morbus coxa? senilis, and probably Charcot's joint. Type I. Tuberculosis. Etiology. — The disease is caused by the tubercle bacillus, which is brought to the joint ale invariably in blood stream, ac- cording to our present knowledge. Autopsies show in the great majority of cases some otli r tuberculous foi in the body. En- vironment and heredity play the same rule here as in tuberculosis of other organ-. Trauma is decidedly subsidiary as a cause. It may be responsible to a cer- tain degree in an occasional case of synovial origin, but even here its action is probably that of lighting up a latent disease. The trauma is a strain or a wrench. Frac- tures and disloca- tions are not fol- lowed by tubercu- losis. Anon-tuber- culous inflamma- tion does not "run [ into" a tubercu- lous one. The dis- ease is much more frequent in child- hood than in adult life. The reason for this we shall presently see. The two sexes are about equally afflicted. Roughly the joints may be said to be affected in proportion to their size. The sacroiliac joint forms an exception to this; disease of this joint is rare. Various observers differ in their estimate of frequency of involvem of the various joints, but following is the appoximate order: Spine, hip, knee, ankle and tarsus, \vri>t, shoulder, elbow, fingers. Other joints are rarely involved. The question as to the relative number of cases caused by the bovine and by the human type of tubercle bacillus is not yet definitely settled. Some writers maintain that the bovine type is responsible for the great majority, others deny this. Pathology. — The primary focus is always locate.] in the synovia or in the lymphoid marrow, and at no time are any other tissues directly involved, so long as the infection is a simple unmixed one. The d layer of the periosteum forms an exception to this REFERENCE HANDBOOK OF THE MEDIO \ I. SCIENI ES Arthritis, i In. ,i,l. In all bone diseases this layer seems to lake of the nature of the subjacent mar- aud to !"• vulnerable to the same dis- When we speak of the marrow here- rv, i es. jjer this layer of the periosteum is to be i luilecl. The disease may remain indefi- elj in its original seat, or it may spread I ,,i' the synovia to the marrow or from the to the synovia. .Many authorities , :,,, thai the primary affection is often by a tuberculous plus in an end This may be so in some cases, but it is rare. infection here, as in most organs in is by a bacillus or by several I illi that are thrown out from the blood earn. This brings us to the vexed ques- . by tuberculosis occurs in the region lints and not in the shafts of the long les. Tuberculosis is essentially a disease ymphoid tissue (endothelial and epithelial also) and ill the region of the joints two lymphoid tissues, the synovia red or lymphoid marrow. When 30 two tissues disappear from the joint el a bony ankylosis, spontaneous or oper- jve, the disease disappears, provided (vays there has been no secondary infec- | n. If a secondary infection be added, the : 'I'bid process may attack other tissues pre- msly invulnerable. This is why tuber- affects children more often than : ults — their bones contain more red mar- a. The synovial form is comparatively H2. — Bone Tuberculosis, Showing the Spread of the Tubcr- 'rocess under the Periosteum and Cartilage; Specimen from the xternal Condyle in a Twelve-year-old Child. The joint is not yet I; X 8 diameters A, Articular cartilage; B, epiphysis; C, )iphyseal line; D, periosteum; E, area of tuberculosis. Fig. 413. — Tuberculosis of Boue Marrow at Margin of the Articular Cartilage. rare in children, but much more frequent in adults, but again in infants, whose bone ends are com- posed mostly of cartilage (immune to tuberculosis) Rovsing declares that the disease is always synovial. The shafts of children's bones contain red marrow. Various observers have described primary tubercu- losis of their long bones. It will simplify our com- prehension of tuberculosis of the bones if we regard it, not as an osteitis but as a myelitis. Tuberculosis exists in bone but not of it. Let us briefly' trace the disease from its start, taking up first the cases with a bony focus, and then those with a synovial. The tubercle bacilli in the marrow cause a certain reaction of the tissues, which results in the formation of the characteristic tubercle, with its tendency to break down at the center and to spread at the periphery. On the other hand, nature strives to wall off the disease by the production of fibrous tissue and by the strengthening of the bone about the tuberculous area, and according as one process or the other is more active, the disease tends to spread or to be circumscribed. New tubercles form in the marrow, spreading in all directions, and coalescing. Away from the joint the disease may extend as far as the lymphoid marrow extends, out- ward to the periosteum, and toward the joint, to the cartilage. When the tuberculous granulations reach the periosteum, they are arrested, and must turn aside to follow along underneath it, in its deep layer. In this ray they may reach the joint and break into it. Very rarely they break through the periosteum, and never reach the joint. When the tuberculous granulations make their way to the cartilage, as they usually do, they interfere with its nutrition. The cartilage degenerates, either in a small spot, or, if the spread of the granulations under it has been rapid, in a wide area. This degeneration of the cartilage permits the disease to reach the joint, but a normal cartilage is a bar to the disease. In children the march of the granulations is arrested, for a time at least, by the epi- physeal cartilage. The primary focus may C71 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES be located on either side of this cartilage. Stiles of Edinburgh maintains that it is always on the "shaft side," in what he aptly terms the metaphysial We see, then, that the joint may be involved either at the periphery of the articular cartilage or through an opening in the cartilage itself. When the tuberculous Fig. 414. — Lifting off of Cartilage. Disease of subjacent bone marrow. The cartilage near the joint surface has undergone fibrillation. This is probably what has been mistaken for fibrin. granulations have reached the joint, they infect the synovia, and now, instead of a simple tuberculous myelitis, we have a tuberculous joint. Previous to the irruption, the joint may have been the seat of a serous exudate. The next step is usually the involvement of the other bone of the joint, and the attack must be made at the periphery of the cartilage where it joins the synovia, for, as normal cartilage is a barrier to the disease, and as the cartilage of the other bone is until now normal, the disease must make its way into the bone where it is not protected by cartilage. When the tuberculous granulations have made their way into the other bone, the morbid process is repeated in it. The granulations in the marrow interfere with the nutrition of the bone trabecule and kill them as they do the cartilage. Sometimes one may see evidences of a productive osteitis in the neighborhood of the disease, but the essential process is a rarefaction, and an "eating away." If the spread be rapid, the bone may be killed in large pieces with the formation of sequestra, if slow, then in small pieces — bone sand. The cartilage, as it degenerates, becomes fibrillated. Under the microscope the tuberculous granulations can be seen pushing their way up through it. A quite characteristic picture is that of a thin layer of granulations pushing their way along immediately under the cartilage, but, in the early stages, showing no tubercles. We have never been able to identify the "layers of fibrin" described by some authors as precipitated en the surface of the cartilage, and doubt i heir existence. The synovia when attacked becomes thickened and is often thrown into folds. It tends to spread 672 out over the cartilage and to hide it, especially at tin margins. It encroaches on the cartilage, but prob ably does not often become adherent to it. Tin characteristic change in the synovia is a villoui hypertrophy, seen by the naked eye, and ven beautifully under the microscope. Instead of thi membrane consisting of a thin delicate lavei of cells, hardly distinguishable under "thi microscope from the fibrous connective tis^n. beneath it, it attains an appreciable thick ness, perhaps up to a quarter of an inch. lik. moss on a rock. In the substance of thi membrane the tubercles may be seen. « acute inflammation. Again, at any time before secondary infection takes place, the contents may be absorbed and the abscess may spontaneously disap- Fig. 415. — Whin- Swelling; Small Focus in Upper Epiphyseal Line of Tibia. Synovitis of joint, but no tuberculous process aparl from the focus as noted; a, epiphysis; >>, primary focus; c, shaft. (Nichols.) REFERENCE HANDBOOK OF THE MEDICAL SCIENt I S Arthritis, Chronic ,. a r. The walls of an uninfected tuberculous abscess ,-,'• composed of the necrotic tissue of the structure in hich it lies. The walls of an infected abscess are ijckened, porky, suppurating, and contain tubercles. fter an abscess has opened spontaneously or as been opened by the knife, it almost invaria- K becomes secondarily infected. . ,dies. — These are small, hard, slippery, nooth, shiny bodies resembling melon seeds, uiue- found in tuberculous joints (and mi sheaths), especially in the synovial forms f relatively benign course. Their origin has disputed. In one joint, evidently diseased I years before, I found a collection of them acked in a capsule, like the seeds in a pome- ranate, and from study of this unique specimen, am inclined to regard rice bodies as the result urative process of nature which walls off ..m lenses the tuberculous granulations. — As has been said, nature attempts to ure a tuberculous joint by walling off the gran- lations with fibrous tissue, and in the bone by ing the bone trabecules and by the forma- new trabecule. This process often goes and in hand with the extension of the disease. i- therefore inexpedient to attempt the divi- m of the disease into periods of invasion and The damage often is spreading in one if the joint, and is undergoing repair in tiother part. It is seen also that whereas rare- iriiiu, is the characteristic change in tubercu- ius bone, the process of repair will cause areas tdi nsation of bone. In children complete cure is probably possible ith good function. Fibrous ankylosis, or, arely, bony ankylosis, may be the outcome. (.my ankylosis only occurs after a secondary ifection, or after operation. In adults cure without radical operation, except perhaps in the mild ynovial forms, never takes place. Function is badly damaged in adults, and bony ankylosis ever occurs, except after operation. tilled with necrotic material, especially directly beneath the cartilage. It may cut easily with a knife and float, in water, or it may be denser than normal. Drops of fat may follow the saw on section — Fia. 416.- -Fibrillation of Cartilage; Granulation Tissue Pushing its Way Through. The net result, of a tuberculosis may be summed up as follows: The bone contains grayish or yellowish ireas surrounded by hyperemic zones. It has a worm-eaten appearance, and often presents cavities Vol. I.— 43 Fig. 417. — Entire Thickness of Tuberculous Synovia — 40 mm. objective. fatty osteomalacia. The cavities may contain sequestra; abscesses may be found in the joint or near it. The cartilage is degenerated and eroded. In bone cases the erosion is often located near the center of the cartilage. In fairly early synovial cases, the erosion may be mostly at the periphery. On the other hand, when a badly diseased tuber- culous joint (synovial or bony) is opened for inspection the cartilage may appear practically normal. The joint cavity may be the seat of an abscess or may contain one of several kinds of fluid, or it may have practically disappeared, leaving little else than a mass of fibrous adhesions binding the ends of the bones together. The synovia may be thickened and succulent, or fibrous and dense. It may present villous hyper- trophy or not. Cheesy tubercles may be evident to the naked eye or they may not be evident. The secondary effects of the morbid process in the joint upon the rest of the limb are marked. Although a slight primary lengthening may be perceived by careful measurement in a growing child (due to the stimulation of growth by the irritation near the epiphyseal line) this soon gives place to a shortening. All the tissues of the affected limb are atrophied and ill-nourished. Symptoms and Physical Signs. — A thorough knowdedge of the morbid process in joints enables one to foretell with a fair amount of accuracy what the symptoms and physical signs will be. The inflammatory process in and about the joint causes pain. Nature attempts to place the joint at rest by tightening up the muscles — muscular spasm. The inflammatory products, the pain and the muscular spasm cause limitation of motion and often a fixed position in the most comfortable attitude of the joint — usually semi- flexion. From these factors result disturbance of func- tion, and muscular atrophy. If the joint be superficial, change of contour, sensitiveness to pressure, and in- creased temperature may be perceived. If fluid be 673 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES present in the joint it can be detected by palpation, abscess formation also. Constitutional involvement and secondary infection will give their peculiar signs. Amyloid degeneration of the viscera sometimes follows prolonged second- ary infection. Deformity is the sum of the muscular spasm, the inflammatory products, the muscular atrophy, and the change in contour. Pain is almost invariably present in some degree, and varies from a slight pain upon use to the most agonizing paroxysms. It is greater in the bony than in the synovial type, and is usually worse during the forma- tion of an abscess, while the contents are under tension. The pain is often peculiar during the earlier stages of the disease, by reason of its presence in the morning when the joint is first being used, wearing away during the day. Again, the pain may come on during the night when the muscular spasm relaxes, waking the patient up, often with a cry — the notorious "night cry" of tuberculous joint disease. The pain may be felt in the joint itself or at a point some distance off, whose nerve supply is the same as that of the joint — referred pain. Thus, in hip-joint disease the patient for a long time may refer his sensation to the knee, or, in disease of the spine, to the lower ex- tremities. Muscular spasm is an early physical sign and a most important one in the diagnosis. It is greater in the bony forms of the disease than in the synovial, and is to be viewed as a conservative process of nature — an at- tempt to put the joint at rest. It is well brought out by attempting to put the joint through its arc of motion. All muscles passing over the joint take part in the .spasm. ankylosis, and is wont to persist even after the dis ease is cured. If due to muscular spasm it disappear; Fig. 418. — Tuberculous Synovia, Showing Well-marked Effort at Encapsula- tion of the Tubercles — Discrete Tubercles. Limitation of motion is also an early sign, varies from a slight limitation at the extremes, to a complete Fig. 419. — Synovial Tuberculosis, with Little Tendency to Encapsulation. on the administration of an anesthetic, but not il due to inflammatory products. The change in attitude is more or less complex ii its causation. It is partly due to thi mechanical effects of the inflammatory products and partly due to the muscuiai spasm. The most logical explanation ol the muscular factor has been set forth by Mark Jansen. 4 Jansen reasons that th< muscles that pass over the diseased join' alone are those which often give it it- early attitude. These soon atrophy, and then the attitude is determined by the polyarticular muscles. Disturbance of function of course mani- fests itself in various ways. If the upper _ extremity be affected the patient will be awkward in its use, and will use the other vicariously; if the lower extremity, he will limp. Very young children may refuse to use the diseased joint at all. Muscular atrophy of a certain degree would naturally be expected in a limb which is put more or less at rest from any cause, but the degree of muscular atrophy which accompanies tuberculous joint dis- ease, especially the bony type, is greater than that of any other, and has never been explained satisfactorily. It is so charac- teristic a sign of this disease that its pres- ence should always be sought carefully, by comparing the actual circumference of the limb above and below the joint with that of the opposite limb. A tape measure is re- quisite for this. The eye is not reliable enough. The difference in the circumfer- ence of the two limbs may amount to two or three inches. The bones of the affected limb after a while lag behind in their growth and are not only shorter than on the normal side, but atrophied as well. 674 REFERENCE HANDBOOK OF THE MEDICAL 8CIENCES Arthritis, ( lirnnlc Change of contour will usually be easily dc- i,,l in the superficial joints. The normal mcavitii's will have disappeared, and .swelling ,,ften present. Of ten the bones look enlarged, ii this enlargement is only apparent, and is due , the atrophy above and below the joint, and. in Id oases especially, to the shrinking that ensues , the contraction of the new fibrous tissue. welling Of some degree is almost always present the early stages except in the shoulder. In ie limbs the swelling is often distinctly fusiform. aess to pressure and increased tempi ra- often significant. The sensitiveness may e localized or it may be present all about the Fluid is often present but not always. A " infiltration is more frequent. Abscesses , 'bin' the joint and without it, will give signs f fluctuation. The character of fluid in the lint cannot be told without aspiration. \ peculiar appearance of some tuberculous lints, especially of the knee, has given a name to his disease — white swelling. It is frequent in with a profuse proliferation of the synovia. lie so-called fungous type. Swelling is marked osiform, the skin is pearly white, the veins re dilated. Constitutional involvement may be due to econdary infection with pus germs. Fever and maciation may then be marked. Tuberculous in ningitis is a fairly frequent complication, dly in children, and is invariably fatal. Pulmo- iary tuberculosis is frequent in adults. Poncet describes a disease which he terms "tuber- ulous rheumatism," due probably to the action of Fig. 420. — Tuberculosis of the Elbow; synovial type, showing the tuberculous process making its way through the periosteum into the bone under the margin of the articular cartilage. Section through the corouoid process ; X about 20 diameters. Flo. 421. — Portion of Wall of Tuberculous Bone Cavity. "attenuated bacilli," but in spite of great insistence, he has not yet succeeded in establishing the truth of his position. Under the head of symptomatology it is proper to mention also the reaction that patients with tubercu- lous joints give to the various tuberculin tests, and to describe the appearance of joints in a Roentgen picture. The tuberculin tests are suggestive but not con- clusive. Usually a patient with a tuberculous joint will react, but not always. Again, patients with non- tuberculous joint lesions may give the reaction. A skiagram of a tuberculous joint may or may not be very valuable. If it shows anything it will show the lesions characteristic of cases in Type I of the chronic arthritides, and these are: a thickening of the synovia, a rarefaction of the bone, and a thin- ning of the cartilage. Old cases may show areas of thickened bone. Rarefaction of bone appears as dark areas in the plate, thickening as light areas. The cartilage sometimes disappears, but more often is present in spots, though thinned. The bone has a "worm-eaten appearance. The diagnosis is to be made on the basis of a chronic disease with characteristic symptoms and physical signs, and upon the Roentgen picture. These will evidence a lesion of type I. If the lesion be uniarticular and if the tuberculin test be positive, the joint is almost certainly tuberculous, especially if the patient be a child. The injection of some aspi- rated fluid into a guinea-pig is a most valuable aid. In the past a tendency has existed to call every chronic uniarticular joint disease tuberculous. This is an error and is responsible for many therapeutic systems. No pains should be spared in making a diagnosis that will stand the test. A careful history is essential, and the patient should be stripped, if a man or a child. If the patient be a woman, access to most regions of the body is possible, and the history should bring out any essential matters of disease in the others. Differential Diagnosis. — From other uniarticular diseases in type I joint tuberculosis may be ex- tremely difficult to differentiate. Often a number of examinations may be necessary at intervals of two or three months. In the meantime the joint should be immobilized if the bone be affected. The tuberculin 675 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tests are suggestive, the animal test may be final, if fluid can be drawn from the joint. Cold abscesses or tuberculous sinuses will clear up the case. A piece of the wall of an infected sinus will show tubercles under the microscope In the spine an angular kyphosis occurring in a chronic joint disease means tuberculosis. Secondary infection never occurs in the other diseases of this type. In children the chances are heavily in favor of tuberculosis. Often evidences of the specific infection of other disease may be detected, such as gonorrhea. A uniarticular arthritis of type II may simulate tuberculosis, especially in the hip, but the obstruction to motion is mechanical, and not due to muscular spasm. The x-rays show a production of new bone and cartilage. Syphilis is wont to affect the shafts. If it affects the ends of the long bones, the joint is seldom if ever involved. A form of synovitis is occasionally met in tertiary syphilis, which resembles synovial tuber- culosis. The patient will show a reaction to the Wassermann or Noguchi tests, and will quickly react to antisyphilitic treatment. Sarcoma may be located in the bone end, but does not affect the joint itself or the other bone. Fractures occur frequently, and the Roentgen picture reveals a growth on the bone, or a destruction of large masses of it, not the "worm-eaten" appearance of tuberculosis. Charcot's joints are practically painless. In them disorganization is evident but not inflammation. Masses of loose bone and cartilage can be felt in the joint, and appear in a skiagram. Evidences of a cord lesion can be easily made out, if sought. Tuberculous joints are often treated for long pe- riods under a diagnosis of rheumatism, but the diseases are so different that the mistake is inexcusable. Acute infectious arthritis (suppurative) accom panies one of the acute infectious diseases, such a Fro. 422. — Uninfected Tuberculous Sinus. No tubercles were found in the walla of this sinus, but the joint from which it came was demonstrated to be tuberculous. Fig. 423. — Cross Section of Old Infected Tuberculous Sinus, Showing Tubercles in the Walls. Contrast with Fig. 422. scarlet fever, pneumonia, and typhoid fever, or follows it shortly. It occurs also without antecedent disease. The acute nature, the pyrexia, great pain, leucocytosis, and early abscess formation will dis- tinguish this disease from tuberculosis. Gonorrheal arthritis is usually acute in its onset, and is accompanied by great pain and swelling. When the disease has run its course, the joint is left more or less damaged, but w-ithout active symptoms. The history and the examination of the urethra and the urine are most important. Scurvy comes on acutely, especially in bottle-fed children, and is accompanied by great pain and sensitiveness of one or i more joints. The child cries on being moved, and may have swollen, bleeding gums. Fruit juice internally causes a rapid abatement of the disease. Joint tuberculosis in children is rare during the first year, the age when scurvy most often occurs. Symptoms of fracture in the neighbor- hood of a joint follow immediately on an injury or at a very short interval. The skiagram is most important in the diag- nosis. Sprain. — Frequently a child is seen who complains of pain in a joint, and shows marked limitation of motion in it. A diagnosis is not always possible at the firs; examination, but if the joint be immobilized the symptoms disappear, and force the conclusion that a sprain or a wrench was at the bottom of the trouble. Hemarthrosis. — The patient will com- plain that on one or more occasions one or more of his limbs has been greatly swollen, without any known cause, and usually without much pain. An examination 67G REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis, ( (ironic iows marked swelling and a large amount of fluid in ie joint, but no muscular atrophy nor spasm. A ireful questioning will brine out the fact that the t is a "bleeder." In the later stages the absorption of the fluid, the joint he seat of dense fibrous adhesions. Hysterical Joints. — A marked dispropor- m is present between the subjective and ie objective symptoms. A certain amount dstance to motion, but no true muscu- -m is present, and the resistance dis- iU the patient's attention be diverted. jperficial sensitiveness is often present, and ysterical stigmata. No definite anatomical ran be detected. A diagnosis of ysterical joint should never be made until id examinations have failed to reveal " al pathological change. Prognosis. — In general this may be said to e good quoad litam, but bad so far as func- concerned. A joint tuberculosis ithout secondary infection presents no nmediate danger to life, but we must not irget that the presence of the disease in lie joint shows a vulnerability to tuber- and a probability that some other sists in the body. The chief dangers berculous involvement of other organs lungs, meninges, etc.) and secondary infec- ion. Abscesses always make the prognosis but if they can be kept from ruptur- hey rarely do much damage, except in he spine. Tuberculosis of the lungs or of the men- nges carries off many patients even after lealing of their joint lesion. Secondary nfection is always a dreaded complication, tid adds greatly to the danger. Amyloid {(•generation is almost invariably fatal. Tubercu- ■ sis of the spine is more serious than tuberculosis >f the smaller joints. Tuberculosis of the sacro- liac joint is usually fatal. As to function, this may are wont to recover with better function than the larger. In adults spontaneous bony union never occurs, and a movable Joint seldom if ever, fibrous Fig. 424. — Rice Bodies In their Capsule. 40 mm. objective. vary in children from good motion to complete ankylosis, according to the location of the disease, and the efficacy of treatment. The smaller joints Rice Body. Zeiss objective aa. ocular 3. ankylosis is the rule with them. In adults Pott's disease always has a bad prognosis, especially if any destruction of bone has taken place. Constitutional Treatment. — We must keep in mind always that the joint tuberculosis as a rule is a comparatively harmless local manifestation of a very serious constitutional disorder, and that while we are giving the joint its proper local treatment, we must at the same time endeavor to treat the patient himself. We therefore insist upon fresh air all the time, and upon plenty of nourishing food. The patient should live out of doors, and sleep out of doors except in the bitterest and most inclement weather. If this be impossible, his windows should be wide open day and night. Sun parlors are an abomination. The child is better off in a tenement than in the wards of the ordinary hospital. The influence of climate does not seem as important as in pul- monary tuberculosis. It is doubtful if any climate is specific. Many of the younger patients do well at the seashore, but possibly this is be- cause most children thrive at the beach. I doubt if the course of the disease is shortened there. Drugs are of little use in the disease. Cod- liver oil is a well-tolerated form of fat for the winter months. The bowels should move regu- larly, of course. The mouth and teeth should be kept in good condition. The tonsil is consid- ered to be a frequent port of entry for the tuber- cle bacilli. Therefore enlarged tonsils should be enucleated. Occasionally tuberculous nodules will be found in them, especially in the medium sized, tough ones. Adenoids also should be re- moved. Frequently these operations will have a favorable effect upon the cervical adenitis often present in children. Although the statement may sound heretical, I believe that radical opera- tions for cervical adenitis in children are rarely in- dicated. Without wishing to seem jocular, I think 077 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES they are like the attempt to kill a dog by cutting off his tail. Local Treatment. — If we have properly digested the morbid anatomy of joint tuberculosis we have perceived two things; first, that the entire patho- logical process may be interpreted as an effort of nature to deprive the joint of function, and second, that the uncomplicated disease is strict ly localized, affecting but two tissues, namely, the synovia and the lymphoid marrow, but that when secondary infection has been added other tissues are involved, and the danger is greatly increased. From these facts we draw our two main rules of treatment: (1) deprive the joint of function; (2) avoid secondary infection. Certain other facts should stand out also. Cure of tuberculous joints in adults is very rare under conservative treatment, if it ever occurs. The best that can possibly be attained in them is a stiff joint under any form of treatment. Radical treatment cures the disease in a few months, while conservative treatment, granting that it ever cures, takes years. Therefore, we say that the treatment to be pursued among adults is almost invariably radical, and the object of the radical treatment is to destroy function in the joint. The red marrow and the synovia owe their presence in the joint to function. If function be destroyed they disappear, if they disappear the disease dies out. There can be no joint tubercu- losis where they are not. The disease gets well because it has no food. It is starved out, so to speak. If this destruction of the joint cannot be done, then the operation must be planned to re- move every particle of infected tissue. We modify this rule of radical treatment by the statement that, as the diagnosis is often uncertain, a six months trial of conservative treatment is advisable, and that, if secondary infection is present, a vigorous effort should be made to overcome it before proceed- ing to operation. Among children the case is different. In their children have red marrow in their bone shafts. Henet to destroy the joint in them is not necessarily to curt the disease. Again, radical operations on children's joints, bj Fig. 426. — Section through Rice Body. Zeiss objective C. joints conservative treatment often yields good function, and frequently cures the disease. Radical treatment, even properly carried out, often fails to cure, and the reason of this is that, unlike adults, 678 Fig. 427.— Old Calcined Tubercle in Bone. interference with the center of growth, cause a marked lagging behind in development, and a resulting deformity of great degree as the child grows up. The treatment of joint tuberculosis in children, therefore, is almost invariably conservative. We follow it in the face of all obstacles until all hope of saving the child's limb is gone, or until amyloid degeneration begins, and then we amputate. In adolescents the treatment is as in children, until they have attained their growth. Then, if the disease is not cured, we adopt radical measures. Conservative Treatment. — The main object of con- servative treatment is to deprive the joint of func- tion, and the measures that will most effectively deprive the joint of function are the measures we adopt. We are forced, however, to compromise. Complete deprivation of function means rest in bed with apparatus in addition, but the knowledge that we are dealing with a dangerous constitutional disorder makes us eager to get the patient up and about in order that his nutrition may be maintained at par. There are two general methods of carrying out conservative treatment: 1. Recumbency, with ap- propriate apparatus; 2. Ambulatory treatment, with apparatus. The first is an excellent routine treatment for the disease in its early stages, say for the first six months or a year, especially in children, for the acute painful exacerbations, and to meet special indications, such as large abscesses. It is not ordinarily practicable for adults for any length of time. Ambulatory treatment with apparatus is the usual means we adopt for most cases. In general the apparatus comes under two classes; plaster-of- Paris, and steel "braces." Some prefer one, some the other, but plaster seems to be making its way as the preferred form in this country. It is cheap, fits accurately, can be changed and thrown away, is obtainable everywhere, and cannot be removed by the patient without the surgeon's knowledge. It REFERENCE HAND HOOK OF THE MEDICAL SCIENC1 - Arthritis, Chronlo oeds some skill for its application, but so ;ll . s u brace. Braces are heller to meet .tain indications. They are much prefer- blein the presence of sinuses. \o patient , u l,l e i er be en( to a brace-maker with istructions to gel a brace. The surgeon peoify the kind of brace he wislies, ml must oversee the application. If un- to do this lie should use plaster, if knows what he wants, a. blacksmith and essmaker can carry out his instruc- ts. The task of measuring for a brace implified by taking a ca>t of the member ien by having the brace made over lis. \n brace nor plaster dressing should be upon to correct deformity. The de- Tinity should be corrected before the ap- aratus is applied. iith.r Methods of Conservative Treatment. treatment, passive hyperemia lungshyperaemie"), is based on the that venous stasis is hostile to the [opment of tuberculosis. Its method nation is by an Esmarch bandage above the joint just tightly enough . cause a reddening of the part, and a armth of it. It must not cause pain nor lake the part cold. The bandage is ap- lied for about two hours daily. This i;it meat is designed especially for the [bow. the wrist, and the ankle and tarsus. iMy is of use in some cases, but too inch should not be expected of it. It is .•r tor in open eases, i.e. those with sinuses, tian in closed ones. Klapp has devised a odification of the treatment by the use of i apparatus — glass chambers into liich the member is inserted, and from hich the air is exhausted. This is sometimes used ir tuberculosis of the bones of the hands, especially be lingers, and of the feet. Klapp also recom- Fio. 428. — Old Encapsulated Tubercle in Bone. It lay directly under urtilage. Its site could be told from the joint side by a dimple in the artilage. Note the fibrous capsule, and outside of this the strengthening f the bone trabecular. The dotted lines lead to two small islands of arulage. Although we possess no history of the resected adult knee rum which this specimen was taken, it is evidently a case of fighting up f an old process. Flo. 429. — Old Encapsulated Cheesy Tubercle, from Ankle-joint of a Boy about Eighteen Years Old. The joint had been treated conservatively for a number of years, and was supposed to be well. A resection was done because the joint had again become painful. The ankle was found full of fibrous ad- hesions, and in a recess of the joint this tubercle was discovered after a pro- longed search. The hospital laboratory had reported "chronic arthritis, no tuberculosis." mends his treatment by suction cups for tuberculous abscesses. Focal Operations. — These were designed with the idea of cutting down on an early tuberculous bone focus, and of removing it before it had in- volved the joint, but our study of the pathology will teach us why they are so rarely successful. The focus is almost never discrete, but ramifies in the marrow, and there is no known way of telling its full extent. Again, one of the favorite locations of the tuberculous granulations is di- rectly beneath the articular cartilage, and if we attempt to eradicate them, we immediately destroy the nutrition of the cartilage, and give the disease access to the joint. Tuberculin. Vaccines, etc. — Much has been ex- pected of this, but up to date the expectations have not been fulfilled. Possibly the future may make us reverse our opinion, but for the present tuberculin treatment should be pursued very cautiously at least. It seems to have little bene- ficial effect, if any. Treatment by Injections. — Certain observers have asserted that they could influence the course of a joint tuberculosis by the injection of various substances in and about the joint. Here again our knowledge of the morbid anatomy teaches us scepticism. No substance injected into the joint can influence in any way the disease in the bone, while blindly to inject fluids into the circumarticular structures, with the idea that they will pick out the diseased tissues and leave the healthy ones, seems irrational. There is no known specific against tuberculous granulations. Again, in many tuberculous joints there is prac- tically no joint cavity at all. The joint is a mass of fibrous adhesions, and what synovial mem- brane is left contains tubercles deep in its sub- stance. Formalin, carbolic acid, iodine, iodoform 679 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 432. — Tuberculous Knee, Anteroposterior View. Child about ten years old, treated conservatively for about three years. Discharged cured from Sea Breeze Hospital, with a fair amount of motion. Fig. 430. — Tuberculous Elbow after About Eighteen Months of Treatment by Plaster of Paris. Note disorganization of joint, erosion of cartilage, and areas of rarefaction and condensation of bone. Fig. 431.— Same Case as Fig. 430, Side View. Note the atrophy of the humerus. Patient about twenty-five years old. The pictures of this elbow may be said to be more or less typical of joint tuberculosis. Fig. 433. — Tuberculosis of the Knee, Lateral View of Joint shown in Fig. 432. 680 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis, Clirnnfr !'[,:. 434.— Tuberculous Knee in Adult. About ten years dura- Mi. Note disappearance of joint cartilage and the areas of and condensation of the bone. These were demon- rated at operation. Fatty osteomalacia was present to a larked degree. Fig. 436. — Bone Syphilis; duration four or five months. Pain, sensitiveness, etc., but no involvement of joint. Distinct history of paternal syphilis. This child had shown other symptoms of syphilis. Fig. 435. — Tuberculous Knee, Lateral View of Preceding Case. These skiagrams are more or less typical of a well advanced case of long standing. Fig. 437. — Sarcoma of Femur; Operated on for Tuberculosis. 681 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES have all had their vogue. Whatever use they possess is from their irritating properties. Possibly they Fig. 438. — Old Hemarthrosis of Knee. increase the production of fibrous tissue and so help to deprive the joint of function. Function may be abolished by much quicker means. Roentgen rays have their advocates, but as yet they have not proved their efficacy. The application of any substance whatever to the surface is without effect. This includes heat and cold. Massage and passive motion are distinctly contramdicated. Treatment said to iread along nder the an- trior liga- ■ •n t s and an. A ■ ■structionof lie vertebral ody often re- ti Its, and of he interver- cbral discs. "he support f the super- m p o s e d olumn is re- noved and it wings forward on the articular process as on a hinge, ansing a protrusion of the vertebral spines at the evel of the disease — the so-called "knuckle," or cyphosis, or humpback, almost diagnostic of Pott's ise. Sometimes one vertebra is affected, some- imes two or more. The bending of the spine causes til manner of deformities of the chest, and displaces he contents of the chest, and, to a lesser extent, of he abdomen. A peculiar facies often ensues. The runk is shortened as a whole. The arches of the iertebra are sometimes involved, with their articula- tors. The region most frequently attacked is the iumbothoraeie. According to the location of the dis- it is known as cervical, thoracic, or lumbar Pott's disease. The sacrum is seldom affected alone. Fig. 440. — Tuberculosis of the Seventh Cervical Vertebra. Abscesses are frequent. They usually form on the rior aspect of the -pine and make their wa surface by the lines of least resi d by gravity. Those of the upper cervical region appear in the back of the throat, and fficulty in ig. They may then appear on the aid the neck, or in the ! A. Schmidt). Abscesses of the lower cervical region pass into the posterior mediastinum, follow the aorta downward, and may appear in the thigh. Al tho- racic spine rarely penetrate the pleura, but usually sink by the side Of the aorta, and reach the pelvis. Later they pass under Poupart's ligament into the thigh, or occasionally through the great sciatic fora- into the glu;> Abscesses of the lumbar region follow the course of the iliopsoas muscle under Poupart's lig- ament. All sorts of devi- ations from these courses are met. Sometimes the ab disappears without reaching the surface. In disease of the vertebral arches the ab- scess usually appears in the back. The spinal cord may be damaged by the pressure of the prod- ucts of in- flammation in the vertebral bodies, but rarely if ever by the pinch- ing of the cord by the angu- lar deformity. The lumen of the canal is not dimin- ished. A kyphosis once formed is permanent. It may be re- duced some- what by persistent treatment, but cannot be made permanently to disappear. Symptomatology. — Spasm of the back muscles is early and prominent. The attitude of the patient is often changed, and the normal contour of the spine disappears. Sometimes the kyphosis appears early, sometimes late. The patient stoops awkwardly, and sits and stands stiffly. Sensitiveness to pressure is not ordinarily present, for the diseased portion of the spine is deeply located. The pain is occasionally felt in the back, but more often, on account of the involvement of the spinal nerves, shoots down the arms, around the trunk or down the lower extrem- ities, according to the location of the disease. The knee-jerks are often exaggerated, the gait spastic. 683 Ahrtritls, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 441. — The Whitman-Bradford Frame. Paralysis of the lower extremities (Pott's paraplegia) is fairly frequent, and the functions of the bladder and rectum may be compromised, causing incontin- ence or retention of the feces and of urine. Respi- ration may also be ab- normal; grunting respi- ration or a peculiar "futile" cough may be present. The spine may show a lateral curvature. Diagnosis. — In rotary lateral curvature the apex of the curve is on the ribs, not on the spine itself. Pain is absent or practically so, spasm also. There is no true kyphosis in this disease. Spinal fractures are often followed by a kyphosis, but the symptoms follow immediately on severe injury. Certain injuries of the spine without demonstrable fracture are also followed by a slowly developing kyphosis, and may sim- ulate Pott's disease, but the signs of active dis- ease are absent. T;/- phoid spine follows ty- phoid fever, is wont to be very acute and pain- ful, and very rarely is Fig. 442. — Ordinary or Old-fashio jacket on the left fails to accompanied by a kyphosis. The psoas abscesses of Pott's disease may be mistaken for appendicitis but they are less acute in their course, and have not the 684 symptoms of an inflammatory lesion. Chronic non-tuberculous arthritis is wont to involve a large segment of the spine, and other joints of the body. Masses of new bone may often be detected in the skiagram. Rickets, new growths, hip disease and nem must also be carefully excluded. "Lumbagi and "sciatica" are often caused by Pott's disease. Progn osis. — T his is somewhat more grave than in tuberculosis of other joints, especially in adults. The length of time necessary for a cure by conservative means ranges from two to about ten years. Disease of the cervical region runs a somewhat shorter course than that of the thoracic and lum- bar regions, but has an added danger in the proximity of vital struc- tures. Relapses are fre- quent. Often the ap- pearance of an ali- long after the apparent cure, shows the activity of the process. Radical Treatment. — Until very recently all fruitless, but the work of ned Jackets. Observe how the control the deformity. radical treatment was Hibbs 7 and Albee 8 in the line of producing complete bony ankylosis promises a future for it. Albee splits REFERENCE HANDBOOK OF THE MEDICAL Si II NCES Arthritis, Chronic ie spinous processes and grafts into them a piece bone removed from the patient's tibia. The Deration is based on sound pathological principles, n,l should be a success in adults, for ii destroys mo- on i" 1 1"' spine, and hence must cut off the pabulum ir the disease. rvative Treatment. — The best routine treat- the firsl six months or a year is by recuro Flo. 443. — Application of the Calot Jacket wiih Officer's "Collar"; trimming the jacket. bency in a jacket or on some rigid form of apparatus, ■ 7. the Whit man- Bradford frame or a plaster-of- I 'aris bed. The Whit man- Bradford frame is composed of an oblong frame of gas-pipe with elbows at the corners. Over this is stretched a canvas cover I up the back. The frame is bent backward at the seat of the disease, and the patient is strapped to it by means of an "apron'' over his chest. He is rpermitted to sit or to stand for an instant from I lie time the treatment is begun until it is finished. The frame is also suitable for cases with large abscesses, or for those complicated by paraplegia, and for all cases when the pain cannot be checked by other means. It finds its greatest usefulness among children. Ambulatory treatment is useful during most of the di ease. Ii ran be carried ouf by plaster jackets or bv brace Plaster jackets arc of two kind-, thai devised by Sayre the ordinary jacket and thai by Calol \ jacket to be of use must extend well beyond the -eat of disease in both directions in order to obtain proper leverage, it must l»- padded over i in- bony prom- inences, must be strong enough to stand the -train, but must not be '> thick a to be unwieldy. It should be applied over a seamless shirt. It may be put on while (he patient is strung up, or while i,, i prone or supine. The first is the usual method. Ordinary plaster jackets may be supplied with a ''jun ma i ' tu support the head in disease of the cervical region, but this is not a very efficacious met ho, I ol I real i ne 1,1 A " window" may be cut in I lie plaster over t he abdomen to provide for the increa e in size after eating. A strip of linen under the shirt- ing in front and back adds to the comfort of the patient by giving his skin a rub under the plaster, aided by dusting powder. An excoriation imme- Fig. 444. — Grand Calot Jacket. Anterior View. This was a case of subluxation of the atlas, wrongly diagnosed at first as cervical Pott's disease. diately makes its presence known by a foul odor, (are should be taken not to permit any foreign body to slip down inside the jacket. The Calot jacket (see illustration) is an excellent means of treatment for disease of the upper thoracic and of the cervical vertebra?. It needs considerable practice for its proper application. Braces. — These are the original brace devised by Fayette Taylor, and the various modifications of it. The brace consists of a pelvic band, and of two upright steel bars springing from it. one on either side of the spinous processes. The brace is held to the body by its attachment to an apron in front and by shoulder straps. In cervical disease it is 685 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES provided with various kinds of head pieces and chin pieces. Tuberculous Hip-joixt Disease. — (Coxitis, Mor- bus coxarius). Pathology . — The primary focus may be in the head, or probably in the inner portion of the ueck, in the acetabulum, or in the synovial Fig. 445. — Early Hip Disease of Right Leg, Showing Abduction. membrane The head may be almost entirely eaten away, but rarely sufficiently to cause a luxation. The acetabulum may be perforated, giving the prod- ucts of disease access to the pelvis. The spasm of the muscles in a set attitude (adduction and flexion) crowds the femoral head against the upper portion of the acetabulum, and often by pressure wears it more or less away, so that the upper borderis pushed upward and a subluxation takes place — "wandering acetabulum". Symptomatology. — Pain and limp are early and prominent symptoms. The pain may be felt in the hip or in the knee. In the latter case the disease in the hip is often entirely overlooked. At first the thigh may be in an attitude of extension and abduc- tion, but this soon gives place to the characteristic attitude of flexion, adduction, and internal rotation. Sensitiveness of the head of the bone to pressure may or may not be present. Abscesses when present usually break through the joint at its weaker lower portion and appear on the front of the thigh. Diagnosis. — In lower Pott's disease, the thigh may be held in semiflexion, but limitation of motion as a rule is manifest only in the direction of extension. In some cases the diagnosis can be made only after several examinations. In non-tuberculous arthritis of Type II, muscular spasm is absent, the obstruction 686 to motion is purely mechanical, the Roentgen ra\ show the production of new bone, and as a rule th thigh is in abduction. Sprains in childhood cles up after the hip has been put in plaster for a few week Fracture of the neck, and epiphyseal separation ar differentiated by the history and by the use of th x-rays. In coxa vara the thigh is in extensioi adduction and external rotation, and the skiagrai shows the bend in the femoral neck. CongeniV Fig. 446. — Severe Hip Disease, with Adduction. dislocation gives a history of existence since the time the child began to walk, absence of pain or signs of inflammation, and free motion in all directions except abduction. Examination and the Roentgen rays reveal the femoral head out of the acetabulum. Conservative Treatment. — The first indication is a reduction of the deformity. The desired position is one of extension and slight abduction. Then one may use any of several kinds of apparatus. A good routine treatment is by the short plaster-of- Paris spica with or without crutches and a high shoe on the sound limb. The traction brace in one of it? numerous forms has enthusiastic advocates. The Thomas brace is sometimes used, but is difficult to fit, and seems to possess few advantages over the spica. In Germany the long plaster dressing is much used. Treatment in an ordinary case should be continued for about three years. Toward the end the brace ia left off at night, "then one or two hours a day, and the joint is carefully watched for symptoms of a return of the disease. If spasm and pain reappear, the ap- paratus should be reapplied. Radical Treatment. — It is quite manifest that no operation has been devised that could certainly REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis, Chronic Fig. 417. — Traction in Hip Disease remove nil infected tissue, fur the ot innomina offers do field fur extensive a. The re after hip-joint resections has been said to be bad, I'm tin- i- perhaps because drainage has been used and the joint has been secondarily infected. Our sole object must be to d< troy the joint. This may be done in either one of two ways. 1. The head of the femur may he removed, causing a dislocation. In this ca>e the joint as such ces to exist, and the stump of the femoral neck is slung by the liga- ments upon the ilii. Vari- ous routes of access to the joint have been proposed. Possibly the simplest is through the anterior incision downward from the ante- rior spine, going outside the Nr-J Ha. 448.— Hip Splint in Use at the Children's Hospital. Boston. (Courtesy of Dr. Bradford.) lorius in order to avoid the branches of the crural nerve. Drainage is not necessary. A plaster spica should be worn for two or three months afterward. The func- tional result is usually good. The shortening amounts to about two and one-half inches, and the patient walks fairly well with the aid of a high shoe and a cane. Albee, of New York, has proposed an ankylosing operation which appears to be quite efficacious (see page 697). The ankylosis resulting from it should give a better result for walking than the dislocation, but not so good for sitting. Tuberculosis op the K.vee. — (White swelling, etc.). Pathology. — The primary focus may be in any one of the three bones, or in the synovia. The most frequent bony site is in the head of the tibia. The proliferation of the synovia is sometimes more marked in this joint fi G . 449.. than in any other and causes great swelling, giv- ing the disease its common names of "joint fungus" or "white swelling." On the other hand, the synovia may be fibrous and contracted, causing the bone ends to stand out and to look enlarged. The enlargement is only apparent. Symptoms and Physical Signs. — Atrophy, both of the thigh and calf, especially in the bony type, is early and marked. The knee is held in semiflexion. In this attitude the flexors work at an advantage over the extensors, and often pull the head of the tibia backward, subluxating it on the femoral con- dyles. At the same time the leg is rotated some- what outward. The ligaments adapt themselves to this position, so that even if the hamstrings be divided and manual force be exerted to extend the leg, the normal attitude is not attained, but the -Long Traction Splint Applied. 687 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fir,. 450.— Thomas' Hip Splint, Single. (Itidlon.) head of the tibia is levered backward, and the bone adopts a position in a plane posterior to that of the femur. Sensitiveness of the synovia can often be detected if the joint be semiflexed. Fluid may be present or it may not. The patella may float. A boggy feel of the soft parts is charac- teristic of the cases with great synovial proliferation. Diagnosis.- — The special diffi- culty presented in this joint is the differentiation between tuberculosis and the non-tuber- culous forms of Type I. Fre- quently one can decide only after months of observation, unless the animal test be used. Conservative Treatment.- — If one elects the traction treat- ment, one applies the Thomas knee brace, made two or three inches longer than the limb, to swing the foot clear of the ground, and provides the other foot with a high shoe to com- pensate. If one elects immob- ilization, one encases the limb in a plaster-of-Paris dressing reaching from the perineum to the malleoli. In the late stages of the disease the Campbell brace is useful, jointed at the knee to allow the desired amount of motion. Radical Treatment. — The sole object of this is to stiffen the knee. An excellent means of do- ing this is to saw through the patella, to dissect this out, and then to remove by the chisel and saw a small slice from the tibia and from the femoral con- dyles. No time should be wasted in dissecting out the synovia. If the semilunar fibrocartil- ages be removed the subsequent pain will probably be less. The wound should be sewn up without drainage, and the limb should be put up in full extension in plaster-of-Paris. 9 Ankle and Tarsus. — Pathology. — The dis- ease is complicated in this situation by the presence of a number of small spongy bones and of six or seven synovial cavities. A focus in one bone may soon involve two or three synoviae, and the disease may run riot through the other bones and synovial membranes. The pri- mary focus is most often located in the talus. Abscess forma- tion in these joints is early and frequent. A peculiar form of the disease, found most oftei in children, is located in the anterior portion of th> calcaneus, ruptures externally, and shows litt], tendency to involve the joint. Sequestra are oftei formed in disease of the calcaneus. Symptomatology. — The foot may be in any one of : number of different attitudes. In disease of thi ankle, the patient often walks on his toes — equinus In disease of the midtarsus the attitude is frequent!' calcaneovalgus. Fig. 451.— The Lorenz Short Spica. A Sea Breeze Case. 1 Fig. 452. — The Lorenz Short Spica. Note the calf develop- ment on the affected side, and the excellent condition of the children. Diagnosis. — Painful flat-foot with rigidity may simulate tuberculosis, but it lacks all signs of acin< inflammation. A peculiar puffiness under the exter- nal malleolus seen often in normal women is not to be mistaken for disease. Conservative treatment is carried out by a plaster- of-Paris dressing reaching from the level of the head of the fibula to the toes. Inasmuch as the impfti I of this dressing with the ground would soon destroy it, the foot must be swung clear by the use of a Thomas knee brace. The other foot must be pro- vided with a high shoe. The treatment by Bier's hyperemia is supposed to be especially adapted for use in this region. Conservative treatment is usually very efficacious in children. Radical Treatment. — If the disease be diagnosed early enough, while still located in one bone, befi synovial involvement, it may possibly be cured bj the simple removal of that bone. Otherwise the most extensive resection will be necessary, removing every particle of infected tissue. This will often be css REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthritis, ( hroiilr possible, and we shall be obliged to amputate, tie-joint alone be involved, the disease may en be cured by ablation of the talus and dostruc- the joint. The operation of curetting for berculosis of the ankle and tarsus can be based only an ignorance of the underlying morbid process. Iiif Wrist. — The pathology and principles of :atment in disease of this joint are much the same those already laid down for the ankle. must be differentiated from Duplay's bursitis — sub- deltoid or subacromial bursitis. In this the limitation of motion is always in the direction of abduction and externa] rotation. The skiagram is most important, in t he different iation. Conservative treatment consists in bandaging the arm to the chest, or in the use of apparatus to restrict its motion. The value of the popular shoulder-cap is illusory. Radical treatment consists of subperiosteal re tion, which gives anankylo- sis, a fairly useful result on account of the mobility of [in- capula. -t i 158. — From Left to Right: Schultze Pelvic Rest, Authors' Modi6eation of the Lorenz Plevic Rest, Loreuz Stirrup, Head and Shoulder Rest. The Elbow. — Disease of the elbow possesses cer- in peculiarities. There are two joints here, one of Inch may be affected alone or both together. The ses with bony focus are said to begin most fre- in the ulna. The attitude of the elbow is ually semiflexion. If the radio-ulnar joint be impli- i the forearm is in semipronation. i motive treatment is carried out with the elbow Id by a plaster bandage at a right angle. A sling - the patient to bear the limb with comfort. the case comes under observation it h the elbow at a greater angle of -ion, it should be flexed under sthetic, or better still, it should i slung from the wrist about the ick with the patient's head well xed. As he slowly straightens his ick up he will flex the elbow. This rocedure is repeated each day until le required amount of flexion is 'tired. Radical Treatment. — Either one of vo conditions results from a resec- on, a rather loose, movable, and lirly useful relation of the two bones h other (it is probably not an ticulation in the usual acceptation :" the word), or a bony ankylosis. he latter is said to result if the joint e put up for a week or two in exten- di and then be flexed. Resection "ild always be done subperiosteally, and care lould be taken to avoid injury- of the ulnar nerve, "ine operators insist on the use of apparatus for while after the plaster is removed. The Shoulder. — This is the joint in which the »rm of the disease known as caries sicca most ften occurs. The head of the humerus in this is aten away, without the formation of abscess. It The Sacroiliac Joint. — Tuberculosis is a very serious disease in this joint, but a very rare one. The pain is Located at the seat of disea e or runs into tin- buttock or down the thigh. A marked limp is present, and the trunk is inclined toward the sound side. Abscesses are a fre- quent complication, are prone to early infection, and bur- row in every direction. Sometimes they rupture into the pelvis, sometimes exter- nally. Fluctuation may be detected by inspection, or by the finger in the rectum; sensitiveness also. The prog- nosis is bad. The conserva- tive treatment is best car- ried out by a plaster spica, crutches, and by a high shoe on the opposite extremity. Radical treatment might meet with better success than it has in the past if it were undertaken early and strove only for ankylosis. The Fingers and Toes. — This is known also as tuberculous dactylitis and spina ventosa. In adults the joints themselves are usually diseased, in children the shafts of the bones. To the latter the term spina ventosa should be limited. The disease often affects two or more fingers. Abscess is usual. Fig. 454. — Subluxation in Tumor Albus. Spina ventosa must be differentiated from syphilitic dactylitis — not always an easy task. The problem is sometimes solved with the aid of the Wassermann and the tuberculin tests, by the examination of a piece of the wall of an existing sinus, or by a course of antisyphilitic treatment. In disease of the meta- tarsophalangeal joint in the adult gout must be excluded by the .r-rays and by the course of the disease. Vol. I.— 44 689 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The treatment in children consists largely of clean- liness, and sometimes of suction by hyperemia. It is usually efficacious if persisted in. Radical Operations. — Extirpation of the diseased bone, and bone grafting have been practised with success." In tuberculosis of the finger-joints of adults the question arises as to the advisability of resection or \ » k Fig. 455. — The Tin Knee Splint. Report.) (Children's Hospital of amputation, and this question must be decided according to the importance of the member and the severity of the disease. If secondary infection have already taken place an amputation is probably preferable. NON-TUBEHCTJL.OTJS ARTHRITIS OP TYPE I. All the other forms of disease included in this type shade into one another without sharp dividing line, and to various of them special names are given; thus, Still's disease is a form occurring in young children, but a similar disease exists in adults. A synovitis may occur as a tertiary manifestation of syphilis, but if the marrow in the bone ends be involved then the disease comes under the head of chronic arthritis. It will be best therefore to take up first the main group, and later to describe the special forms, and in order to avoid confusion we shall simply consider this main group under the name of chronic non- tuberculous arthritis of Type I. Pathology. — The morbid anatomy is much the same as that of joint tuberculosis, lacking only the characteristic tubercle, the areas of necrosis, and the formation of cold abscesses. Hale White" shows a photomicrograph of a section of a joint obtained at autopsy which needs only the presence of tubercles to be characteristic of tuberculosis. The main features of this type are a proliferation of the synovia and of the lymphoid marrow. Some- times one occurs alone, sometimes both occur together. 690 In the latter case, some writers say that one is t earlier manifestation, some say the other. We i justified in believing, then, that both may be right' the cases they have examined, and that either t synovia or the marrow may be first affected. This proliferation in the synovia and in the mam is the essential factor of the disease, and all bony a cartilaginous changes are to be reckoned as due to The synovia is thickened and inflamed. It thrown into folds and shows marked villous hyp< trophy. Parenthetically it may be said that tin is do such clinical entity as "villous arthritis." T formation of synovial "tags" is rather frequei Under the microscope the ordinary signs of chroi inflammation may be seen, namely", thickened blon vessels, round-cell infiltration, etc. The synovia stead of consisting of a single layer of cells, posed of a layer of lymphoid tissue. It reminds o of moss on a rock. Not only is the synovia thickened and in fok but it extends its border at the expense of the arti ular cartilage. The .Marrow. — Various changes have been d scribed by different writers. Hale White" fout foci of recent inflammation. Nichols ami Richai son 12 regard a proliferation of the connective tissi as the chief change. Nathan 13 describes a cyst l mation and the formation of dense conneeti\< in spots like "foci." The proliferating marrow impairing the nutritif of the overlying cartilage bursts through it and ii vades the joint. Here it meets the proliferatii synovia and the proliferating marrow from tl other bone of the articulation, and forms adhesio* with them. Sometimes the joint is but a mass adhesions. This proliferating cellular tissue lati may change to fibrous tissue. Fig. 456. — Tuberculous Disease of the Ankle; Advanced Stage. Most writers affirm that the synovia is the first tissue to show proliferation, but Nathan assert- that the marrow changes precede those in the synovia. The Bone. — The essential feature of the bone change in this type is an atrophy. Although, accord- ing to Nichols and Richardson, in the early stages no evidence of this atrophy can be seen under the microscope, nevertheless the bone is distinctly more permeable to the Roentgen rays. Usually the re- sult of the morbid process is seen in thinning of the bone trabecules. REFERENCE BANDBOOK OF THE MEDICAL SCIENCES Arthritis, Chronic ||„. Curtilage. -The cartilage is aiVeeled in a man , perhaps mere striking than any other of the sues. It becomes thinned, atrophic, ami. de- • * \ I i.:. 457. — Tuberculosis of the Tarsus. Talo-navicular joint lai'l Note erosion of articular cartilage. rived of its nutrition by the proliferating marrow, rates, and is perforated by the granulations in marrow. It is probably never lifted md .hrown off in a leaf, as in tubercu- isia. At the same time it is assaulted, so ik. by the synovia, and suffers a ■ linking of its borders. As a result of a motion or of a disturbance in nutri- .11 or of both, the cartilage undergoes a illation, and as the result, again, of the tree processes just detailed, it may disap- e:ir more or less completely. Sometimes mall islands or strips of cartilage are seen •abedded in granulation tissue. \s the cartilage disappears a fibrous nkylosis is formed in the joint. Accord- ig to some writers, an occasional complete r bony ankylosis takes place. The ligaments are said to be thickened. Symptomatology and Course. — It is neces- ary to keep in mind the difference be- a joint that has been the seat of an disease, and in which, after the sub- idenceof the disease, stiffness and loss of unction remain, and a joint which is the eat of an actual chronic disease or of a isease which manifests itself by a series ■f acute exacerbations. It is only the lat- er type of joint disease with which we have o deal here. The onset of the type under discussion nay be sudden, with high fever and con- titutional disturbance, or it may be slow nd insidious. One joint may be affected lone, or many joints may be involved, it her at the same time, or one after another n quick succession, or at long intervals. \fter a joint has been invaded the symp- oma and physical signs in it do not clear ip completely when other joints are in- olved, as they do in acute inflammatory heumatism, but the joint is permanently lamaged by the structural changes in it. In what may be termed the classical onn of this type, the tendency to involve- nent of many joints is marked, the char- icter is wont to be symmetrical, and in a leneral way the disease manifests a " cen- ripetal" nature, that is, the joints of the hands and feel suffer fir t, then the knees ami elbows. The proximal interphalangeal joints and the meta- carpophalangeal, are often affected. The hips often escape, bul the pine i \ ulnerable. In anol her the spine and hip seal "i disease— ■■ on I iechtei ■ i j pe. \ arious write] - ha\ e at- tempted to build up clinical etiti- i- of locality of the joint inflammation — such as von Bechteiv npell- Mai ie' di ea e, etc.— bul t heir claims have not received general recognii ion. The anemia which so often ac- com] tanii evi re fi inns of the dis- ease is hard to explain. 1 1 may be said i e i arac- teristic bl 1 changes. Si >me ob- ser\ ers ha-, e found a decrea red blood cells, but as a ruli number is about normal Leuco- i'\ ti -is may or may not be pi i Except possibly in its mild forms this type is wont to be multiarticular. Sometimes the onset is pre- ceded by various local nervous dist urbances — tingling, numbness, stiffness, weakness, hyperesthesia, and circulatory muscular cramps, Fig. 45S. — Tuberculosis of the Calcaneus. 691 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES change in color, etc. In other cases the onset is unheralded. The affected limbs may be atrophic or they may be the seat of a sort of pseudoedema. The skin and nails often show trophic disturbances. Extreme sweating may be present, and various paresthesias. Pigmentation of the skin is occasionally seen. The occasional coexistence of Raynaud's disease, exoph- r Fig. 459. — Tuberculosis of the Carpus. thalmic goiter, nephritis, paralysis agitans, and arterial sclerosis has been observed. 11 The general condition of the patient varies. He may be able to go about with more or less comfort, especially in the intervals of the paroxysms, or he may be completely bedridden, and unable to move hand or foot. Often with the steady progression of the disease, the patient becomes gradually more helpless. Contractures are often present in the affected limbs, and the reflexes are wont to be exag- gerated. Local Symptoms and Physical Signs. — Pain is almost invariably present, and ranges from mild to very severe. The slightest motion may occasion great agony. Stiff- ness and loss of function accom- pany the pain. The joints are swollen, and often reddened. In the later stages of the disease the swelling may give place to a shrinking and atrophy, which gives a certain constriction at the level of the joint. The charac- teristic swelling is "boggy," caused less by the effusion in the joint than by a thickening of the synovia. Where the synovia is accessible to the examining finger, sensitiveness can be elicited. The usual deformity is flexion. Motion in the affected joint is limited, not only by the pain, but also by the products of inflam- mation. Creaking and grating can often be detected. The severe "classical" form of the disease is really not the common one, but represents the morbid process carried to an extreme. In the majority of cases of this type the patient experiences more or less pain, stiffness, and disability in one or two joints. The skiagram of the joint reveals what one would expect after a study of the pathology. If the in- flammation is confined to the synovia, this will be seen thickened and swollen. If the bone is affected, it will show in the picture as rarefied, and the car- tilage as thinned and eroded. Bony hypertrophies and exostoses do not belong in this type. Differential Diagnosis. — At the start the differ- entiation may be impossible between acute inflam. matory rheumatism and the chronic forms of arthritis which begin acutely, but the subsequent course will always suffice. A higher tempera- ture is the rule with rheumatism, and its acid sweats are probably peculiar to it. Heart complications are rare with chronic arthritis. Above all, rheumatism flits from joint to joint involving one at a time, and leaving no trace behind. A gonorrheal joint inflammation i.> wont to run a distinctly acute course, and, when it subsides, to leave the joint damaged, but not the seat of a progressive, active disease. On the other hand, it is probably a fact that a gonorrheal joint may closely simu- late the disease under discussion, and possibly may be pathologically so allied to it as really to belong in the same class. The condition of the genito-urinary apparatus may enable us to place the gonorrheal joint in its proper class, or perhaps the cultivation of the gonococcus from some aspirated joint fluid. We have seen that the pathological process i: tuberculosis is almost identical with that in the ordi- nary proliferating type of arthritis. It follows, then, that the symptoms and physical signs are the same, or so nearly the same as often to prevent a diagnosis from them alone. The skiagram is also the same. The main points which distinguish tuberculosis clin- ically are its slow and steadily progressive course, its almost invariable uniarticular nature and its tendency [ Fig. 460. — Tuberculosis of the Carpus. to produce abscess. The tuberculin reactions are not of conclusive value in adults, but the animal test or a laboratory examination of a piece of the synovia are of much more importance. The chief difficulty in diagnosing this type o( chronic arthritis will be found in the very mild ■ in which the synovia alone of one joint is involved, and which occasion practically no symptoms exi moderate pain of more or less constancy, and it is G9L' REFERENCE HANDBOOK OF THE MEDICAL SCIENI ES Artlirltl-. Chronic these cases that the painstaking complete Mica] examination is most important. In ,'. m . often the detection of the source of the 'ection and its removal, not only cures the disease, but clears up the diagnosis. Tin- prognosis is fairly good if one can find out e of the disease. If it cannot be cured may at least be checked, and t lie patient may restored to a fair degree of health. The |ut more or less general, and produces cartilaginous outgrowths and spurs, which may later undergo transformation into bone, The bone under nca ih the articular cartilage hypertrophies at t ho --a mo time. Now , i he cartilage draws its nutri- tion from the marrow, and when this nutrition has I n loit oil' i.\ i he \ bone, t he carl ilage degener- ate . and wears away, often leaving the bone exposed and ebumated, grooved in the line of joint motion. The peripheral portions of the cartilage, drawing their nutrition probably from (he synovia do out suffer in this manner, bul maintain their hvpertrophiod condition, and give (o the bone end an enlarged and flattened contour, adding to the distortion, .-11111 sometime causing subluxations. Between the ebur- nated bone ends there is no tendency to ankylo is as in Type I, and there is no proliferating marrow to break through the cartilage. Whatever obstruc- tion to motion is present, is purely mechanical. Symptomatology. — As a rule the onset of the dis- ease is insidious, with moderate pain and stiffness, and the course is more or less progressive, until the process is finished, when the joint is left more or le 3 damaged functionally. The pain is rarely great, and lesions of this type are not so severe in their effects as are those of Type I. The joints as a rule are not much swollen, but the bone ends show irregular en- largements. Subluxations are frequent, on account of the change in shape of the articulating surfaces. Sensitiveness to pressure is rarely present. In the hip the usual deformity is flexion, abduction and external rotation; in the knee, flexion; in the fingers, lateral distortion. Creaking and grating can be dis- tinguished on palpation, and motion is limited. The atrophy of disuse may be detected with the tape. Disturbed digestion is often present, but no fever nor other constitutional disturbances. Roentgen rays show the bony and cartilaginous growths, the thickening of the cartilage and of the bone near the joint, and the wearing away of the cartilage near the center, in the line of joint motion. Diagnosis. — Cases in Type I. are wont to be ac- companied by more constitutional disturbance, are more painful, and show more acute manifestations. A skiagram shows a rarefaction of the bone, no bony nor cartilaginous growths, and a thinning of the car- tilage. Inflammation is more marked in cases of Type I, and bony and cartilaginous growths do not occur in it. Tuberculosis may be hard to differentiate from the Fiu. 166.- -Dactylitis in Boy of about Nine Years. He had a distinct history of a syphilitic parent, but the lesions did not heal up under anti-syphilitic treatment. 695 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES uniarticular forms, but tuberculosis also shows more signs of active disease and inflammation, more mus- cular spasm, and greater pain and sensitiveness as a rule. The tuberculin reaction may be present. One misses in tuberculosis also the cartilaginous and bony spurs. The obstruction to motion in tuber- Fig. 467. — Photomicrograph, Low Power, Showing Bizarre Appearance of Cartilage, from Knee with Mixed Infection. culosis is caused by inflammatory products and by muscular spasm; in cases of Type II, by mechanical impediment. The Roentgen rays are the most useful means of diagnosis. Sometimes the differentiation can be made only by several examinations at intervals of time. Fig. 46S.- -Low Power Photomicrograph Showing Fibrous Change in the .Marrow. The prognosis quoad vitam, unless the spine is involved, is good; as to function it is bad. The dam- age once done to a joint is permanent, and a return to perfect function usually impossible. Treatment. — Here, as in other forms, one endeavors to find a source of infection, and to remove it. If this be possible, one may arrest the march of tt morbid process. Intestinal fermentation is to t corrected, and also enteroptosis. Passive motion an massage are contraindicated. They harm the joir by the trauma they inflict through the medium i the rough bony surfaces. Sometimes a well-fittii Fig. 469. — Photomicrograph of Marrow Cyst from Hip Joint. brace, which allows motion through a painless arc may enable the patient to use the affected joint witl a reasonable degree of comfort. If one or two bom spurs be identified as causing most of the restrictioi. they may be chiseled away, in the uniarticular form: especially. In the case of a badly damaged singk Fig. 470. — Low Power Photomicrograph Showing Degeneration of Cartilage in Type II — the so-called Cartilage "Tatters." joint a stiffening operation may be thought advisable, for a perfectly stiff, painless joint is far preferable to a painful one with a small range of motion. In the knee this may easily be done by the removal of the articular cartilages, with a small slice of bone. In the hip Albee's operation is perhaps the best resort.'" 696 REFERENCE HANDBOOK OF THE Ml I'M \I. SCIENCES Arthrllls, < hniiilr yibee removes the upper part of the head of the cmur the upper portion of the acetabulum, and as nuch'as possible of the cartilage from the head of he femur, subluxates the femur upward, and puts lie thigh up '" slight abduction and flexion until >ony union takes place. With the destruction of he joint, the disease disappears. Fig. 471. — Same as tig. 470; High Power. Special Forms. — Hebcrden's nodes are small bony growths usually occurring at the terminal inter- phalangeal joints of the fingers, and have been said to be an evidence of longevity. They occasion slight discomfort, and slight interference with func- tion. The deformity resulting is usually lateral, in Fig. 472. — Lower Power Photomicrograph Showing Irregularity of Joint Cartilage. contradistinction to the flexions caused by lesions of Type I. The latter form affects more often' the proximal interphalangeal joints or the metacarpo- phalangeal. Treatment of Herberden's nodes is not often necessary. Spinal Form. — The lesions in the spine are wont to be severe, not only from the extent of the damage, and its crippling effect, l>ut also on account of the effect upon the vital means through the interference with their function. A part of the spine maj be involved or the whole column. Of ten the two upper- most joints escape. The joints become ankyli I more or less c pletely. Sometimes masses of bone form on the anterior aspect ot the -pine, turnii into a bony ma I'lie intervertebral discs may be lied, or the joints may persist, though surround- ed by masses of bone. If they persist the spine may lose its normal curve and be converted into a more or less straight rod — "poker pine." If they be absorbed tie- spine may possess one long, rounded posterior curve. The symptoms are pain, disability, stiffness, and weakness. The pain is caused by pressure on the spinal nerves, and is felt not only in the back, but Fig. 473. — Charcot's Disease. (Weigel.) also down the limbs and about the trunk. The knee- jerks are often increased. The disability may be extreme, especially if a complicating lesion of other joints be present. Probably the best form of special treatment is by the use of a brace, or better still, of a plaster jacket, to prevent the increase of the deformity if not the spread of the disease. It is seen that if the ante- rior bowing of the spine be prevented, while the inter- vertebral discs are being absorbed, but before bony union has taken place, the subsequent condition of the patient will be bettered. Of any attempt to break up bony union here there should, of course, be no thought. Charcot's Joint, Trophic or Neuropathic Joint. — This form of joint disease probably belongs in this tvpe. though it possesses features of both types. It sometimes complicates a tabes or a syringomyelia. G97 Arthritis, Chronic REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The knee is most frequently affected, then the hip, then the ankle, then the spine. The joint becomes badly disorganized, and often contains loose pieces of bone and cartilage. Pain is absent, but the swelling and loss of function are marked. The joint becomes very lax, and motion is possible in abnormal direc- tions. The conservative opinion seems to be that operative measures are useless in this affection. A jointed brace affording limited motion gives the best prospect of relief. Poncet's tuberculous rheumatism is a form of joint disease which Poneet has considered to be due to a sort of attenuated virus acting upon the tissues of the joint. He thinks that a large proportion of cases of chronic rheumatism are due to this cause, but as yet his observations are viewed with some degree of scepticism. It is possible that the fleeting joint symptoms often observed in tuberculous patients are due to a secondary infection. Bier Treatment (Stauungshyperaemie). — In various forms of chronic arthritis, tuberculous and other, a Ankylosis. — After any chronic joint disease has run its course, or indeed, after any acute one, a certain amount of stiffness is wont to be left behind and to this stiffness the name ankylosis lias been applied. It is necessary to have a thorough com- prehension of this subject if one would undertake the after treatment of these joints, and to know the exact pathological condition in them. Otherwise one risks disaster in attempting to mobilize them. Two kinds of ankylosis are recognized, namely, true or complete or bony, and false or incomplete or fibrous. Fibrous ankylosis may be so firm as to simu- late the bony variety, and may possibly be differen- tiated only by an examination under ether, or by a Roentgen picture. First, let it be said that immobilization probably never causes ankylosis by itself. If a normal joint be immobilized for a length of time, the synovia encroaches upon the joint cartilage and the latter becomes fibrillated. Some stiffness will be present when the dressing is removed, but this stiffness will disappear upon the resumption of function, and Fig. 474. — Patient in Bed on Fixation Frame, with Traction in Line of Deformity. treatment, named after its originator, has been advocated, which consists of the production of a venous stasis in the limb, to be continued for one hour to three hours daily. The stasis is brought about by the application of an elastic band above the joint, which should be applied just tightly enough to make the portion of the limb distal to it bluish-red and warm but not -painful. Klapp, Bier's assistant, devised a modification of the treatment for use in tuberculous joints with open sinuses or open absces- ses. He used specially devised cupping glasses. To i*duce a suction hyperemia in a limb he inserts it in a glass chamber, whose open extremity is provided with an open cuff for bandaging on the limb. The air is then exhausted from the air chamber. The Bier treatment at one time had a wide vogue, but seems to be falling into disrepute. It certainly merits a trial in some cases, but too much should not be expected of it. The amelioration of the symptoms of pain and sensitiveness, which often takes place, may lie due to a reduction of the disease process, or possibly may be due to simple pressure on the nerves. some observers have said that the obstruction to motion in this case is located in the tendons, and disappears when they are divided. This fact should be kept firmly in mind. The principles governing the treatment of ankylosis vary according to conditions, and according to the disease which has caused it, but no mobilizing opera- tion should ever be undertaken in a tuberculous joint while the disease is in its active stage or when it has run its course, and is apparently well. When the disease is active it will be aggravated by motion, and one can never tell when it is well." An old, appar- ently healed joint usually contains encapsulated foci of tuberculous material, which occasion no disturbance until trauma or ill-advised operations set them free, and light up the trouble afresh. If, in the active stages, one undertakes the treatment of a tuberculous joint in a faulty attitude, one should reduce the de- formity as gently as possible, either by gradual cor- rection by plaster-of-Paris, by traction in bed, or pos- sibly, if "the obstruction be not very resistant reduction under ether. If the disease has run its 698 REFERENCE HANDBOOK OF THE MEDK \l. SCI] \< ES Arthrology h nurse, and the fibrous ankylosis is very firm, an steotomy should be the corrective operation, fol- ,,,1 i,\ plaster-of-Paris. Fibrous ankylosis is the je. Bony ankylosis probably never follows tuber- losis in an adult, and only a mixed infection in i. Bony ankylosis requires an osteotomy ,,. its correction, with subsequent retention of the ,1, ,n pla ter for several months. Division of con- ted tendons may be :essary in addition. The ,.iiiinv should not lie done through the joint, for chiseling into an old tuberculous focus. Cases in Type 1. — After the disease has ached its quiescent stage, attempts to restore mo- in the joint are permissible. If the ankylosis be much may often be done by the use of me- apy, hot and cold douches, massage and pas- otion. Occasionally this may be preceded by reaking up the adhesions under an anesthetic and lien by putting the joint up in an entirely different ttitude in plaster for a month or two, especially ■ hip. The use of muscle flaps, animal membranes, has its advocates here as in bony ankylosis. Var- IUS surgeons have reported excellent results < /',/" II. — All attempts to increase motion orce here are decidedly contraindicated, and do In some instances the use of animal mem- iranes, or muscle flaps would seem indicated; in others obstructions may be chiseled away. In still rs an operation to produce bony ankylosis is able. If the surgeon will picture to himself the exact state [fairs in any old, diseased joint he will hardly go istray. It is the lack of exact knowledge which is . sponsible for most errors. Leonard W. Ely. References. 1 Allbutt'a System of Medicine, 1901. vol iii 2. Beitlike Zeitschrift fur klinische Medizin, 1912, S. 215. 3. Stiles: Journal of the American Medical Association, Feb. ,. 1912 4. Jansen: Archiv fur klinische Chirurgie, November, 1911. " Heck: Transactions of the Sixth Inter. Congress on Tuber- 190S. 6 Wallace Blanchard: Medical Record, May IS, 1912. 7 Hibbs: N V. Med. Journal, May 27, 1911; Journal Am. Med. Us'n. Aug. in, 1912. 8 Albee: X V Medical Journal. March 9, 1912. 9. Ely: Tuberculosis of the Adult Knee. Transactions of the >n on Surgery of the American Medical Association, 1912: loiat Tuberculosis, Wni. Wood & Co., 1911. 111. Stubenrauch: Munch, med. Woch., 1909, No. 36. Ahrens: Berliner klin. Woch., 1909. No. 48. 11. Hale White: Guy's Hospital Reports. 1902. 12. Nichols and Richardson: Journal of Medical Research, vol \\i. No. 2. 13. Nathan: American Journal of the Medical Sciences, June, 1909. I t. Llewelyn Jones: Arthritis Deformans. Win. W T ood it Co., IV Still: Allbutt's System of Medicine. 1901, vol. iii. See also Llewelyn Jones, Arthritis Deformans, 1909. 16. Albee: Surgery, Gynecology and Obstetrics, March, 1910. 17. Ely: Joint Tuberculosis, IVm, Wood & Co., 1911. Arthritis, Deformans. — See Rheumatoid Arthritis. Arthrology. — That part of anatomy which treats of the joints or connections between the denser parts if the skeleton. By means of these joints, or articu- lations, the skeleton, originally an apparatus for support, becomes an apparatus for locomotion. In its primitive condition the human skeleton is without joints, being represented, in the human fetus before the fifteenth day, by a simple non-jointed rod of condensed embryonic tissue called the notochord, a form permanent in the lowest vertebrate (amphi- is). This becomes ensheathed with tissue (Fig. 175), which changes to cartilage at regular intervals, thus becoming segmented (Fig. 476). Vestiges of the notochord are found in the adult as pulpy masses within the discs which unite the vertebra?. Else- where in the human body joints are formed in a similar way. I • laid down and then seg- mented by the differentiation of certain port into cartilage, which may aftei ify. The structures by which union is effected at thi joint may, therefore, be considered as the altered remains of the original skeletal matrix. Ground the segnu this matrix remains as fibrou ti ue, termed the perichondrium, becoming periosteum when ossifica- 1 1 1 ■ 1 1 i ;i ue . and i <• I ei □ the gments it occui ■ Notl "lion! Skeletogen- oua layer. I ii . I ,< moinsox uotochord. , 176. — Joints Derived from It. tChUd at birth.) Fio. 475. — Notochord without Fit; Joints. (Fetus fifteen days.) similar fibrous tissue, changing to fibrocartilage in certain cases. When in the form of bands, straps, or membranous sheets, these transegmental struc- tures are termed ligaments. They may unite not only the apposed ends of segments, but also Un- related sides. Sheets of this sort passing laterally from one bone to another in the same plane are known as interosseous membranes. Examples are seen between the radius and ulna, and between the tibia and fibula. The entire ligamentous system is closely connected with the fasciae, of which it may be considered a specialization. The prime characteristic of joints is, therefore, the movements which become possible by reason of seg- mentation. These movements vary according to the varying functions of the segmented members, and thus produce corresponding modifications of structure in the parts composing the joint. Upon these modifications the classification of joints de- pends. In all joints there is originally sufficient intersegmental tissue to permit slight and limited Periosteum Bone Intersutural \ ligament. J Periosteum Bone . . . Cartilage . suture. Fig. 47S. — Synchondrosis. motion. Such are called primitive or amphiarthro- dial joints. Examples occur in the adult between the bodies of the vertebra;. In the course of de- velopment the osseous or cartilaginous tissue of the segments usually tends to encroach more and more upon the intersegmental structure. If no alteration occurs in this, the joint becomes less and less movable until complete fixation ensues. It is then termed synarthrodial or immovable. Examples are seen in the adult skull. The process may be carried so G99 Arthrolojry REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Segment. far a* wholly to obliterate the joint. When the connecting substance is fibrous, the joint is termed a suture (Fig. 477); when cartilaginous, a synchon- drosis (Fig. 478). Strictly speaking, the union of the shaft of a long bone with its epiphysis is a s y nchondrosis. There being no. strain caused by movement i:i this class of joints, the peri- osteum [lasses over the inter- segmental tis- sue without thickening into ligamentous structures. Sutures are found only be- t w e e n bones that are developed in membrane, like those of the face and the vault of the skull. They form a special class of articulations, their function being not so much to permit movement of the parts united as to separate those parts and thus allow for the expansion of the inclosed structures. They are classified according to the manner of apposition of the edges; when these are nearly smooth the articulation is called an harmonia, when Segment i li.lllii'illll Fig. 479. — Formation oi the Synovial Cavity. Interarticular \ ligament. Vertebra. Rib. they are cut obliquely and override in a marked degree it is a sutura squa?nosa, when they interlock by toothed edges a sutura serrata, when an edge is re- ceived into a groove and en- sheathed, as occurs w-ith the sphenovomerine artic- ulation, it is a schindylesis. Some authors describe the articulation of the teeth with their sockets as an additional form of synostosis, giving it the name of gomphosis. In by far the greater number of cases the inter- segmental tissue of the joint becomes altered. Be- tween certain of the cells, vacuoles or small cavities form (proba- Synovial \ , cavities. / Fig. 480. — Costovertebral Joint. Synovial cavities. bly by the en- largement of the 1 y m p h lacunae of the connective tissue), and these join to- gether, mak- ing a larger cavity or cleft. The cells immedi- ately around the cavity form a secret- ing surface, the synovial membrane (stratum syn: oviale), the product of secretion being a glairy fluid called synovia. The membrane resembles the similarly formed serous membranes of the body, though it is not lined with endothelium. Like the serous mem- 700 m Interarticular cartilages. Fig. 481.- — Formation of Arthrodial Joints. branes, it is very vascular and is liable to suddei and dangerous inflammations. Synovial cavitie are formed not only between the apposed segment of a joint (Fig. 479), but also where tendons ml over hard surfaces, or where the skin is closel- applied to such surfaces and friction is frequent (se Bursce). Small and imperfect synovial cavitie exist in a few amphiarthrodial joints, but usualh the joints where such cavities occur are freely mov able throughout their extent, and are, therefore called diarthrodial. The intersegmental tissue mai Perios teum Bone Cartilage. Perios- ) teum. j Bone. Fig. 482. — Fully Developed Arthrodial Joint. not be wholly obliterated by the cavity. When the movement of the segments is perfectly regular and small in amount, it may remain as a central band with a cavity on each side and ligamentous structures surrounding the whole, forming a capsule or envelope. This is a peculiarity of the articulation of the heads of the ribs with the spine (Fig. 4S0). When the movement is such that the articular surfaces do no correspond, a synovial cavity is sometimes formed along the surface of each segment, leaving an inter- vening disc of fibrous tissue, which becomes partly cartilaginous and is then known as an interarticular Fig. 4S3.- -A Sesamoid (Knee Joint). Fig. 484. — Planiform or Glid- ing Joint (Patellofemoral). Sliding and coaptative motion only. fibrocartilage (meniscus articularis) (Fig. 481), Example, lower jaw joint. The disc may become thinned and disappear in the center, leaving a ring (Fig. 4S1 shows this in vertical section). This occurs in the knee-joint. Its complete disappear- ance is shown in Fig. 482. Joints may be formed under pathological condi- tions, the process being similar to that just described. After fracture the ends of the bone are first united by fibrous tissue, constituting an amphiarthrodial joint, which may remain permanently, or by process REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arlliniliity | repair be converted into synarthrodia! and finally jsappear; or, if mobility of the apposed ends be riot strained, there may be developed a false arthrodial tat with synovial membrane and ligaments formed ,,m the surrounding connective tissue. II, ,. action and relations of muscles are important in shaping and otherwise modifying joints. mounding they afford protection, and also lively assist the ligaments in holding together the i ends of the segments; differing in this, thai nsion can be adjusted to the stress placed on rments. They are invariably attached so as ,ort the articular surfaces with reference to ich other, never pulling them apart. Dislocations therefore more likely to occur if the force is pplied suddenly, before the muscles can be put in Transv. ngt Syn. cavities. |85. — Pivot Joint (Atlauto-epittrophic). A, top view; B, front view. Rotation only. etion, and are rare among professional athletes, v, (vantage is taken of this peculiarity of the muscles ng a dislocation, this being much more easily en the patient is taken off his guard, or ulution of muscular force is produced by an thetic. Expansions from the tendons of mils- strengthen and support the joints, uniting with ! iint capsule. When the strain put upon these insions is habitually great, as in case a tendon o er the angle made by the two segments, he connective tissue of the tendinous expansion is ■ to take on some denser form, as cartilage or >one. These appear as small nodular bodies known samoids, and possess true articular surfaces. patella is the largest and most notable example ■f these (Figs. 483 and 484). First meta- carpal. • . -Hinge Joint (El- Fir,. 487.— Saddle Joint (Thumb). tow). Angular motion in one Angular motion freest in two plane. planes. Comparative anatomy shows that a considerable number of the ligaments of adult joints represent muscles that have undergone a phylogenetic change in location and character. Thus the internal lateral ligament of the knee (lig. collateral tibiale) represents a former extension of the adductor magnus, the ex- ternal lateral ligament (lig. collaterale fibularc) an insertion of the peroneus longus, the great sciatic ment (lig. sacrotuberosum) an insertion of the biceps femoris. The shapes of articular surfaces depend mainly upon the direction and preponderance of the muscu- lar force applied to the segments. The simplest movement possible is the sliding of one nearly plane -urface upon another. This is the ordinary move- ment of the sesamoids. Joints in which this is the prevailing movement are called planiform or arthro- dial (Eig. -LSI). There are, however, no articular surfaces that are perfectly plane, there being no .-it na- tion where a pulling force i^ applied in a continuous straight line throughout the extent of the move- ment. For this rea on there i al o found in plani- form joints a slight rolling of convex surfaces on each other. This is called coaptation. When the sur- faces are markedly curved a variety of movements may take place. Motion around an axis passing lon- gitudinally through one of the segments is called rotation. Pivot joints (trochoides) possess only this Thumb. Fig. 4SS. — Pommel Joint (Wrist) . Angular motion in all planes. movement, and are exemplified in the atlanto-epis- trophic and proximal radio-ulnar articulations (Fig. 185). Bending the segments so as to alter the angle they make with each other is called angular movement. When lateral, to or from the axis of the body or limb, it is further distinguished as adduction and abduction; when forward or backward, folding or unfolding the segments, as flexion and extension. A hinge joint (ginglymus) is one in which such motion is allowed in a single plane only. The elbow is the best example (Fig. 4S6). The shape of the surfaces may allow free angular movement in some directions '?n\ Hip bone. Fig. 4S9.— BaU-and-Socket Joint (Hip). All movements. while limiting it to some extent in others. In the saddle joint (articulatio sellaris, Fig. 4S7), and the pommel joint (articulatio ellipsoidea, Fig. 48S), the motion is freest in two planes at right angles to each other. In the former, each surface is convex in one plane and concave in the other; in the latter, the sur- faces are reciprocally ellipsoidal. These two classes of joints allow all "movements except rotation, it being possible to perform circumduction or such swinging of the distal segment through a series of an- gular positions as to make it generate a conical sur- face. When the joint consists of a head nearly spher- 701 Arthrology REFERENCE HANDBOOK OF THE MEDICAL SCIENCES ical received into a closely fitting cavity, it i.s known as a ball-and-socket joint (enarthrosis, Fig. 489), in which great freedom of motion is allowed, all move- ments being possible. The following table shows how joints may be classi- fied according to a genetic system: Patellofemoral. Tibiofibular. Tarsal, except talonavicular and calcaneo- cuboid. Tarsometatarsal. Intermetatarsal. CLASSIFICATION OF JOINTS. Primitive Joints (Amphiarthroses). Without Synovial I With Synovial Cavity. Immovable Joints > Synarthroses). United by cartilage. Synchondroses. United by connective tissue. Suture. Freely Movable Joints (Diarthroses). Motion sliding or coaptu surface- nearly fiat. I'la.mform. Motion curvilinear, surfaces curved. XoN-PLANIFORM. Edges smooth. Edges Edges Edges en- Rotation Hakmonia. i iverlap. toothed. sheathed. only. StJTURA StJTURA SCHINDYLE- Pivot Joints. Squaw ISA Serrata. SIS. Angular Angular Angular All movements motion one motion freest motion all Ball-and- plane. in two planes. planes. Socket Joints. Hinuk Joints. Saddle Joints. Pommel Joints. The following is a list of the joints of the human body arranged upon the foregoing principles of clas- sification. As in all natural classification, perfectly clear and sharp distinctions do not exist, many joints being somewhat mixed, blending the characters of two or more classes. TABLE OF THE JOINTS. Order I. — Primitive Joints, or Amphiarthroses. Class 1. — Without a Synovial Cavity. Intervertebral — of bodies. Lumbosacral. Sacrococcygeal. Sternal. Class 2. — With an Imperfect Synovial Cavity. Sacroiliac. Interpubic (symphysis pubis). Order II. — Immovable Joints, or Synarthroses. Class 1. — Sutures. Joints between the bones of the skull, ex- cept occipitosphenoid and ethmovo- merine. Class 2. — Synchondroses. Occipitosphenoid. Ethmo vomerine. Chondrosternal of first rib. Costochondral. Order III. — Movable Joints, or Diarthroses. Class 1. — Planiform Joints, or Arthrodia. Intervertebral, of articular processes. Lumbosacral, of articular processes. Costovertebral (costocentral). Costovertebral (costotransverse). Chondrosternal, second to seventh ribs. Interchondral, sixth to ninth costal carti- lages. Sternoclavicular. Acromioclavicular. Radioulnar, distal. Carpal — between single bones. Carpometacarpal, except thumb. Intermetacarpal. 702 Class 2. — Pivot Joints, or Trochoides. Atlantoepistrophic. Radioulnar, proximal. Class 3. — Hinge Joints, or Ginglymi. Elbow-joint (humeroulnar). Phalangeal, of hand. Knee-joint (femorotibial). Ankle-joint (talocruraltibia and fibula with astragalus). Phalangeal, of foot. Class 4. — Saddle Joints. Carpometacarpal, of thumb. Calcaneocuboid, of ankle. Class 5. — Pommel Joints (Condyloid). Temporomaxillary (mandibular) . Atlantooccipital. Radiocarpal. Intracarpal (os magnum with semilunar and scaphoid). Class 6. — Ball-and-Socket Joints (Enarthrodia). Shoulder-joint (scapulohumeral). Metacarpophalangeal. Hip-joint (coxal = coxofemoral). Tarsal, (talonavicular). Metatarsophalangeal. An examination of the intimate structure of adult joints involves, (1) the ends of the segments (usually bones); (2) the articular cartilages which protect them; (3) the fibrocartilages which, when present, adapt the surfaces to each other; (4) the ligaments which prevent their separation; (o) the synovial membranes which by their secretion lubricate the surfaces. At joint surfaces pressure and movement occasion a modification in the ordinary structure of bone. The ends are enlarged and the surfaces are of ex- tremely compact tissue, protected by a layer of hyaline cartilage, the remains of the original cartilage from which the bone was formed. Acting as a buffer to break shocks and to prevent wear, it is invariably thickest where the pressure is greatest (see Fig. 482). Under normal conditions it never ossifies, although in old age and in persons of inactive life it becomes thinned and infiltrated with lime salts. Should it REFERENCE HANDBOOK OF THE MEDICAL 3CIENCES Artlirolncy & ly '% B M ■i i K'i V 7 . 3! egg ough, the bone becomes rapidly worn smooth burnated) and the joint is disabled. The super- nal cells of tlic cartilage are ■d. but in the deeper parts iey multiply in the line of the y j -. stress, and arc therefore I in columns perpendicu- , to the articular surface (Fig. which directions sudden may cause the cartilage to ilit. The fibrocartilages found joints arc composed of while tissue, n ith -parse elastic to impart the necessary siliency. Their usual form is ■ 'discs or rings attached ainlv to the more movable sen: either by. their edges (knee, or by the edge and one irfaoe (hip, shoulder). The be i completi enlarg- es the cavity on one side only ih&langi original capsular arrange- lent of the ligaments remains s in which the joint is e|| protected by muscles and ie strain is evenly distributed. a most joints, however, the ring much greater in >uie directions than in others, capsule becomes thickened > counteract it, forming bands Inch nave received special aines. Atmospheric pressure, .ting against the force of grav- sists in keeping thearticu- ir surfaces in apposition, thus re venting a constant strain pon the ligaments. An im- ortant office of the ligaments is to limit the motion f the segments and prevent the shocks which would otherwise occur from the sud- , den contact of bony surfaces. In some cases they greatly economize muscular force by holding the joint in a set position. Thus but little force is required to maintain the body erect, as it is sup- ported mainly by the tension of the ligaments of the spinal column, by the iliofemoral ligament at the hip, and by the posterior, lateral, and crucial ligaments at the knee; these lying always on the convex side of arcs subtended by the line of the center of gravity (Fig. 491). Owing to their function as limiters of motion, it follows that the position of greatest relaxation for all the ligaments of a joint is one midway between flexii in and extension. In case of the distention of a joint cavity by a morbid effusion, the patient involuntarily places the joint in such a position. Synovial membranes origi- nate as continuous and closed sacs, but over the articular surfaces, where pressure oc- curs, portions of them disap- pear; so that, at the latter part of fetal life, they merely line the capsule and extend m X- • Fig. 490. — Articular Cartilage. .4, Flattened cells; B, cells in column-; C, region infiltrated with lime; Z>, bone. (After Sappcy.) Fig. 491. — Ligaments Supporting Erect Posture. A, Anterior set; B, poste- rior set. but a shorl di tance upon the cartilages of the joint. In adult age they frequently are further extended by < ' ' ' m 1 1 1 1 1 1 r i i . ■ ; i ! Km u illi I he -\ ],.,\ ial cavities of neighboring bu ; -~ " . .-- and nil ci ii be- come re i " quenl and exten- more lax than the surroum ligaments, being thrown into folds to increase the blood supply and In pad 0U( i ~ , a isted in this by interstitial deposits of fat. Along the inter- articular lines lln vil- .} '. Inns pr or fringe-, some of which contain cartilaginous les (Fig. 492). It is at or near the joints that at \ ascuiar trunk- di an arrangement \\ hich is p bly connected with the centrip- etal development of bl I- vessels and the bud-like forma- tion of limbs in the embryo. The immediate supply of the joint is obtained from small vessels that anastomose freely with otn anot her. By them the collateral circulation is estab- lished when the main trunk is occluded. From these vessels a rich arterial network penetrates the capsule to supply the syno- vial membrane. Abundant cap- illaries lie in loops along the synovial folds, and by exudation from them the synovia is ap- parently formed. The articular cartilages and the compact layer of bone immediately contiguous are normally destitute of vessels, but capillaries rapidly extend into them during inflammation. The fibro- cartilages are stated by Sappey to contain vessels, and may therefore take an active part in inflammatory processes. Lymphatics are numerous near joints. Klein considers the joint cavity itself as a lymph space communicating directly with the lymphatics. The nerves of joints are dis- tributed mainly to the synovial membrane and the ligament- ous structures. It is probable that in these sit- uations special nerve endings e xist, as de- scribed by Krause and Xicoladoni, for it is difficult otherwise to ac- count for the peculiar sensi- bility of the structures. A ligament or a synovial membrane may be touched, cut, or pinched without giving much pain, but if it be stretched beyond its physiological limit, threatening the integrity of the joint, the suffering is excruciating, as is well known to those who have suffered from a FlQ. 492. — .Synovial Fringes. X 200. (Modified from Henle.) 703 Arthrology REFERENCE HANDBOOK OF THE MEDICAL SCIENCES sprain or a dislocation. Articular cartilage has no nerves, and the gnawing pain which occurs during its ulceration is probably caused by inflammatory products affecting the nerves of contiguous tissues. A remarkable law of correlation has been noted by Hilton with reference to the nerves of joints, viz., that they also supply the muscles w-hich move the joint and the skin over the insertion of such muscles; the whole apparatus being thus under the control of associated central influences. There is besides strong clinical evidence of this. Remak and Bene- dikt have pointed out the strong probability that many diseased conditions of the joints originate in irritable states of the spinal cord and of the sym- pathetic, and Charcot has published some cases showing remarkable atrophy of the muscles of a joint after an injury to the articular surfaces com- £aratively slight and inadequate to such a result. ocomotor ataxia is usually accompanied by joint lesions. For the anatomy of special joints see the following heads: Ankle Joint; Elbow Joint; Foot, Joints of; Hand, Joints of; Hip Joint; Knee Joint; Pelvis, Joints of; Shoulder Joint; Skull; Thorax; Wrist. Frank Baker. References. Besides the systematic work on anatomy by Quain, Gray, Allen. Morris, Piersol, Cunningham, Sappey, Cruveilhier, Henle, Hyrtl, Gegenbaur, Testut and Poirier, the following authorities have been consulted in preparing this article: Morris, William: The Anatomy of the Joints, London, 1S79. Turner: An Introduction to Human Anatomy, Edinburgh, 1SC7. .Marshall: Anatomy for Artists, London, 1SS3. Humphry: The Human Skeleton, including the Joints, London, 1S58. Henke und Reyher: Ueber die Entwickelung der Gelenke, Sitzungsber. der Wiener Acad, der Wissensch., Bd. lxx. Aeby: Der Bau des menschlichen Korpers, Leipzig, 1S71. Martin: Ueber die Gelenkmuskeln beim Menschen, Erlangeri, 1874. Meyer: Die Statik und Mechanik des menschl. Knochengeriistes, Leipzig, 1873. Fick, Rudolf: Handbuch der Anatomie und Mechanik der Gelenke, Jena, 1904-1911. Arthropathy. — Hypertrophic Osteoarthropathy. Unider this head it has until lately been the custom to nclude a variety of disorders with osseous hyper- trophy, more particularly of the ends of the long bones. General hyperostosis, osteititis deformans, acromegaly, and chronic pulmonary osteoarthro- pathy have been fully described by Freidrich, Paget, Marie, Emerson, and others and their forms of bony change and enlargement have been ascribed to syphilis, tuberculosis, disease of the hypophysis, and toxic influences. Hypertrophic Pulmonary Osteoarthropathy describes the condition more familiarly known as "clubbed fingers" which is found in patients suffering from pulmonary tuberculosis, or chronic disease of the lungs and of some other organs, such as bronchitis, bronchiectasis, empyema, pleurisy, malignant and gangrenous disease, as well as cirrhosis and congenital cardiac affections, and as the result of toxic absorption of various kinds. It is generally considered to be directly due to bacterial changes. The striking appearance of the fingers or toes of such patients is quite characteristic, being due to enlargement, which is found on both sides of the body. This is associated with changes in the nails which are incurved or flattened, with resulting de- formity. The root of the nails is elevated and when pressure is made there is the feeling as if fluid was be- neath. The nails are often brittle and sometimes cre- nated. The curving may be longitudinal, or again only the ends are bent downward. The onset of the disorder is attended by pain, which may be acute, and 704 by awkwardness of movement and stiffness, and an in ability to flex and close the hand. This is not due t muscular paresis but is rather the result of mechanics difficulty, due to the thickening of tissue and en largement. In aggravated cases there is a "paw like" appearance of the hand, which resembles tha of an animal. Sternberg and others have sought to classify th symptoms, but as Emerson 1 has pointed out," it j probable that the three divisions of this observe are but different periods of the disease. A shor acute stage ordinarily precedes the chronic, and it i Fig. 493. -The Hand in Hypertrophic Pulmonary Osteoarthro- pathy. quite possible that the remarkable bony enlargements that are subsequently found are but an advance in the conditions. Marie's cases, however, are so striking and the hypertrophy so general as to suggest acrome- , galy. All the large joints except the hip may he ' involved, and the inclusion of the vertebrae in the process may give rise to a kyphosis. The deformity of the hands in well marked and advanced examples is remarkable. The metacarpal joints seem to be the favorite site of the enlargement rather than the phalanges, but the whole finger may have a "drumstick" appearance. The skin is likely to be wrinkled and blue, tense and glossy. There seem to be variations in the amount and degree of the swelling proportionate to the activity and gravity of the purulent disease; in empyema the clubbing may appear in a few weeks and disappear when the pus is removed by paracentesis, and sub- sidence or cure of other conditions leads to diminution of the hypertrophy. The advanced disease when at all formidable, resembles acromegaly, but there are decided differ- ences. The mental condition of the latter as well as the polyuria and glycosuria, optical changes, peculiar enlargement of the lower jaw with prog- nathism, squareness of the face, prominence of the malar bones, elongated appearance of the upper lip, and swelling of the tongue are all features of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Arthropathy ■romegaly but not of the arthropathia condition, he nails are .small in acromegaly and neither cur\ ed ,r deformed. Hypertrophic pulmonary osteoarthropathy is some mes mistaken for arthritis deformans because of the presence of enlarged nodes in the fingers corresponding to the insert ion of t he extensor tendons, but the diagnosis should not be difficult. An examination with Roentgen rays shows the new bone forma- tion and considerable swelling. The ends of the long bom especially the ulna and tibia, are found to be increased in size. The disease is rarely found among negroes, and as a rule is a condition affecting adult males. The prognosis depends upon the course of the underlying dis- ease, for if the latter is cured, the enlargement often subsides. The pain and swelling of the fingers in the acute stage may be best relieved by moist heat, or by the e of a mixture of Fuller's earth and glycerin, which sold as a proprietary article known as antiphlogis- tic, or as cataplasma kaolini (U. S. P.). Arthropathies of Neurotic Orioin. — As far ick as 1S31 the elder Mitchell 2 first described i uliar joint troubles that affected individuals who id suffered from cerebral disease; and in 1846 Scott lison' of London more fully described these quote, presenting several cases in which the joints 194 Arthro- uliy of Right Knee I Buzzard.) the par iritis lie (iritis tie believed to be due to a condition of the ticular surface which results from the diminished itality of the paralyzed parts and the presence of ric acid, which under such circumstances acted as u irritative agent. hater, Brown-Sequard 4 and Charcot 5 directed I tention to the really important nature of such com- lications of organic paralysis, and the early researches I Alison, Durand-Fardel, Valleix, Grisolle, and have been collected and carefully considered y them. Buzzard later investigated these arthro- athies, especially in connection with locomotor :i\ill. It would appear that such morbid changes are sually associated with those forms of cerebral and final disease in which the sensory tracts are most ively invaded, though this is by no means the [variable rule. They are common in posterior ■ I sclerosis and rare in essential spinal paralysis, ii affection in which disorders of sensibility are the xception. They are rare in cerebral disease without ome ascending degeneration symptomatized by pain, ad the observations of Charcot regarding the ■ntral lesion would bear this out. Arthropathies nay be either cerebral or spinal, and the former are nuch more rare than the latter. They have been 1 'served in connection with coarse brain disease, such 3 softening with hemorrhage, tumor, or sclerosis; .iid are usually early symptoms of established cerebral ii i ttief; especially is this true in the matter of lemorrhage. After a period of from fifteen days to ■ oral months after the acute central trouble we find hat the joints of the paralyzed hand or foot become ected — the former more often (Charcot) — coin- idently with the contractions which mark the vdyent of rigidity and secondary degeneration. In uison's cases the knee and ankle were affected. Symptoms and Course. — The joint disturbances "'gin in one of two ways: (1) Suddenly, the large "hits being affected; (2) slowly, the joints of the land and foot being the parts attacked. In the first Vol. I.— 45 form there develops rather suddenly, within a few weeks, a swelling which is unattended by any marke I rise of tempera! ure al lea t by anj uch n would expect to find in an acute arthritis of purely rheu- matic origin. There are but little local heat and pain, but a great deal oi soreness when the limb is moved. Jarring produces only incon iderable sniveling. 1 have never met with the degree of pam described by Urown-Sequard. There is more Or fe pain produci I by pressure over the tendons, the sheaths of which seem to be involved. The joint is greatly swollen, the enlargement being made much more prominent in old cases by reason of the atrophy of muscular ma es in the vicinity. There seems to be a deep involvement of the joints and of adjacent parts, and though t here may be a synovitis, il is of a low grade, and, as Buzzard" has pointed out, there is really great. tumefaction, which characterizes the familiar form of chronic synovitis, in which there are three points of swelling, viz., above the patella, and on either side of the ligament um patella. The appearance of the affected joint is peculiar. The swollen limb. shows a duskiness and hardness in the beginning, and a cold, "white hardness" in the old cases. In some cases there is, after a few days or weeks, a .subsidence of the swelling, and I hen certain osseous changes, to be presently described, take place. The occurrence of spinal arthropathy may follow a variety of conditions. As has been pointed out by Mitchell, it may be connected with Pott's disease, with myelitis (Gull), with tumors of the gray sub- stance of the cord (Buzzard), with posterior spinal sclerosis (Charcot), and with traumatic injury of the cord (Vignes and Joffroy). Fig. 4U5. — Progressive Atrophy Resembling Acromegaly. According to Charcot the condition is often an earlj' complication of tabes dorsalis, but others think that it belongs to the late stages of the disease. It is quite true that in acute myelitis we may have a rapidly developing arthropathy, but in cases in which it is associated with a tumor of the cord or with locomotor ataxia the affection is a much more slow affair. Charcot believes that those arthropathies which affect the upper extremities in the disease under consideration are always secondary to others involving the lower extremities, and come only late in the disease as a result of extension of the morbid process. Buzzard reports a case which contradicts this, and the author has seen others. The enlargement in the chronic variety is slow, and a point is finally reached when deep destructive processes begin, the articular surface of the bones 705 Arthropathy REFERENCE HANDBOOK OF THE MEDICAL SCIENCES being worn away or absorbed, so that movement of the joint on manipulation will produce a peculiar creaking or cracking sound; and when the joint has for some time been the seat of the trouble it is com- mon for luxation to occur. The position of the ex- tremity upon the bed is peculiar, and the patient often presents a most strange deformity. Happily the arthropathy need not always go on to this stage and it occasionally happens that cures are made. On the other hand, the erosion and destruction may be very rapid: Charcot says: "Even within two weeks, or sooner, the 'craquements' may be detected, which indicate a profound alteration in the articular surfaces." At the end of three months the head of the humerus, in one of his cases, was found to be almost completely destroyed. Progressive Arthropathy. — There is a form of arthropathy of a progressive nature of which I have seen but one true case, and I do not know that any other has been reported. In the patient who came under my notice, a sudden swelling of both ankles occurred, with little or no pain, and in less than one year both thumbs and ring fingers became in turn affected, and ultimately both little fingers. The metacarpal joints were the seat of a hard and quite extensive swelling, with some general edema, more marked on the palmar surface. The patient could a' Fig. 496. — A, A', Right and left anterior horns; B, posterior gray commissure and central canal; C, anterior fissure; 6, b' , an- terior internal group of great cells; a, a', anterior external group of great cells;
  • 1 inches) of mercury and the maximum pressure eighteen cent i- meters (7. OS inches) as measured on a Pachon sphyg- ueter. The pulse was seventy. After a twenty- minute flight, during which, at the twentieth minute, a height of 1,100 meters (3,009 feet) was reached, the constant pressure was twelve centi- meters (4.72 inches) of mercury and the maximum nineteen (7.4S inches) ; the pulse had risen to eighty. The aviators were athletes in full training. The rise in pressure was less marked in fatigued aviators; but these showed cardiac palpitation and marked pulse acceleration (108). In one case after a flight of an hour, in which 1,000 meters was reached, the aviator manifested tachycardia — functional cardiac insufficiency with vertigo. Xo rise in blood pressure noted in aviators who flew at altitudes less than 500 feet. The cause of the blood pressure rise is probably the sudden descent to earth, in four to five minutes, from heights of 1,000 to 2,000 meters — in one-fourth or one-fifth the time required in ascending. At 2,000 meters elevation the atmospheric pressure i- 591 millimeters (23.3 inches) of mercury as against 760 millimeters (29.9 inches) at sea level. The circulatory system does not have time to become adapted to the change of pressure when a swift descent is made. There is also the dangerous fatigue of the circulator}' apparatus caused by high flying, which provokes increased and irregular heart action. A sound heart and supple arteries are absolutely essen- tial to aviation. It is considered that safety lies in height because the aviator, in case of accident, has time in which to get control of his machine: yet a sudden plunge from a height of several thousand fret is liable to strike the aviator helpless if not uncon- scious, and therefore to seal his doom. An examina- tion of the body of Maloney, in California in 190"), showed no broken bones or bruises sufficient to have caused death; evidently he was stricken with heart failure and died during his descent. Other manifestations of vial des aviateurs are sensation of intense cold; desire to urinate; irregu- larity in the movements of voluntary muscles and reflex aberrations — probably the expression of the combined effects of cold, accelerated heart beat, nervous tension, and fatigue. On landing there is an intense sensation of warmth over the surface of the body; the face is flushed; the eyes "sting." There is an almost invincible desire to sleep. Some of the symptoms noted in caisson workers find a counterpart in those reported by aviators. Of course only fit men should take to the air. Flights call for continuous effort, both physical and intellectual, under conditions to which the human organism is not as yet primarily adjusted. By way of prevention of all-too-frequent deaths some system of automatic stability should be invented (if such a thing were possible) so that an aeroplane may not dive to earth should an aviator become stricken while in flight. The aviator should, moreover, always carry a parachute, or wear a parachute garment so i hal he may jump or i umbl it aa end to earth in a iuld hi- machim !„ come unman- ageable. \\ here the mai : than 250 feel he had best bi I rapped in, a in B ground the mosl danger is from collisions or hoi i di\ is, from u hidi the a\ iator is like ■ uninjured h he cannot be flung oul when the crash comes, or even before, as was Moisanl < "'leans, Johm B. Ill A\icenna. — Abou Ali Ben AbdaUah Ebn Sina, better known to the Western World, thi ransmuta- tion oi the last two components of this name, as A\ icenna, was born in Bokhara, Turkestan, in August, 980 of the present era. He studied medicine and phil- osophy in Bagdad, and in dui time was looked upon by the Arabs a md Galen; they went so far, in fact, as to bestow upon him the appellation of I Fio, 540. — Aviceuna. Prince of Physicians. His "Canon Medicinse," a Latin translation of which was first printed in Padua, Italy, in 1470, was, for several centuries, the standard work on medicine. As a result of his luxurious habits and frequent excesses Avicenna contracted a dysentery that carried him off at Hamadon, Persia, in the year 1038, at the comparatively early age of fifty-eight A. H. B. Avon Sulphur Springs. York. -Livingston County, New Post-office. — Avon. Hotels. Access. — There are four railroad outlets. The town, located on two branches of the Erie Railroad, is made accessible from all points. Avon is in direct commu- nication with New York, 36j miles distant, Rochester twenty miles, and Buffalo, sixty-six miles. Man}' fine state roads emanate in four directions from the village. The village has a surpassingly beautiful location, nestled as it is in the charming and picturesque valley of the Genesee. The springs are on a somewhat lower level, about three-quarters of a mile from the village. The surrounding country is delightfully interspersed with charming lakes and streams. The Avon Mineral Springs were known to the Indians who resorted to them for the cure of skin diseases and so-called wast- ing disorders. The use of the Avon Springs for medic- inal purposes by white men dates from 1792. Those found to possess the greatest efficacy are known as the "Upper" and the " Lower" spring. The " Congress " and the " Magnesia" springs are also used to some ex- tent, the latter being the favorite for drinking. The following analyses show the chemical ingredients in one United States gallon of three of the springs: 821 Avon Sulphur Springs REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Solids Upper spring, J. Hadley, analyst drains. Lower spring. Dr. Samuel Salisbury, analyst. Grains. Ci ingress Hall spring, 11. M. Baker, analyst. Grains. Calcium carbonate. . . . Sodium sulphate Magnesium sulphate. S tdium chloride 8.00 16.00 84.00 10 00 IS. 40 29.33 13 73 57 I-' 49 61 9 25 21 02 27 61 19.07 29 . 1 1 8.41 Trace. Sodium sulphide. . . . 1 Calcium sulphide. . . ) 99.55 Total. 158.50 _'ll.-, .11 Gases. Sulphureted hydrogen Carbonic acid Oxygen Nitrogen Cubic inches. Cubic inches. Cubic inches. 12.00 5.60 Total. 10.02 3.92 . 56 5.42 19.92 27.63 22 H4 0.97 3.88 54.52 The well or New Bath Spring was discovered by R. K. Hickok in 1S35, while digging for pure water. The soil through which the excavation was made is hard blue clay, having a strong sulphurous odor. The temperature of this water is 46° F. Long's Spring has been in use since 1833. It rises from the surface of an alluvial deposit through the center of which passes what is termed Black Creek, a small stream having its rise some miles to the south. It is about a mile southwesterly from the upper spring. Following are the analyses of these two springs: New Bath spring, Long's spring, Dr. L. C. Beck, Dr. J. R. Chilton, analyst. analyst. Grains. Grains. 8.08 3.52 3S.72 13.10 109.05 3.27 19.31 5. 68 57.89 27.09 26.96 2.45 .81 Total 82.96 232.97 Gases. Cubic inches. Cubic inches. Sulphureted hydrogen 31.28 43.58 5.87 These waters are of the saline-calcic, sulphocar- bonated variety. The chemical constituents of the magnesia spring are believed to be quite similar to those of the lower spring, with, however, a greater proportion of magnesium sulphate. In consequence of the considerable proportion of this ingredient the latter two springs have valuable laxative and pur- gative properties. They thus become useful in dis- orders of the gastrointestinal tract accompanied by torpor of the liver and constipation. The water also produces an increased activity of the functions of the skin, and free diaphoresis often ensues. The water also possesses antacid properties and has been found of special benefit in cases of dyspepsia attended bv flatulence, heart-burn, and gastric catarrh. Both internally and in the form of baths, these waters have been found beneficial in cases of obstinate rheuma- tism, diseases of the urinary tract, and in various skin disorders. Facilities for all kinds of hot. cold, and electric baths are supplied. Emma E. Walker. Axilla. — See Shoulder. Azedarach. — Pride of China or India. China- berry Tree; China-tree. The bark of the root of Melia azedarach L. (fam. Meliaceoe). This is a fine, medium- sized, ornamental tree from India, but long cul- tivated in all the warmer parts of the world. It has delicate, twice pinnated leaves, fragrant clusters of lilac-colored flowers, and yellow globose fruits of the size of small grapes. Azedarach has been occasionally used for one or another purpose in various countries where it grows, and, in deference to a slight reputation in the Southern States was some time ago admitted to the Pharmacopoeia. It is now, however, excepting as an extemporary country medicine, nearly obsolete. The bark of the roi thus described: "Incurved pieces or quills, varying in size and thickness; outer surface red brown, with irregular, blackish, longitudinal ridges; inner surface whitish or brownish; longitudinally striate; fracture more or less fibrous: upon transverse section tangen- tially striate, with yellowish bast fibers; almost in- odorous, sweetish, afterward bitter and nauseous." It contains a whitish-yellow resin, which is claimed to be the active principle. Azedarach disturbs the digestive tract, causing, in large doses, vomiting and diarrhea. It is a fatal nar- cotic poison in still larger ones, but its qualities are not well known. It is usually given, however, for intesti- nal worms in decoction, or in syrup of the fresh root. Dose, four to eight grams oi. to ij.(4.0 to 8.0). Birds become stupefied by eating the berries, and fatal cases of poisoning by the seeds have occurred in India. H. H. Rusby. Azores. — The Azores or Western Islands lie about 2,000 miles from Boston, 1,400 miles from the Lizard Point, in England, and 800 from the coast of Portugal, of which they are a possession. The islands are nine in number and are divided into three distinct groups, about one hundred miles apart: Santa Maria and San Miguel forming the southeastern portion, Flores and Corvo the northwestern, and the remaining five the central division. The total area of the islands is about 1,000 square miles, and the population is esti- mated at 300,000. San Miguel is the largest island, being forty miles long and ten broad. Fayal and San Miguel are the two islands which are generally visited and with which there is the best communica- tion. One can reach them by steamers from New York and Portugal, and from Boston. The whole system of islands is of volcanic origin, and their out- lines in consequence are rugged and picturesque. The coast line is precipitous, and the central portion of each island rises in mountain peaks, which vary in height from 1.SS9 feet (San Miguel) to 7,613 feet (island of Pico). There are no natural harbors, and vessels lie in the open roadstead off the principal ports. A breakwater has been under construction for a long time at San Miguel, but it is not yet completed. The vegetation is rich and luxuriant, and both tropical and subtropical fruits — the fig, orange, banana, loquot, pineapple, prickly pear, guava, pome- granate, and lemon — grow in the open air. Flowers bloom in nearly infinite variety, and the gardens of San Miguel and Fayal contain an almost endless 822 REFERENCE HANDBOOK OF Till" Ml DI( \l. S( [ENCES Back, Diseases and injuries <>f iversity of tree, flower, and fruit. There an- no •wer than forty plants peculiar to the islands. Be- - these there are about 100 species which are iund in Europe, and 340 which are not found in ipe, but are common to Madeira, the Canary Is, and the Azores ( Roundell). The climate is a mild and moist marine one, and cry equable at all seasons of the year. The mean niiual temperature is ti'2 J F. The extremes are ; to be Sti° and 45° F. The range between win- in, I summer is from 10° to 15°. The night tem- ■ uro is generally not more than four degrees ■■ than the day. The summer is enervating at , and one is drenched with perspiration on the lightest exertion. The mean temperature for winter 58 for spring 61°, for summer 68 . and for autumn 1 . The three coldest months are usually Janu- nv. February, and March. In winter it sometimes chilly and damp, and one seldom leaves home without an umbrella. The humidity is so great that rail-paper will not adhere, and the veneering of fur- liture strips off. The mean annual relative humidity cinv— ix per cent, and for winter it is seventy- n per cent. The mean animal rainfall is 38.5 5. The wind blows with great force at timi s ind there are frequent storms. Ponta Delgada, in San Miguel, is the largest city of islands. It has a population of 25,000 inhabi- -. There are a good theater, a public library, lers of fine gardens, ancient churches and govern- ment buildings, public markets, etc. There are fortable accommodations here as well as at Horta. principal town of Fayal, and the food is generally Twenty-seven miles from Ponta Delgada by triage road, through beautiful and wild scenery, le Valle das Furnas, where are hot sulphur springs temperature of from 56° to 212° F. All contain sulphur, iron, alum, and silica in varying proportions. Besides the public bath houses, built by the Govern- ment and free to all, there are also private baths. The bath tubs are cut out of solid limestone or lava reck, and have taps for hot and cold water, the hot coming from the sulphur spring, and the cold from the water impregnated with iron. The bathing in begins in June and lasts for six months, dur- ing which time a large number of people frequent Las Furnas. The general custom is to hire lodgings and to take meals at the hotels. The various diseases for which these springs are beneficial are chronic rheuma- tism, which is almost invariably 7 benefited; paralysis, syphilis, skin diseases (especially eczema), dyspepsia, and internal troubles. Las Furnas itself is situated in the valley of the Furnas, which is the bottom of a vast crater of an extinct volcano. In this valley are the various boil- ing springs, with masses of white vapor hanging over them. A roaring noise is heard, as the hot gases le from the earth. The Caldeira Grande supplies the sulphur water to the baths, and is enclosed by a wall some six feet in height. The water in this tank- like enclosure boils in a most furious manner and with a great noise. It furnishes nineteen gallons per minute (Roundell). The ground about is covered with patches of white sulphur and alum, streaked with orange and red. In another part of the valley is the Boca do Inferno, or " Mouth of Hell," a dark pit of unknown depth filled with boiling mud, constantly- thrown up with a great smoke and noise. This mud is collected by the people and used as an external application in skin diseases. All the geysers or springs are said to boil most furiously when the wind is east. So far as the climate in general of these islands is concerned it is applicable to such cases as require a mild, equable, moist climate. It is therefore suitable for patients who are suffering from neurasthenia, from Bright's disease, from nervous affections, from hay fever, etc., and for those who are convalescing from the grippe and from other acute The water supply is from springs, wells, and and i^ generally good. From a personal visil to Fayal and Pico, the writer can testify to the charm and fascination of these strange islands with their ancii and primit uis, beautiful scenerj . and I ful and ever- varied walks, drives, and excut ioi -in hardly conceive of a more entrancing place for the lover of nature, or one more restful and refreshing for the weary and overworked. The only drawback is the long journey there, which is almost prohibitory to a sufferer from sea-sickness. I ■>!■ a very interesting and extended account of these islands the reader is referred to Mi . Charles Roundell's "A Visil to the Vzores, " and also to the two papers by Canfield and Junkin on " The Azores as a Health Resort." Edward O. Otis. Azule Springs. — Santa Clara County, California. Location, twelve miles wesl of San JosI, in the foot- hills of the Santa Cruz Range of mountains, 900 feet above sea level. Access. — Electric cars run from San Jos<5 to ' gress Springs, one and one-half miles from there to Azule. Trains on the Southern Pacific Railroad from San Francisco to Santa Cruz stop on signal at Azule Station, two and one-fourth miles from Azule. The following analysis was made some years since by James Howden, State Chemist: One Gallon- of "Water Contains: Grains. Sodium chloride 90 ss nesium chloride 18 18 Potassium chloride r_' 14 Magnesium carbonate 77 20 Sodium carbonate 50 ^ < :t Uium carbonate 9.00 Free carbonic oxide 152.24 Total 431 . 12 This is a natural seltzer water. The water pos- sesses antacid, aperient, diuretic, and tonic properties. There are cottages for rent, and camping privileges. Emma E. Walker. Babesia. — Pyroplasma, Pirnplasma. A pathogenic genus of Sporozoa, order Hiemosporida. B. hominis causes Rocky Mountain tick fever, "spotted fever. " or " piroplasmosis hominis" in man This disease appears to be local in distribution, occurring in spring and early- summer in the mountains of Montana and Idaho, and may be transmitted to man, rabbits, guinea-pigs, and monkeys by ticks. The Texas cattle fever is caused by B. biaeminum a sporozoan carried by the tick, Boophilus bovis. In this case some of the blood sucked by the mother is enclosed with the eggs she lays so that young are born with the fever infection if the blood contained it. East Coast fey r er is caused by a similar sporozoan. See Protozoa. A. S. Peakse. Bacillus. — A genus of the family Baeteriacea?, com- prising cylindrical rod-shaped or oval forms, with peritrichal flagella, often with endospores. Division occurs in the transverse plane and the individual cells may remain attached, forming chains or threads of varying lengths. The term bacilli is often incorrectly used to denote the Schizomycetes, or fission-fungi, in general. Back, Diseases and Injuries of the. — In wounds and injuries of the back, as in those of the chest and abdomen, we have to consider first, the injury inflicted upon the superficial tissues, and secondly, that sustained by the subjacent organs. The wounds of the superficial structures present no characteristics 823 Back, Diseases and Injnri.- of REFERENCE HANDBOOK OF THE MEDICAL SCIENCES peculiar to this region. The back is, however, by reason of its numerous articulations, very liable to sprains. These may vary greatly in degree, and since it is impossible always to determine at the moment how serious the injury may have been, a sprain of the back should never be neglected, but should be watched and treated as though it were an important affair until its true nature is ascertained. The spinal ligaments may be simply strained, or they may be ruptured; or an injury of the back, which may at first seem of comparatively slight moment, may be accompanied with fracture or dislocation of a vertebra, with con- sequent compres- sion or concussion of the cord; or compression may be caused by hem- orrhage within the canal. The loca- tion of the sprain may be indicated by a swelling, or there may be no external evidence whatever of in- jury. Sprains in the lumbar region are not infre- quently followed by hematuria, but this symptom, al- though apparently so serious, is usu- ally of little mo- ment and disap- pears without any further complica- tion. The treat- ment of simple sprains, without injury to the cord, is essentially rest in bed with, later, coun terirritation over the affected region. Neuroses of varied character are very liable to follow concussion or other violence applied to the spine. The fre- quency with which nervous symptoms follow spinal injuries received in railway accidents led Erichsen to apply the term "railway spine" to such conditions. Whether the resultant neurosis is spinal or mental in essence is still sometimes a matter of dispute, with the weight of opinion inclining to the latter. (See Neuroses, Traumatic.) Penetrating wounds of the back are serious because of the injury inflicted upon the internal organs. In determining what organs may have suffered in any particular case, if we leave out of consideration for the moment the direct evidence afforded by the symp- toms, it is necessary to ascertain the nature of the wounding object, whether a knife, a bullet, etc., and also the direction of the wound. If a knife or other sharp instrument have been used, it should, if possi- ble, be ascertained how deeply it has penetrated, and whether the blow was struck from above, from below, or laterally; and if it be a gunshot wound, whether the weapon was discharged at close quarters, or whether the ball was nearly spent before pene- trating the back. It must not be forgotten also that the course of a bullet is often very erratic, and that, while it has seemingly penetrated the abdominal or thoracic cavity, it may, in reality, have glanced along a rib and be lodged in the muscles on the other side of Fig. 541.— The Relations of the Thor- acic and Abdominal Viscera, as seen from Behind. The stars indicate the location of the spinous processes of the seventh cervical, fourth and ninth thoracic, and third, and fi.th lumbar vertebne. (Modi- fied from Quain.) the back, or anteriorly. The position of the person at the time the injury was received is also to be con- sidered, since, when he is in the recumbent position or when stooping, the liver and some of the other organs are higher than when the person is sitting or standing erect. And another point to be determined in certain cases is the time at which the wound was received, whether after a hearty meal or while the individual was fasting. Fig. 541 represents diagrammaticaJly the ordinary position of the thoracic and abdominal viscera, but of course only in a very general way. The movements of the back are chiefly in an anteroposterior and lateral direction, though a slight amount of rotation is also possible. In the upper portion but little motion of any character takes place, and it is in the lumbar region chiefly that flexibility exists. A "'stiff back" may be due to chronic rheumatic arthritis of the spine, to Pott's disease, to spinal ankylosis, to inflammation or rheumatism of of the spinal or abdominal msucles, to psoitis, or to a sprain. Pain in the back is a common symptom, and may be due to any one of a variety of conditions, as 6.3. neurasthenia, muscular rheumatism, rhachialgia, Pott's disease, nephritis, cystitis, renal or vesical calculi, an accumulation of gas in the intestines, uterine disease, myositis, or hysteria. (See Lumb and Spine, Diseases of the.) The back is frequently the seat of tumors and other swellings, the nature of which it is important, while at the same time not always easy, to determine. V, e have, in the first place, the ordinary fatty and fibrous tumors, naBvi, epitheliomata, and sarcomatous and sebaceous tumors (the last two rarely), the diagnosis of which offers nothing peculiar in this region. Spi bifida is a not very uncommon affection, and is usually not difficult of diagnosis. (See Spina Bifida.) Ab- scesses of the back are by no means rare. They be idiopathic, or the result of traumatism, or the pue from an empyema may point posteriorly. It should not be forgotten that an abscess, pointing in the back or elsewhere, may be referable to spondylitis even though there be no angular curvature visi The kyphos of Pott's disease can hardly be mistaken for anything else, but in lateral curvature with so- called rotation, the resulting prominence of the muscles on the side of the convexity might, if ci lessly inspected, be taken for a tumor. Sometimes this apparent tumor is at some distance from the spine, and is the expression of a secondary deformity and bulging of the ribs. The back is the ordinary seat of bed-sores, whether occurring from pressure or of neurotic origin. There is no other condition with which a bed-sore is liable to be confounded, though it is not always an easy matter to discriminate between the different varic of this distressing affection. (See Decubitus.) Diseases of the skin and muscles of the back do not differ in any essential points from similar affections in other parts of the body, and their consideration need not therefore be entered upon here. T. L. S. Bacon, Francis. — Born at New Haven, Connec- ticut, October, 6, 1831. His father was a distin- guished theologian, Rev. Dr. Leonard Bacon. He studied medicine at the Yale Medical School, and received the degree of Doctor of Medicine from that institution in June, 1S52. Very soon after the termination of his medical course he went to Galves- ton, Texas, where he had charge of the hospital of that city. He remained there for several years, until the outbreak of the Civil war. During the Civil War he served first as Assistant Surgeon, and afterward as Surgeon, in one of the Connecticut regiments. He was then appointed Medical Inspector in the Department of the Potomac, 824 REFERENCE II. WDM < < U- Till: MLDICAL scl i:\TES Bacteria and, still later, Medical Director of the Department of the Gulf, with headquarters at New Orleans. \t the close of the war he resigned his commission : i id returned to New Haven, having been invited to fill the Chair of Surgery in the Vale Medical School, upon the retirement of Dr. Jonathan Knight. In 1906 University conferred upon liim the hono title of Doctor of Science. He died in New Haven on Vpril 26, 1912. Dr. Bacon made very few contributions to medical literature. He was not fond of writing, and his very large surgical practice left him scarcely enough time for needed rest and recreation. The various official positions, however, which he held — first during the Civil war and afterward during his life in Nev Haven — testify sufficiently to his ureal ability as an executive officer and as a surgeon, and to the high esteem in which he was held by his professional brethren and by his fellow citizens. Bacon, Francis, Baron Verulam, Viscount of Saint Albans. — Born in London, January 22, 1561. His lather, a celebrated jurist and one of the most influential advisers of Queen Elizabeth, gave him every possible educational advantage. From his earliest childhood young Bacon manifested unmis- takable evidences of possessing a mind of a superior order. During his course of studies at the University of Cambridge he made astonishing progress in all the departments of learning. Already at the early age of sixteen he displayed remarkable independence of character, as evidenced by the fact that, in complete disregard of the philosophical views held at that time, he did not hesitate to begin laying the foundal of a new general system of philosophy — the one, namely, which subsequently brought him imperish- able fame. After completing his university career in 1576, he visited Paris in company with Sir Amyas Paulet, Queen Elizabeth's ambassador at the Court of Trance, remaining there until the death of his father in 1579. While he was still in Paris, be- ing then not nineteen y.ars of age, Bacon began writing his essay On Life and Death, " Historia vitae et mortis" (not pub- lished, however, until 1623 in London)— that one of his treat- ises which touches more especially on purely medical science than does any other of his writings. The Dictionnaire Histor- ique de la Medecine makes the following analysis of this essay: "In animated bodies there exists, as Bacon assumes, a spirit which is purer than air and less ener- getic than fire, and which is held fast in the tissues by substances of a viscous nature. This spirit (or prin- ciple of life) gradually, in the course of time, consumes the bonds which hold it fast and is thus eventually and Completely set free — this is the direct cause of natural death. One may hope to prolong life by moderating all vital activities, by avoiding the different impressions made by the air, by restoring the humors of the body to their normal state, by bringing back to the viscera the vital spirit which they may have lost, and by closing the pores or channels through which it tends to make its escape. These ends may be attained by a proper degree of repose, by a somewhat debilitating regimen or diet, and by the use of the two drugs — Fig. 542. — Francis Bacon. and opium. I bi ii Bacon cites, in Bupporl of I heory, mi tances of m great longer ity. He also i ntion to thi fact that the longest duration of in those animals which have a long period ol ge 'at ion and which are alow in attaining their full growth. I i' illy, he describes t he < Mil. Is oi life, and i xplains the phenomena of death. The most important of Bacon's works wire, in addition to those j tioned, "The '■ on hi of Learning." 1605; "Novum Organum, indicia vera de interpretatione," 1620; and "De Augmentis Scientiarum," L624, the latter being an id ami revised Latin translation of the earlier work mi "The Advance nt of Learning." Bacon died April 9, 1626. A. II. B. Bacteria, Pathogenic. — The Schizomycetes or Bac- teria are among the smallest and at the same time the most int cresting of all known living organisms. \\ hile most bacteria are harmless — some of them, indeed, being of the greatest use in ll 'otiomy of nature, by producing the decomposition of dead animal and vegetable matter, without which life on the earth would be impossible — others are the cause of various infec- tious diseases in man and animals. Bacteria are very widely distributed in nature, and are present in the air, water, soil, and also in the food and bodies of animals. Historical Review of the Development of Bacteriologt. — Although most of the important discoveries of bacteria in their relation to disease are of comparatively recent date, from the earliest days of medicine, and long before these microorganisms were known to exist, minute living germs were thought to be concerned in the production of many disea Before entering, therefore, into a detailed considera- tion of pathogenic bacteria, it may be interesting and instructive to review briefly the more important -tips which lead up to the development of bacterio- logy as a science. The first authentic observations of living micro- organisms of which there is any record are those of Athanasius Kircher, a Jesuit priest, in 1659. The compound microscope dates from 1590, but this observer was the first to find in putrid meat, milk, vinegar, cheese, etc., minute living organisms or "worms," invisible to the naked eye, which he con- cluded must be the cause of putrefaction. Kircher, however, did not describe the form or character of these "little worms," and with the microscopes in use in his day he probably did not see bacteria, as we now understand them. Nevertheless, his observa- tions seemed to substantiate the view- that infective diseases might be caused by .substances which, introduced into the body, give rise at first to no symp- but increase till they bring about disease; the opinion held at that time by many physicians being that if putrefaction is produced by living organisms outside the body, when these organisms are found in the blood, etc., they must necessarily cause putre- faction there also. Not long after this, in 1675, Anthony van Leeuwen- hoek, a citizen of Delft, Holland, a linen draper by trade, who practised the art of grinding and polishing lenses, constructed a microscope with which he was able to observe in rain water, in putrid infusions, in human saliva, in intestinal evacuations of man and animals, and in the scrapings between the teeth, numbers of living "animalculae" as he called them, varying in form and size and in the character of their motion. Of these he gave descriptions and drawings which are remarkable for their accuracy, considering the imperfect optical instruments at his command, and there is little doubt that he really saw some of the larger species of bacteria, probably spirilla. Leeu- 825 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES wenhoek made no attempt to assign any importance to these organisms regarding the role they might play in relation to disease, his work being conspicuous for its purely objective and unspeeulative nature. But his contemporaries and those who immediately succeeded him seized upon the idea of these animal- cules causing a great number of diseases, even in cases in which they were not found, reasoning from analogy that they must be present, until there arose a veritable craze of the germ theory of disease or contagium animatum. Then later followed a reaction, and the idea for a time was ridiculed out of existence. And so throughout the history of medicine this theory continued to be often asserted and as often again denied, on speculative grounds, until well into the present century, when the question was finally settled by actual observation and experiment. Among those who at this early date (the end of the sixteenth and beginning of the seventeenth century) held to the doctrine of contagium animatum were Lange and Hauptmann, who shortly after Leeuwen- hoek's investigations advanced the opinion that puerperal fever, measles, smallpox, typhus, ple- urisy, epilepsy, gout, and many other diseases were due to animal contagion. And in 1701 Andry and Linne assumed the same origin for syphilis, and Lancisi (1718) for malaria. Antonius Plenciz, a physician of Vienna, who published his deductions in 1762, maintained that not only were all infectious diseases due to microorganisms, but that the infective material could be nothing else than living animals or plants. On these grounds he endeavored to explain the variations in the incubation period of different diseases. He insisted also that special germs were concerned in the production of each infectious disease. Plenciz believed, moreover, that these microor- ganisms were capable of multiplication in the body, and suggested the possibility of their being conveyed from place to place through the air, etc. Besides these deductions he also made original in- vestigations into the processes of putrefaction and fermentation, and having found animalcules in all decomposing material, he became so thoroughly convinced of their causative relation to these processes that he formulated the law tha.t decomposition of animal and vegetable matter takes place only by means of and through the increase of living organisms. Still all this was entirely a matter of speculation only, unproved by direct experiment; but the theory advanced was so plausible and the arguments used in its support were so logical and convincing, that in spite of great opposition and ridicule it continued to gain ground, and in many instances the conclusions reached by these early philosophers have since been shown to be correct. Meanwhile the question which most attracted the interest of all investigators into the cause of in- fectious diseases was: What is the source of the microorganisms which are supposed to produce these processes? Are they the result of vegetative changes in the substances in which they are found — the theory of generatio oequivoca, or spontaneous genera- tion; or are they reproduced from similar preexisting organisms — the vitalistic theory? This question is intimately connected with the investigations into the origin and nature of fermentation and putrefaction, for it was in these experiments that the theory of spontaneous generation was overthrown and the germ theory established. Of those who most vigorously advocated the idea of generatio oequivoca was Needham, who, in 1749, at- tempted to prove experimentally the truth of his opinions. He placed a grain of barley in a watch glass containing water, covered it carefully, and allowed it to germinate. On later examination he found living microorganisms present which he main- tained were the effect, not the cause, of the decompo- sition and due to vegetative changes in the grain itself. Again, he boiled meat infusions and kept them in tightly corked flasks; in these also living organisms developed. As all life must have been destroyed by the boiling, and the closed flasks shut out appar- ently everything from without, Needham concluded that the organisms present could have been pro- duced only from the dead material by spontaneous generation. This conclusion seemed indeed irrefutable at the time, but Bonnet, in 1702, suggested that possibly there were certain germs which were able to resist the boiling temperature, or that the flasks were not so tightly closed that no germs could enter. Then in 1769 Lazarus and Spallanzani showed experimentally the falseness of Needham's results, by demonstrating that if putrescible infusions of organic matter were placed in hermetically sealed flasks and boiled for an hour the infusions remained sterile; neither were living organisms found in the liquids, nor did they decom- pose. It was objected to these experiments that the high temperature to which the liquids were subjected so altered them that spontaneous generation could not occur. Spallanzani then simply cracked one of the flasks a little and allowed air to enter, when organisms and decomposition again appeared in the boiled solu- tions. Again it was objected that in excluding the oxygen of the air by hermetically sealing the flasks the essential condition for the development of putrefaction, which required the free admission of this gas, was interfered with. This objection was met by Schultze in 1836, who showed that the air could have access to sterilized infusions without causing putrefaction, if it were first freed from germs by passing it through strung sulphuric acid. Schwann effected the same thing in 1837 by passing the air through red-hot tubes; and Helmholtz in 1843 repeated and confirmed these experiments with calcined air. Again the point was raised that the heating of the air had perhaps brought about some chemical change which prevented the production of putrefaction. Schroeder and von Dusch then showed, in 18.54, that if the air was fil- tered through cotton wool, by simply placing stoppers of this material in the mouths of the flasks before boiling — a device which has since proved of inestim- able value in bacteriological work — the contained liquid was incapable of producing putrefaction. Similar results were obtained by Hoffmann in 1860, and by Chevreul and Pasteur in 1861, without a cotton filter, by drawing out the neck of the flask and bending it downward, the mouth being left open. Here the force of gravity prevents the suspended bacteria in the air from ascending, and there is no current to carry them upward into the liquid. Tyndall later (1876) showed by his investigations upon the floating substances in the air that in a closed chamber in which the air is not disturbed by currents, all sus- pended particles settle to the bottom, the super- incumbent air being optically pure. He demonstrated beyond all doubt that the presence of living organisms in decomposing fluids was always to be explained either by the preexistence of similar living forms in the fluid or upon the walls of the vessels containing it, or by the liquid being exposed to air which was con- taminated by organisms. But still another matter required explanation. A certain percentage of the experiments with infu- sions, which had been boiled for a considerable time and carefully protected from subsequent contamina- tion, would now and then fail despite every precaution. Bonnet in 1762 had suggested the explanation of this, on the assumption that some organisms were perhaps capable of withstanding the boiling temperature, and still grow when the infusion cooled. Then Past- eur found that he could sterilize milk only at a tem- perature of 110° C, and later (1865) showed that the organisms which resist boiling temperature are re- productive bodies, now known as spores. But it was not until 1876 that the nature of spores was care- 826 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria fully studied and explained by Cohn, and afterward confirmed by Koch. These investigators proved thai certain rod-shaped bacteria possess the power of passing into a resting or spore stage under peculiai conditions of growth, and thai when in this stage they are much less susceptible to the injurious action of higher temperatures and other deleterious influences than when in their normal vegetative con- dition. With this discovery the question of spontaneous generation was finally settled in the negative and the germ theory established. If living microorganisms, ie of them capable of producing the more resistant res, were present in the air, soil, water, etc., it was easy enough to understand how irregularities occurred in previous experiments; nor eon 1.1 1 here longer beany doubt that bacteria were the cause, not the effect, of fermentation and putrefaction, and possibly also of iase. But, in the mean time, little or nothing had been accomplished in the systematic classification of bacte- ria, although their forms were zealously studied tniero- scopically as matters of curiosity. The first attempt at classification was made by Midler, of Copenhagen, in 17SH, who divided microorganisms into two main divisions — monas and vibrio. But he, like all the earlier naturalists, owing to lack of sufficiently power- lid microscopes and inadequate knowledge of the biology of bacteria, fell into grave errors of classifica- tion. Thus various motile organisms, which are now ignized to be of vegetable origin, were commonly included among the infusorians or unicellular animal organisms. Even Ehrenberg, in 1838, and Dujardin, in 1841, though their work shows considerable pro- gress in this direction, failed to arrive at a satisfactory classification of bacteria; these authors dividing bacteria into four orders — bacterium, vibrio, spirillum, and spirochete — and including them with the in- fusorians. Perty, in 18.52, was the first apparently to draw attention to the vegetable origin of bacteria; and Robin, in 1S53, then suggested their relationship to the alga*. But it remained for Cohn in 1S54, and Naegelt in 1S.57, to bring anything like system into the confusion which had previously existed regarding the classification of bacteria. It was Naegeli who estab- lished their resemblance to the fungi, in that they were chlorophyll-free plants, and gave them the name of Bchizomycetes or fission fungi to indicate their mode of reproduction; and Cohn confirmed and emphasized this relation of bacterial species to the vegetable kingdom, and first employed the term bacteria for the entire class of these microorganisms, studying their various groups more carefully. At the same time, the physiological properties of bacteria were studied, with as much, if not more, success than their morphology and classification. Stimulated by the discovery of the microbic origin of the processes of fermentation and putrefaction — the specific cause of one form of which, alcoholic fermentation, was found by Latour and Schwann, in 1837, to be the yeast plant (Saccharomyc.es cerevisice) — the study of the causal relation of microorganisms to disease was again taken up with renewed vigor. So far the bacterial source of infectious diseases was founded only on hypothesis, and although belief in this theory was much strengthened by the foregoing experiments, it had not yet been proved. It was not long, however, before the necessary proof was forth- coming at least for one disease, for in the same year as Schwann's discovery of the yeast plant, Bassi dis- covered that a fatal infectious malady of silkworms was due to a parasitic microorganism; and later a similar origin was found for various infectious dis- eases in grains, potatoes, etc. Just about this time, too (1S40), Henle published his "Pathological In- vestigations," in which he described the relation of bacteria to disease with remarkable clearness and precision, the weight of the opinion of this great authority contributing much to i interest i doctrine of infection. Although Henle failed to organisms in 111.' 1 1 ue in various infect this did not lead him to change his opinion, for he con- tended rightly that there were no means at that time of distinguishing between tissue cells and bacteria. Nor did he consider the presence of microorganisms alone sufficient proof of their etioloi ition, but postulated the conditions later confirmed to the letter by Koch, which must be fulfilled to dec that a disease is due to a specific microorganism. These conditions were constant presence in the dis- ease, isolation, and evidence of tne infectious nature of the isolated germ by inoculation. Similar con- clusions were also reached by Mitchell, independently, reasoning by deduction. Very soon after this it. was shown experimentally that microorganisms were thi causi "f various skin diseases in man, as favus and ringworm. About this time also. Pollender (1849) Observed certain rod- shaped bacteria in the blood of animals dying from anthrax or splenic fever, and he was followed by Davaine (1850); but the e observers attached no special significance to their discovery until Pasteur made public his researches in regard to fermentation and the role played by bacteria in the economy of nature. Then Davaine resumed his studies, and in 1S63 e-tabli.-hed by inoculation experiments the bacterial origin of anthrax — which was later con- firmed by Pasteur, Koch, and others. Schwann had already shown the connection be- tween certain organisms and alcoholic fermentation, but Pasteur, in 1857, deserves the credit of finally establishing the fact that the various kinds of fermen- tation — lactic acid, butyric acid, acetic acid fermen- tation, etc. — are all caused by microorganisms, which not only differ in physiological action, but are charac- terized by morphological and biological peculiarities. In this connection Pasteur also made the discovery of certain bacteria which were incapable of growth in free oxygen, assigning to them the name of anaerobes to distinguish them from the aerobes, or those re- quiring the presence of free oxygen. Others, again, he found were capable of growth, either with or with- out free oxygen, and these he called facultative anaerobes. Pasteur's investigations demonstrated the fact that since bacteria are the cause of fermenta- tion and putrefaction, they are necessary for the life of plants and animals, for without their agency the higher plants, incapable of feeding upon the complex substances of dead animals and plants, would die if these substances did not undergo decomposition into their elements through the instrumentality of bacteria; and thus the earth would be unin- habitable. The next important discoveries related to the cause of infection in wounds. Lemaire, following up the experiments of Pasteur, had observed that when car- bolic acid was added to putrescible substances fer- mentation was prevented, and he came to the conclu- sion that the carbolic acid destroyed the germs which produced fermentation. The processes of fermenta- tion and suppuration he believed to be analogous. If the addition of carbolic acid solution inhibited fermentation, why should it not be applicable to the prevention of suppuration in wounds? Upon these suggestions Lister now (1863-70) instituted his famous antiseptic treatment of wounds, which has led to such brilliant results in modern operative surgery. The publication of Lister's work exerted a powerful influence upon the general recog- nition of the germ theory of infectious diseases, and had much to do in lessening the number of its oppo- nents. Then Rindfleisch, in 1S66, and Waldeyer and von Recklinghausen, in 1871, drew attention to the constant occurrence of microorganisms in pyemic processes resulting from wound infection — observa- tions which have since been amply corroborated by 827 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES others for all suppurative processes under whatever condition produced. From this time on followed, in comparatively rapid succession, the discoveries of a number of microorgan- isms as the cause of various infectious diseases. In 1S73, Obermeier announced having found in the blood of patients suffering from relapsing fever a minute spiral, motile organism — the Spirochete obermeieri — which is now recognized as the specific infective agent in this disease. In 1S78, Koch published his im- portant work on traumatic diseases. In 1879 Hansen reported the discovery of bacilli in the cells of leprous tubercles, which, from subsequent investiga- tions, are believed to be the cause of leprosy. Neisser, in the same year (1879), discovered the "gonococcus" in gonorrheal pus. In 1880, Eberth and Koch, independently, observed the typhoid bacillus, which Gaffky, in 1884, proved to be the cause of typhoid fever. In the same year Pasteur published his discovery of the bacillus of fowl cholera and his investigations upon protective inoculation against this disease and anthrax. Sternberg and Pasteur, also in the same year, independently observed a patho- genic microorganism in human saliva, which was subse- quently (1885) proved by Fraenkel and others to be the organism most commonly associated with acute lobar pneumonia and now recognized as the usual cause of that disease — the Diplococcus pneumonice. In 1881, Koch made his fundamental researches upon pathogenic bacteria, which form the basis of our modern bacteriology. He introduced solid culture media and the "plate method" for obtaining pure cultures, and showed how different organisms could be isolated, cultivated artificially, and by inoculation of pure cultures into susceptible animals made, in many cases, to reproduce the specific disease of which they were the cause — thus carrying out Henle's suggestions. It was also in the course of this work that the Abbe system of substage condensing appara- tus on the microscope, and the Ehrlich-Weigert method of staining bacteria for microscopical prepara- tions were first generally used. In 1882, Koch published the discovery of the tubercle bacillus. The same year Pasteur made his investigations upon hog erysipelas; in this year also his communication upon rabies appeared. In 1S82 also Loeffler and Schiitz discovered the bacillus of glanders. In 1884 Koch discovered the spirillum of Asiatic cholera, the "comma bacillus." This year, too, Klebs and Loeffler dis- covered the diphtheria bacillus. Rosenbach also, by the application of Koch's methods, fixed definitely the characters of the various pus-producing organisms. And the same year Nicolaier discovered the tetanus bacillus which Carl and Rattone afterw-ard showed to bs the true cause of the disease, and Kitasato obtained in pure culture. In 1892, Pfeiffer discovered the bacillus of influenza; and finally, in 1S94, Kitasato discovered the bacillus of bubonic plague. This closes our brief historical sketch of the develop- ment of bacteriology, including all the more important facts which are of special interest to physicians. But no review of the progress which has been made in this branch of science would be complete without reference to the recent discoveries of antitoxins in the treatment of diphtheria and tetanus, the protective inoculations against rabies, cholera, the plague, etc., and the peculiar reactions of the blood serum of per- sons ill with infectious diseases. These discoveries, in which the names of Pasteur, Koch, Behring, Kitasato, Roux, Pfeiffer, Gruber, and Widal are the most prominent, not only mark an epoch in the history of bacteriology in relation to medicine, but have served to establish beyond all doubt the microbic origin of many diseases, the cause of which was until then in dispute. Attention has, moreover, been directed of late to the group of animal micro- parasites, the protozoa — to which class belong the Plasmodium malaria and the Amoeba coli, the cause 828 of malaria and epidemic dysentery, respectively which may prove to be the source of infection in many affections the origin of which is still unknown, as the exanthemata. And quite recently interest has been awakened in the possible pathogenic properties of certain of the fungi, among which it is suggested may be found the cause of other unexplainable diseases as cancer, smallpox, scarlet fever, measles, and rabi Several bacteria also not mentioned in this list hj created considerable discussion of late; but tl organisms have not yet been positively shown to be the specific cause of the diseases with which they are found associated, and hence have been omitted. General Characteristics op Bacteria. — Clax- sification and Definition. — Under the general term "microorganism" may be included all the minute lower forms of life which are of biological or hygienic interest, and which are the cause of fermentation putrefaction, and disease. They are both of the vegetable and of the animal kingdom; among the latter of these are the protozoa, and among the former the fungi and bacteria. Bacteria are classed among plants from the fact that they are able to derive their nourishment both from organic and inorganic mater- ials. They are of the class of cryptogamons plant*, that is, plants which, having no seeds or flowers, are reproduced by means of spores, such as the fungi, lichens, and algae. Of these they are most nearly allied to the alga?, but differ from them in that they are without chlorophyll, the green coloring matter by means of which the higher plants, under the influence of sunlight, decompose carbon dioxide, ammonia, and sulphurated hydrogen into their elementary con- stituents. In many respects bacteria resemble the mycetes or fungi, which are also without chlorophyll; but they differ from these again in their mode" of reproduction, being reproduced by division or simple fission. Hence bacteria have been called schizomycetes or fission fungi. A few varieties of unicellular organisms have also been found resembling bacteria in all points, except that they possess chloro- phyll or some pigment substance similar to it. Other organisms, again, have been observed which, though they are without chlorophyll, are able to build up organic compounds synthetically and even in the absence of light. Some bacteria, moreover, especially the motile forms, are closely allied to certain micro- organisms belonging to the animal kingdom. It is therefore difficult to classify or define bacteria scientifically, under our existing knowdedge of them. Excluding the microorganisms, however, which contain chlorophyll, bacteria may be defined ac- curately enough for all practical purposes as ex- tremely minute living vegetable organisms, without chlorophyll, which arc reproduced by division, con- sisting of single spherical, rod-shaped, or corkscrew- like cells or aggregation of such alls, between irliose protoplasm and nucleus it has not been possible to differentiate with certainty. Bacteria, then, belong to the family of mycetes or fungi, of which there are four groups: 1. Hyphomycetcs, or mould fungi. 2. Blastomyci U a, or yeast fungi. 3. Streptothrices. 4. Schizomycetes or bacteria. But besides this classification of bacteria it becomes necessary to divide them into saprophytes or refuse- eaters, and parasites. Saprophytic microorganisms are such as commonly exist independently of a living host, obtaining their supply of nutriment from soluble food stuffs in dead organic matter. Parasitic micro- organisms, on the contrary, live on or in some other living organism, from which they derive their nourish- ment for the whole or a part of their existence. Those microorganisms which depend entirely upon a living host for their existence are known as strict or REFERENCE HANDBOOK OF THi: MEDICAL SCIENCES Bacteria >bligatory parasites; those which can lead a saprophytic istence, bul also thrive within the body o animal, arc called facuttatir, . The sapro- phytes strictly so called, which represent the larger number of microorganisms, are not only harmli but perform the useful function of the destruction of dead organic matter through fermentation and putrefaction. The parasites, on the other hand, though Mime of them may multiply in the secretions or on the surface of the body without injury to the animal upon which they exist, are usually harmful iders, giving rise, through the lesions brought about in the body by their growth and products, to various acute and chronic infectious diseases. Numerous attempts have been made by various authors to classify bacteria systematically, but usually with the proviso that the system was only a temporary one. As a rule, the genera are based upon morphological characters and the species upon biochemical, physiological, or pathogenic properties. While the form, size, and method of division are the most permanent characteristics of microorganisms, and so are naturally utilized for classifications, nevertheless on this basis of arrangement there are ided difficulties. Thus while the form and size of bacteria are fairly constant under the same condi- tions, they are in many quite different under diverse conditions. Another serious drawback is that I morphological characteristics give no indication whatever of the relation of bacteria to disease, etc. — the very characteristics for which as physicians we study them. < Ither properties of bacteria which are fairly constant under uniform conditions are those of spore formation, motility, reaction to staining agent-, relation to temperature, to oxygen or other food materials, and finally their relation to disease, fermen- tation, and pigmentation (pathogenic, zymogenic, and chromogenic bacteria). Taking any one of these properties of bacteria as a basis, we can classify them; but even here there will be groups which under certain conditions would be placed in one class and under other conditions in another. Thus the power to produce spores 11133- be totally lost or held in abeyance for a time. The relation to oxy- gen may be gradually altered, so that an anaerobic species grows in the presence of oxygen. Parasitic bacteria ma3' be so cultivated as to become saprophy- tic varieties, and those which have no power to grow- in the living body given pathogenic properties. The possibility of making any thoroughly satisfactory clas- sification is rendered still more difficult by the fact that many necessarily imperfect attempts have already been made, so that there is a great deal of confusion, which is steadily increased as new varieties are found or old ones reinvestigated and classified differently in the various systems. We shall, therefore, simply use the commonly accepted nomenclature, without any attempt at classification, except to consider together as far as practicable certain groups of bacteria whose members are closely allied to one another in some one or more important features. Morphology. — There are three basic forms of the individual bacterial cells: the sphere, the rod, and the segment of a spiral. Although under different conditions the form of any one species may vary considerably, yet these three main divisions under similar conditions are permanent; and so far as we know, it is never possible by any means to bring about changes in the organisms that will result in the conversion of the morphology of the members of one group into that of another — that is, cocci always, under suitable conditions, produce cocci, bacilli pro- duce bacilli, and spirilla produce spirilla. The form of the bacterial cells at their stage of com- plete development must be distinguished from that which they possess just after or before they have divided. As the spherical cell develops preparatory to its division into two cells, it becomes elongated ami appears as a -hort oval rod at thi of its division; on the contrary, the tran verse diameter of each of its two halvi ater than their long di- ameter. A shorl rod becomes in the same way, al the "-tit of its divi 1 1 cells, the long diameter "i each of which may he even a trifle less than its shorl diameter, and thus they appear on superficial e lamination as spheres. As bacteria multiply the cells produced from the parent cell hai ea 1 ncy to remain at taihed. In some varieties this tendency is ex- tremely marked, in others it is slight. This union may appear simply as an aggregation of separate bacteria or so close that the group present- appearance of a single cell. According to the method ot the cell division and the tenacity with which cells h,,i ( i together we get different grouping bacteria, which aid us in their identification and differentiation. Thus whether the bacteria] cell divides in one, two, or three plane-, we get forms built in on.-, two, or three dimensions. If we gi bacteria according to the characteristic forms of the cells, and then subdivide according to the manner of their division in reproduction and the tenacity with which the newly developed cells cling to one another, we -hall have the following varieties: 1. Coccus or Micrococcus. — Spherical or sub- spherical forms. (a) Single coccus, grouped irregularly. (b) I ■ is, forming pairs. (c) Streptococcus, forming chains, often showing paired cocci. T< tracoccus, forming fours by division through two planes of space. ■ Sarcina, forming packets of eight by division through three planes of space. (J) Staphylococcus, forming irregularly shaped, grape-like bunches by division apparently in any axis. 2. Bacillus. — Oblong or cylindrical forms, having one dimension greater than any other, more or less straight, and never forming spirals, dividing only in one plane perpendicular to its long axis. (a) Single bacillus. (b) LHplobacillus and streptobacillus, forming twos or longer chains, the bacilli attached end to end. (c) Filaments or thread-like growths, in which division into bacilli of the normal length are not apparent, or occur irregularly and transversely to the long axis of the growth. 3. Spirillum. — Cylindrical and curved forms, con- stituting complete spirals or portions of spirals. Spirilla. like bacilli, divide only in one direction. A single cell, a pair, or the union of two or more elements may thus present the appearance of a short segment of a spiral or a comma-shaped form, an S-shaped form, or a complete spiral or corkscrew-like form. The term bacterium has also been used by some authors for bacilli or rod-shaped organisms; while to spirilla the terms vibrio and spirochcete have some- times been applied. But as there is no uniformity among bacteriologists as to the exact meaning of these terms, we shall employ only the terms bacillus and spirillum to denote these different groups. Structure of Bacterial Cells. — A bacterial cell con- -i-t- of protoplasm enveloped in a cell membrane; the cells as a rule being homogeneous and without visible nucleus. The cell is generally colorless, though in some species it contains chlorophyll or other similar coloring matter. The protoplasm may at times also contain minute granules of sulphur and 1 iccasionally refractive oily particles or colorless spaces in stained specimens, which have been mistaken for spores, but are supposed to be due to the shrinkage of the protoplasm with partial dissolution of the cell wall caused by abstraction of water, known as plasmolysis. In many species of bacteria, as in the diphtheria bacillus, there is observed in the interior 829 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of the cells on suitable staining, a peculiar granular appearance, to which has been given the names metachromatic bodies or sporogenous granules. The cell membrane is sometimes colored, and sometimes surrounded by a gelatinous envelope or capsule, which can be occasionally brought out by staining. The demonstration of this capsule may be of assist- ance in differentiating between certain bacteria, as, for example, some forms of the streptococcus and pneumococcus. A peculiarity of the capsule bacteria is that, except very rarely, they exhibit this envelope only when grown in the animal body or in special culture media, such as liquid blood serum, bronchial mucus, etc. The outer surface of bacteria when occurring in the form of spheres and short rods is almost always smooth and devoid of appendages; but the larger rods and spirals are usually provided with fine hair-like cilia or flagella, which are their organs of motility. These flagella, either singly or in numbers, are sometimes distributed over the entire body of the cell, or they may form a tuft at one end of the rod, or only one polar flageltum is found. The polar flagella appear in the cells shortly before division. They are believed to be formed of proto- plasmic material, which penetrates the cell mem- brane, and probably to have the property of pro- trusion and retraction; but their nature is imperfectly understood. So far as we know, the flagella are the only means of locomotion of bacteria. They are not readily stained, special mordants being required for this purpose. Bacteria may lose their power of producing flagella for several generations, whether permanently or not is not known. Vegetative Reproduction. — The process of vegetative reproduction of bacteria, which is to be distinguished from spore formation, takes place by division, and may go on, under favorable conditions, indefinitely. When development is in progress a single cell will be seen to elongate in one direction. Over the center of the long axis thus formed there appears a slight indentation in the outer envelope of the cell; this indentation increases until there exist two distinct cells. As a rule, the cells separate soon after division, but occasionally they remain together for a time, forming pairs and chains, or under certain conditions of nutrition long threads or filaments which break up into fragments, however, when placed under other conditions. Although elongation in one direc- tion and transverse division is the rule for most bacteria, there are certain groups (as the sarcina, for example) which divide more or less regularly in three directions. Division in two directions results, as already mentioned, in the formation of tetrads; while division irregularly in all directions produces grape-like clusters. Bacilli and spirilla, as far as we know, never divide longitudinally. Spore Formation. — This is the process by which bacteria are enabled to enter a stage in which they resist deleterious influences to a much higher degree than is possible for them in the growing or vegetative condition. It is not a process of multiplication of bacteria, but only one of reproduction for the preser- vation of the species under conditions unfavorable to their growth, and occurs when the organism has nearly exhausted its supply of nutrition or poisoned it with products of its growth, etc. The fungi, on the other hand, form spores under the most favorable conditions, even requiring an abundant supply of nutrition for their production, the life history of the fungi, indeed, being incomplete without the formation of spores. But in bacteria the process is compara- tively rare, and all the conditions which tend to bring it about are not yet known. Two kinds of spores have been described in bacteria: 1. Endospores, which are strongly refractile and glistening in appearance, oval or round in shape, and developed within the interior of the cell. They 830 are characterized by the power of resisting to a considerable extent the injurious influences of heat, desiccation, and chemical disinfectants, which would kill vegetative cells. 2. Artitrospores or jointed spores, developed, not within the cell, but as a sprout- like projection from one of its extremities. These jointed bodies are believed by Hueppe to have also more or less power of resistance to desiccation, etc., than the ordinary cells, though less than endospori but they have been but little studied, and their exist- ence in bacteria is still an open question. In describ- ing the biological characters, therefore, of the varioi species, whenever their property of spore formation is mentioned it will be understood that endogenous spores are meant. The production of endospores in the different bacterial species, though not identical, is very similar. Spores represent a state of suspended activity, and motile organisms always come to a state of rest or immobility previous to spore formation. The fol- lowing description of the method of spore form i- tion in the anthrax bacillus may serve as an illustra- tion of the process: Under suitable conditions of temperature, moisture, etc., the cell is elongated and at first the protoplasm is clear and homogeneous, but after a time it becomes turbid and finely granular. These fine granules are then replaced by a smaller number of coarser granules, which are finally amal- gamated into a spherical or ovoid refractile body. This is the spore. As soon as the process is completed there appears between two spores a delicate partition wall. For a time the spores are retained in a linear position by the cell membrane of the rod, but this later is dissolved or disintegrated and the spores are set free. The following types have been observed: (n) Spores lying in the interior of a short, undistended cell; (b) spores lying in the interior of a short, undistended cell, forming one of the elements of a long filament; (c) the spores lying at the extremity of an undistended cell much enlarged at that end — the so-called "head spores"; and (d) the spores lying in the interior of a much enlarged cell in its central portion, giving it a spindle shape. The germination of spores takes place as follows: By the absorption of water the spores become swollen and paler in color, losing their shining, refractile appearance. Later a little protuberance is seen to project from one side or at the extremity of the spore; this rapidly grows out to form a new rod, which consists of soft protoplasm enclosed in a membrane formed of the inner layer of the cellular envelope, or endosporum. The outer envelope, or exosporum, is then cast off, and may often be seen in the vicinity of the newly formed rod. In some species the vegetative cell emerges from one end of the oval spore, and in other species the exosporum is ruptured and the bacillus emerges from the side. Involution Foryns. — In old cultures of bacteria in which deleterious substances have been produced or the supply of nutriment has been exhausted, there air frequently found irregular or distorted forms, which are thought to be due to abnormal development of the bacterial cells under unfavorable conditions. These are generally spoken of as involution or degenerated forms, though sometimes the terms pleomorphism and polymorphism are applied to them. Placed under suitable conditions these irregular or deformed cells again produce normally shaped organisms. Chemical Composition. — Qualitatively considered, bacterial cells consist of carbon, hydrogen, oxygen, and nitrogen, for the most part in the form of water, salts, fats, and albuminous substances. There are also present, in smaller quantities, extractive sub- stances soluble in alcohol. Glucose has not been found in any bacteria, but many species contain starchy substances which give a reaction with iodine. REl'ERKXCi: IIANDHooK uF Till'. MI'.llK'AI, Si II WES Bacteria Cellulose has also been detected in certain species, as i he Bacillus subtilis, some of the colon group, and the tubercle bacillus. The nuclein bases, xanthin, guanin, ami adenin, moreover, have been found in considerable amounts. There is also a group of bac- teria, l lie Bcggiatoa, which contain sulphur, and another group, the Cladothrix, has the power of sepa- rating ferric oxide from water containing iron, as in iron and sulphur springs. Hut very little is known about the chemical composition of bacteria quanti- tatively, only a few species having been completely analyzed; but the percentage composition would appear to depend largely upon the character and constituents of the culture media in which they are grown. Conditions of Growth. — Although there are some pathogenic bacteria which grow only in I In' bodies of Uving animals and plants, and are therefore apparently strict parasites, yet the majority of pathogenic micro- organisms can be cultivated more or less readily in artificial culture media, and are thus facultative parasites. The saprophytic bacteria, as a rule, are easily cultivated artificially, though some of these, as certain organisms met with in the saliva and in water, are very difficult or impossible to cultivate. The essential condition for the cultivation of all bacteria is water; salts are also indispensable, and organic matter for the supply of carbon and nitrogen. Most of the important bacteria and all the pathogenic species thrive best in media containing albumin and of a neutral or slightly alkaline reaction. The de- mands of bacteria, however, with regard to nutrition are various. Some water bacteria, for instance, require so little organic food that they will grow in water that has been twice distilled, and in which no nutritive material can be chemically demonstrated. But the pathogenic bacteria are seldom so easily satisfied, though there are several species which will develop in comparatively simple culture media and without albumin. Considering more in detail the source of the im- portant chemical ingredients of bacteria, we find that their nitrogen is most readily obtained from diffusible albuminous material and less easily from ammonium compounds. Their carbon they derive from carbo- hydrates, albumin, peptone, sugars, glycerin, fats, and other organic substances. Some bacteria grow- best in special culture media, such as bouillon, gelatin, agar, blood serum, potato, milk, etc. The majority of bacteria absolutely require the presence of free oxygen for their growth, although a consider- able number fail to develop at all unless oxygen is excluded. Between these two groups of aerobic and anaerobic bacteria, we have those which grow either with or without oxygen. Some of the strictly anaerobic species require for their full development the presence of fermentible substances, such as sugars, from which they obtain their oxygen. In so far as the amount of oxygen present acts un- favorably upon bacteria, there will be more or less restriction in certain of their life processes, such as pigment and toxin production, spore formation, etc. Some aerobic bacteria, however, can be accustomed to grow without oxygen, while certain of the anae- robes can be gradually made to develop in its presence. Among other food stuffs required by bacteria are sulphur and phosphorus; calcium or magnesium and sodium or potassium are also usually needed. Very few species require iron. With regard to the more complex culture media, whether naturally existing, such as blood serum, ascitic fluid, etc., or artificially made, as bouillon, glycerin, and agar, beyond the necessary amount of soluble nutrition present, the points of greatest im- portance are the relative proportion of each form of food and its total concentration. Very wide differ- ences, however, may exist in the composition of the culture media with but slight effect upon ihe develop- ment of bacteria, the growth usually ceasing on ac- counl of (he accumulation of deleterious substat in the media rather than from exhaustion ol the food supply. 'Ihe reaction of culture media is of great importance. Most bacteria grow besl in neutral or -lightly alkaline media, very few requiring an acid medium, and Done of the parasitic species. \n amount of acid <, r alkali insufficient to prevenl the development of bacteria may yet suffice to rob them of some of their mo I important functions, as the production of toxins. The influence of one species of bacteria upon the growth of another, either w hen cultivated together or following one another, is very noticeable. The develop- ment of one species of bacteria in a medium causes that substance usually to become less suitable for the growth of other bacteria. This is due partly to the impoverishment of the medium, but also to 'the pro- duction of chemical substances or enzymes which are antagonistic not only to the growth of the bacteria producing them, but to many other species; very rarely are the changes produced by one species of bacteria in the media favorable to some other specie-. A suitable temperature is also essential for the growth of bacteria. The most favorable or optimum temperature varies for different species, but for any bacteria a range of about 2.5° C. above or below the optimum covers the limits of their most vigorous growth. Few bacteria grow well under 10° C. or over lit C; 2° C. is about the lowest temperature at which bacterial species has been known to grow, and 70° C. is the highest. In many cases the temperature of the natural medium in which the bacteria have been deposited is the controlling factor in deciding the temperature at which they will or will not grow under artificial conditions. Thus nearly all parasitic bacteria require a temperature near that of the body (36° -38° V.) for their development, while many saprophytic bacteria can grow only at much lower temperature. Bacteria exposed to lower temper- ature than suffices for their growth, while having their activity inhibited, are not otherwise injured; but exposure to a higher temperature than that which permits growth destroys the life of bacteria. Vital Phenomena of Bacteria. — Motility. — .Many bacteria when examined in the hanging drop are seen to exhibit active movements. This motility is produced by the fine hair-like flagella attached to all motile species. The movements are various — creeping, rotary, undulatory, etc., at one time being slow and sluggish and at another so rapid that no detailed observation is possible. The spontaneous movements of bacteria are to be distinguished from the so-called Browtuan or molecular movement, which is a dancing, trembling, stationary motion possessed by all finely divided organic particles. Not all species of bacteria, however, which have flagella exhibit spontaneous motility invariably; in certain culture media and at too low or too high temperatures, and when there is an insufficient or excessive supply of oxygen, motility may be absent. The property of motility, therefore, evidently depends upon other factors than flagella. Some chemical substances apparently exert a peculiar attraction for bacteria, known as positive chemotaxis, while others repel them, negative chemotaxis; not all varieties, however, are affected alike, for the same substances may exert on some bacteria an attraction and on others a repulsion. Oxygen, for example, attracts aerobic and repels anaerobic species, and for each different species there is a definite amount of oxygen which most strongly attracts or repels. Possibly these chemotactic properties, which are as yet but little understood, may, under certain conditions, have something to do with the motility of bacteria, 831 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES independently of their organs of locomotion, the flagella. Production of Light. — Some bacteria have the prop- erty of emitting light; these are quite widely dis- tributed in nature, particularly in sea water, salt fish, etc. The emission of light or phosphorescence is a property of the living protoplasm of bacteria, and is not usually due to the oxidation of any photogenic substance produced by them. Anything which is injurious to the life of the organism affects this prop- erty, as too cold or too high a temperature, chloro- form, etc. But while the organism is unable to emit light except during life, it can live, as in an atmos- phere of CO.,, without exerting this property. The power of phosphorescence is soon lost, unless the organism is constantly transplanted to fresh media, the presence of oxygen, carbon, and nitrogen being usually required to preserve the property. Thermic Effects. — Most bacteria possess the power of producing heat, although this does not ordinarily attract attention because of the slight amount of heat produced in cultures. Careful tests, however, have shown that heat is produced. The increase of temperature in organic substances when stored in a moist condition, as tobacco, hay, manure, etc., is partly, at least, due to the action of bacteria. The high temperature thus exhibited may be caused, as Rabinowitsch suggests, by the so-called thermo- philic bacteria. Chemical Effects. — The processes which substances undergo in being decomposed depend, first, on the chemical composition of the substances involved and the conditions under which they exist, and, secondly, on the action of bacteria present. Bacteria are able to construct their body substance out of various kinds of nutritive materials and also to produce fermentative products and poisons, and they can do these things either analytically or synthetically with al- most equal facility. In the chemical building up of their cell substance we may distinguish several groups of phenomena: polymerization, a sort of doubling up of a simple compound; synthesis, a union of different kinds of simple substances into one or more complex compounds; formation of anhydrides, by which new substances arise from a compound through loss of water; and reduction or loss of oxygen, which is brought about especially by the entrance of hydrogen into the molecule. The breaking down of organic bodies of complicated molecular structure into sim- pler combinations takes place, on the other hand, through the loosening of the bands of polymerization, by hydration or entrance of water into the molecule, or by oxidation. The chemical effects of bacteria are greatly in- fluenced by the presence or absence of free oxygen. The access of pure atmospheric oxygen makes the life process of most bacteria more easy, but it is not indispensable when available substances are present which can be broken up with sufficient ease. Life processes carried on without oxygen do not effect any profound molecular changes in the organic material which is decomposed; but in order that the living organism may obtain the requisite amount of energy from this mode of life, a proportionately large quan- tity of material must be decomposed. Therein lies the power of a small amount of ferment to produce much alcohol or lactic acid, and of parasites which have invaded the living body to generate intensely poisonous substances out of the body proteids. In the presence of oxygen the decomposition products formed by the action of anaerobic bacteria are further decomposed and oxidized by the aerobes, being thus rendered inert, as a rule, and consequently harmless. Some bacteria have adapted themselves to the use of oxygen compounds, from which they are able to obtain their oxygen; and others — the obligatory or strict aerobes — are able to live only in the presence of oxygen. The facts of anaerobiosis are of great importance to technical biology and path- ology. Under strictly anaerobic conditions, second- ary oxidation of the products of decomposition being impossible, the latter accumulate without the forma- tion of by-products. Thus parasitic bacteria are often found to produce far more poison in the ab>i than in the presence of air. Fermentation; the Production of Organized and Unorganized Ferments. — The chemical effects of bacteria are largely dependent upon the composition of the culture media. Thus many species which in albuminous media produce no visible changes, when sugar is added give rise to fermentation with the formation of gas. The term fermentation is differently applied by different authors. Some call even kind of decomposition due to bacteria a fermentation; others limit the term to the process when accompanied by the visible production of gas; while others again take fermentation to mean only the decomposition of carbohydrates, with or without gas production. Fer- mentation may be properly defined as a chemical decomposition of an organic compound, induced by living organisms or substances contained within them (organized ferments), or by chemical substances thrown off from the bacteria (unorganized ferment-i. In the first the action is due to the growth of tin: organisms producing the ferments, as in the formation of acetic acid from alcohol by the action of the vinegar plant, and in the second the enzyme causes a structural change without losing its identity, as in digestion. These ferments or enzymes, even when present in the most minute quantities, have the power of splitting up or decomposing complex organic com- pounds into simpler, more easily soluble or diffus- ible molecules. Ferments, like albuminoids, are not dialyzable. They withstand dry heat, but are de- stroyed in watery solution by a temperature of over 70° C. They are injured by acids, especially mineral acids, but are resistant to alkalies. All fermentation has for its object the acquisition by the organism of a store of energy. This storing up of energy is acquired in either of the ways above mentioned. The common- est example of fermentation by decomposition is that of sugar into alcohol and carbonic acid. Exactly opposite to this, and far less common, is fermentation by oxidation, as in the production of acetic acid from alcohol. Proteolytic or peptonizing ferments, which are similar to pepsin and trypsin, in that they decom- pose insoluble albuminoids into soluble or digestible substances, are very widely distributed. The lique- faction of gelatin, produced by many species of bacte- ria, is due to the presence of these peptonizing fer- ments. Diastatic ferments, which convert starch into sugar, like ptyalin, are also produced by bacteria. Other bacterial ferments are the invertive ferments, or those which convert cane sugar into grape sugar; and the rennet ferments having the power of coagulat- ing milk. The process of fermentation also gives rise to prod- ucts that are destructive to the ferments; hence fermentation ceases when the nutriment is exhausted. Different kinds of fermentation are called by different names according to the products they yield. Thus, aeetic acid fermentation, alcoholic or vinous fermenta- tion, lactic acid fermentation, butyric acid fermenta- tion, etc., are produced by different species of bacteria. Putrefaction. — By putrefaction in the common acceptation of the term is understood the decomposi- tion of animal or vegetable matter, accompanied by the generation of fetid odors. Scientifically con- sidered it is a kind of fermentation or the decomposi- tion of complex organic compounds, albuminous substances and the like, into simpler combinations, produced by microorganisms called putrefactive ferments. Typical putrefaction occurs only when oxygen is absent or scanty. As putrefactive products we have peptone, ammonia, and the amines — leucin, 832 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria tyrosin, and other amido-substances; oxyfatty acids, indol, scatol, phenol; and finally sulphureted hydro gen, mercaptan, carbon dioxide, hydrogen, and possibly marsh gas. ,1,1 Production. — Various bacteria form characteristic pigments as products of their growth, S ime of these have been isolated and have been round to possess many of the properties of the aniline dyes. fhey have no known importance in connection with ase, bii t are of interest and value in identifying certain species of bacteria. The principal pigments need by chromogenic bacteria which have been ideally studied are: red, yellow, violet, bine, and in pigments. All conditions which are unfavorable he growth of the bacteria decrease their power oi pigment production, as cultivation in unsuitable media or too low or too high a temperature, etc. Alkaline Products and the Decomposition of Urea. — ibic bacteria sometimes produce alkaline products albuminous substances in culture media free from sugar. Most species produce acids in the pres- ceoi sugar, neutral or slightly alkaline cultures thus often becoming acid at first, owing to the small quantity of sugar contained in the meat used for making nutrient media; and later when the sugar is ( \luiusted they become alkaline again. The sub- stances producing the alkalinity of cultures are chiefly ammonia, the amines, and the ammonium salts. The conversion of urea into carbonate of ammonia is due to the action of bacteria. Several organisms also have been isolated which separate ammonia from Ptomaines. — Brieger has recognized a number of complex alkaloids, closely resembling those found in ordinary plants, which are the products of bacterial growth; and these alkaloids he has named ptomaines (from TTTUfia, a cadaver), because obtained from putrefying or dead bodies. Nencke, and later Brieger, Vaughan, and others, have succeeded in preparing organic bases of definite chemical compo- sition out of putrefying fluids — meat, fish, old cheese, milk, etc., as well as from pure cultures of bacteria. Some of these were found to exert a poisonous effect, and for a long time were looked upon as the specific bacterial poison, while others were harmless. The nis are particularly interesting, as they may be present in the putrefying cadaver, and hence must be taken into consideration in medicolegal questions. They may also be formed in the living body, and if not rendered innocuous by oxidation may come to act therein as self-poisons or leucomaines. Recent investigations have shown that these are not the sub- stances to which are due the specific toxic effects of bacteria, which are designated toxins and have quite different characteristics. The best-known ptomaines are: CoUidine from putrefying meat or gelatin, cadaverine from decom- posing dead bodies, neurine, and muscarine. The first two of these contain no oxygen, and are non-poisonous, while the last two ptomaines contain oxygen and have a poisonous action the opposite of atropine. Tyro- toxicon, a ptomaine decomposing milk, and found by Vaughan in poisonous cheese, is apparently derived from butyric acid. Pyocyanine, which produces the color of blue and green pus, is a ptomaine pigment. Similar bodies may also be found in the intestinal contents as products of bacterial decomposition. Some of them are poisonous and can be absorbed into the body, where they play the part of self- poisons or leucomaines; and it has been thought that the symptoms designated as coma and tetany may be ascribed to the absorption of substances of this nature. The name ptomaine was formerly, and is still by some authors, applied to all bacterial poisons, as in cases of so-called food poisoning due to de- composing meat, sausage, cheese, or milk. But in- stead of ptomaines, which are now commonly under- stood to include only the crystalline products of Vol. I.— 53 bacterial grow ths, these effects maj be cau ed to the p"i onon protein or toxins, which an formed in the beginning of putrefactive proce • . Some of the ptomaines obtained bj cl I an not due to put refact ive cha ngi at all, but to i he chemical on i boas employed in separat ing them. Toxins. — Any poisonous sub tance formed in growth of bacteria or other microorganism ma be called a toxin. The different bacterial toxins vary greatly in their characteristics. As little is km concerning their chemical nature, thej cannot be definitely classified. But for practical porposes they may lie divided into two group-: i. Extracellular toxins — specific toxic producl , soluble in water, which are excreted by \ ai iet bactei ia in ordi nary culture media. Type diphtheria, tetanus. 2. Intraculhdar toxins or endotoxin true toxins, which are more or less closely bound to the living cell, and which are only in a small degree separable in un- changed condition outside of the body. Type — cholera, typhoid, pneumococcus. Among the intra- cellular toxins some which are resistant to heat are somet imes called prott Of the properties of the extracellular toxins the following are the most important: They are, so far as known, uncrystallizable, and thus differ from pto- maine-; they are soluble in water ami they are slowly dialyzable through thin but not through thick mem- branes; they arc precipitated along with proteins by concentrated alcohol, sixty-live per cent, or over, and also by ammonium sulphate; if they are proteins they are either albumoses or allied to the albumoses; they are relatively unstable, Inning their toxicity dimin- ished or destroyed by heat as well as by chemial manipulation. Their potency is often altered in the precipitation practised to obtain them in a pure or concentrated condition, but among the precipitants ammonium sulphate has but moderately harmful effect. They are highly specific in their properties and have the power in the infected body to excite the production of antitoxins — which is their most remarkable characteristic. Regarding the properties of the intracellular toxins much less is known, but it is probable that their chemical nature is somewhat similar, though they differ in their resistance to heat. For instance, some of the toxins elaborated by tubercle bacilli withstand boiling, while others do not. In the case of all toxins, the fatal dose for an animal varies with the body weight, age, and general conditions. The most important of the extracellular toxins are those produced by the diphtheria and tetanus bacilli. The toxicity of the purest tetanus toxin now obtain- able is almost incredible and is perhaps the most powerful poison known; 0.0005 mgm. of it kills a mouse of 15 gm. weight; hence a man of 150 pounds weight, if he were equally susceptible, would be killed with 0.23 mgm. In order to appreciate the activity of this toxin, we have only to consider that it requires a dose of from 30 to 100 mgm. of strychnine to kill a man under ordinary circumstances. Similar Vegetable and Animal Poisons. — Substances similar to the bacterial endotoxins and soluble toxins are formed by many varieties of cells other than bacteria. The ricin and abrin poisons obtained from the seeds of Ricinus communis and Abrus precatorius have a number of properties similar to those of diph- theria and tetanus. Such substances have been called toxalbumins. Poisonous snakes also secrete a venom having many of the characteristics of the bacterial albumoses. Reduction Processes. — All bacteria possess the prop- erty of converting sulphur into H 2 S in the pres- ence of nascent hydrogen. This is a very common bacterial product. It may be formed: (1) From albuminous substances; (2) from powdered sulphur; (3) from thiosulphates and sulphites. The presence of sugar in the culture media does not effect the S33 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES production of H 2 S, but saltpetre reduces it, with the formation of nitrites. The following reduction processes brought about by bacteria also depend in part upon the action of nascent hydrogen: The reduction of blue litmus pigments, methylene blue and indigo to colorless substances; the reduction of nitrates to nitrites and ammonia, and even to free nitrogen. The so-called "cholera-red reaction" de- pends upon the reduction of nitrates to nitrites by the cholera spirillum together with the production of indol. When chemically pure nitric or sulphuric acid is added to nutrient peptone cultures of the cholera spirillum a rose-red or violet color is produced. The mineral acid splits up the nitrites present, setting free nitrous acid which, with the indol, gives the red reaction. Although called " cholera red, this nitroso- indol reaction is not confined to the cholera spiril- lum, but may be applied to many other bacteria. Out of sixty species examined by Lehmann, twenty- three gave the indol reaction; but the test is of practi- cal value in differentiating the cholera spirillum from several other similar species for which it may be mistaken. Denitrification. — This process is brought about by a number of bacteria which separate nitrogen from the nitrates and nitrites. The practical significance of these organisms, the denitrifying bacteria, is that by their action large quantities of nitrates in the soil and in manure, which are necessary for plant food, may thus become lost through conversion into free nitrogen. Assimilation of Nitrogen. — Although so far as we know none of the higher plants have the power of assimilating nitrogen from the atmosphere, this property is possessed by at least one species of bacteria, the Bacillus radicicola of Beyerinck. This organism is found in the root nodules of various leguminous plants (peas, clover, lupine, etc.), and can be isolated from these. Different varieties of this bacillus exist in different kinds of legumes, each legume apparently having a special variety adapted to its needs. There are also certain neutral varieties, however, existing free in the soil. By the aid of these root bacteria, leguminous plants are enabled to assimilate nitrogen from the atmosphere, thus en- riching sandy soils which are naturally poor in nitro- gen, so that- they yield good harvests. Formation of Acids from Carbohydrates. — Many bac- teria form free acids in culture media containing carbohydrates (sugar). Acid formation occurs some- times with and sometimes without the production of gas. Excessive formation of acid may cause the death of the bacteria from the increased acidity of the media in which they are cultivated. All anaerobic and facultative anaerobic species form acids from sugar; the strictly aerobic species do not, or they do it so slowly that the acid is hidden by the almost simultaneous production of alkali (Theo- bold Smith). If after the sugar is used up not enough acid has been formed to kill the bacteria, the medium becomes again neutralized and finally alkaline. Among the acids produced the most important is lactic acid, also traces of formic, acetic, propionic, and butyric acids, and not infrequently ethyl alcohol and aldehyde. Gas Formation. — The only gas produced by bacteria in visible quantity in culture media free from sugar is nitrogen. In the presence of sugar, so long as lactic or acetic acid is produced, there may be no gas production; but frequently gas may be abundantly formed, especially by anaerobic bacteria or in the absence of air. About one-third of the acid-producing species also develop gas, consisting chiefly of carbon dioxide and hydrogen. Bacteria which decompose cellulose also produce marsh gas. Acid Production from Alcohol. — It has long been known that the conversion of ethyl alcohol into acetic acid is due to the action of bacteria. The conversion of the higher alcohols — glycerin, mannit etc. — into acids is also caused by bacterial action' as is also the conversion of the fatty acids and their salts into other acids, as for instance the salts of lactic, malic, tartaric, and citric acids into butyric propionic, valerianic, acetic acids, etc. Effects of Outside Influences upon Bacteria. — Very little is known about the influence of electricity on bacteria; but the observations heretofore made on this subject would seem to indicate that there is no direct action of the galvanic current on microorgan- isms, though the effect of heat and electrolysis may produce changes in the culture which finally sterilize it Slight agitation of cultures of bacteria seems to act favorably on their development, but protracted and violent shaking destroys the vitality of bacteria by causing a molecular disintegration of their cells. Pressure exerts comparatively little influence on bacteria. A culture of the bacillus pyocyaneus subjected to a pressure of fifty atmospheres unde C0 2 still grew at the end of four hours, but the power of pigment production was lost. After six hours' exposure to this pressure a few colonies still developed, but after twenty-four hours no growth occurred. Light. — A large number, perhaps the majority, of bacteria are inhibited in growth by the action of diffuse daylight, still more by that of direct sunlight. Dieudonne found that the bacillus prodigiosus exposed to the action of direct sunlight during the months of March, July, and August were killed in an hour and a half; during the month of November, in two and a half hours. Diffuse daylight in March and July inhibited development after three and a half hours' exposure; in November after four and a half hours, and vitality was completely destroyed in from five to six hours. Exposure to the action of the electric arc light inhibited development in five hours and destroyed vitality in eight hours; incan- descent light inhibited growth in from seven to eight hours and killed in eleven hours. Similar results have been obtained with other bacteria, as the Bacillus coli communis, Bacillus typhosus, and Bacillus anthracis. The tubercle bacillus was found by Koch to be killed by the action of direct sunlight in from five minutes to several hou*s, depending upon the thickness of the layer exposed and the season of the year. Diffuse daylight had the same effect in from five to seven days. It has been shown that it is only the ultra violet, violet, and blue rays of the solar spectrum which possess marked bactericidal action; the green rays very much less, and the red and yellow rays not at all. The action of light is apparently aided in most cases by the admission of air; but anaerobic bacteria, like the tetanus bacillus, and facultative anaerobic species, as the colon bacillus, are able to withstand the action of sunlight quite as well in the absence as in the presence of oxygen. The mechanism of the action of light has been partially explained, at least, by the demonstration of the formation of hydro- gen peroxide in cultures exposed to light for a short time. Influence of One Species of Bacteria upon Another. — If we examine water, milk, or the contents of the intestinal canal of either sick or healthy persons, we invariably find several species of bacteria occurring together. This association may at first seem to be purely accidental; but on further investigation it will be found that there are among bacteria synergists and antagonists, or at least certain species which apparently assist or oppose one another mutually or one-sidedly. This action is sometimes spoken of as symbiosis and enantobiosis (Nencke). Thus it has been found that many species of bacteria will not 834 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria row at all or only scantily in cultures when m close roximity to other species, the action Lent; mutual ,• one-sided. The practical application of tins tact in making plates for the isolation of pure cultures r for the counting of colonies, to have the plates as liin as possible. Bacteria may also oppose one , u ,ther antagonistically in the animal body. Km- lerich has shown that animals infected with anthrax ,-iy often be cured by a secondary infection with the treDtococcus. The symbiotic or cooperative action , Bacteria is of still greater importance Some ,-u-teria thrive better in association with other necies than alone. Certain anaerobic species for mce as the tetanus bacillus, grow even in the iresence of air, if associated with aerobic species. \eain certain chemical effects of bacteria, as denitn- icatio'n of nitrates, can be produced only when two ics are associated. In like manner it has been ,Wrved that some soil bacteria, though non-patho- ic in pure culture, when inoculated into animal- in combination with other species may produce disease. ,lly, slightly pathogenic species gain in virulence alien cultivated with common saprophytic bacteria, as the attenuated tetanus bacillus with Proteus vulgaris. Lack of Food and Desiccation.— Most bacteria, and especially the pathogenic species, which require much .rganic nutriment for their development, when placed in distilled water soon die; and even in ster- ilized water they live from eight to ten days only and rarely multiply. Desiccation affects bacteria in various ways. In dry culture media development soon ceases, although in media dried gradually at the same temperature bacteria may retain their vitality often for several months even in the absence of spores. Also under natural conditions, when these are favorable, many non-spore-bearing bacteria live a long time when exposed to desiccation, bpore- bearing species, however, are much more resistant to desiccation as also to other injurious outside influences such as heat, light, chemicals, etc. Behavior toward Oxygen and Other Gases.— As already noted it is customary to divide bacteria into three classes according to their behavior toward oxygen: aerobic, anaerobic, and facultative aerobic and anaerobic species. Aerobic bacteria grow only in the presence of oxvgen; the slightest restriction of air inhibits their development, spore formation especially requiring the free admission of air. Anaerobic bacteria grow and form spores only in the total exclusion of oxvgen. Among this class of organ- isms are many soil bacteria, such as the bacillus of malignant edema, the tetanus bacillus, and the bacillus of symptomatic anthrax. Exposed to the action of oxvgen, the vegetative forms of these bacteria are readily destroyed; their spores, however, are very resistant. Anaerobic bacteria being deprived of the oxygen of the air, are dependent for their nutriment upon decomposable substances such as glucose. Hence for their cultivation they require, as a rule, media containing from one to two per cent, of glucose or some other equivalent. Facultative Aerobic and Anaerobic Bacteria. — The greater number of aerobic bacteria, including most of the pathogenic species, are capable of withstanding, without being seriously affected, a considerable restriction of oxygen, and many grow equally well in the partial exclusion of this gas. Life in the animal body, for instance, necessitates an existence with a diminished supply of oxygen. Pigment production usually ceases with the exclusion of oxygen, but toxins are more abundantly formed. The presence of living or dead aerobic species may facilitate the aerobic growth of anaerobic species. Moreover, certain species which in their isolation at first show more or less anaerobic development, have been observed after a time to become aerobes, growing only on the surface of media. The fact, therefore, of an organism showing aerobic 01 anaerobic growth is nol suffii ienl to make oi i) a distim I Although all facultative as well a- obligati anaerobes grow luxuriantly in nitrogen or hydrogen gas, the same is not true of carbon dioxide gas. Ma species do not grow at all but are inhibited or killed bj rti , while others exhibit only a scanty growth, and very few are not affected. Sulphureted hydro- gen in large quantity is a strong bacterial poison, and in small amount even it destroys some pi i ie - Effect of Temperature.- Every bacterial species makes certain demands on temperature foi it - growth. Vegetative life is possible within the limits of 0° and 70° C; but there are some species of bacteria which grow at the lower and others at the upper limit ol this range. The maximum and minimum tempera- ture- for each species lie about 30° C. apart. Bacteria have thus been classified, according to the tempera- ture at which they develop, into: (1) Psychrophilic bacteria. .Minimum growth at 0° C, optimum at 15° to 20° C, maximum at about 30° C. To this class belong the water bacteria having the power of emitting light. (2) Mesophilic bacteria. Mini- mum growth at 10° to 15° C, optimum at 37° C., maximum at about 45° C. These include all the pathogenic species, the conditions for their growth in the animal body requiring acclimatization to the body temperature. (3) Thermophilic bacteria. Mini- mum growth at 40° to 49° C, optimum at 50° to 55° C, maximum at 60° to 70° C. This class includes many soil bacteria and almost exclusively spore-bear- ing species. They are found widely distributed in feces. By carefully elevating or reducing the temperature it is possible to extend the limits within which different species of bacteria will grow. Thus the anthrax bacillus has been made gradually to accommodate itself to a temperature of 42° C, and pigeons, which are comparatively immune to anthrax infection, on account of their high body temperature, wdren inoculated with this modified organism succumb to the disease. In the same way the anthrax bacillus has been acclimated to a temperature of 12° C, so that it killed frogs kept at this temperature (Dieu- donne) A. very virulent diphtheria bacillus has been so cultivated that it grew at 43° C. and produced strong toxin (Park). Bacterial growth, though retarded by temperatures just below the minimum of the species, is not other- wise injured. Cultures of bacteria which readily die fas the streptococcus) are often preserved in labora- tories by keeping them in the refrigerator at 4 to 6° C Temperatures even far below 0° C. are only slowly injurious to bacteria, different species being affected with varying rapidity. Ordinarily, low- temperatures, though arresting the growth, do not destroy the vitality of bacteria. Microorganisms have been exposed for hours in a freezing mixture at-lS° C and have been kept in an open tube in liquid air at- 175° C. for two hours, and yet have been found to grow when placed again under favorable conditions. Temperatures from 5° to 10° C. over the optimum, however, affect bacteria injuriously in several ways. The effects produced are the production of varieties of diminished activity of growth, weakening of virulence and decrease of the property of causing fermentation, and finally gradual loss of power of spore formation. One or other of these effects may predominate under varying conditions. If the maximum temperature is exceeded the organism soon dies; the thermal death point for psychrophilic species being about 37° C, for meso- philic about 45° to 55° C, and for thermophilic about 75° C. There are no non-spore-bearing bacteria S35 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES which, when moist, are able to withstand a tempera- ture of 100° C. even for a few minutes. According to Sternberg, ten minutes' exposure to moist heat "will kill the cholera spirillum at -52° C, the strepto- coccus at 54° C, the typhoid bacillus at 50° C, the diphtheria bacillus and gonococcus at 60° C, and the staphylococcus at 62° C., the last mentioned being the most resistant of pathogenic organisms without spores. When bacteria in a desiccated condition are exposed to the action of heated air the temperature required for their destruction is much above that needed when they are moist or exposed to the action of hot water or steam. A large number of bacteria are able to resist dry heat at a temperature of over 100° C. for an hour. A temperature of 120° to 130° C. maintained for an hour and a half is required to destroy all bacteria, in the absence of spores, if hot air is used. Spores are far more resistant to all injurious in- fluences than vegetative forms, and can withstand also a greater degree of both moist and dry heat. .Many spores are able to resist a temperature of 130° C. dry heat, the spores of the anthrax and the hay bacilli requiring, for instance, an exposure of three hours to a temperature of 140° C. to insure their destruction. Moist heat at a temperature of 100° C, either boiling water or streaming steam, destroys the spores of all known pathogenic bacteria within ten minutes; the spores of some non-pathogenic species resist this temperature, however, for hours. While steam under pressure is more effective than streaming steam in practical disinfection, it is scarcely necessary to give it the preference, inasmuch as all known pathogenic bacteria and their spores are quickly destroyed by the temperature of boiling water. "Superheated" steam has about the same germicidal power as hot, dry air at the same tem- perature, and is less effective, of course, than moist steam. Tyndalization; Fractional Sterilization. — Certain nutrient media, such as blood serum and the transu- dates of the body (ascitic and hydrocele fluids, etc.), and some fluid food stuffs, require at times to be sterilized and yet cannot be subjected to temperatures high enough to kill spores without suffering injury. The property of spores, when placed under suitable conditions, to germinate into vegetative forms, is here taken advantage of by heating the fluids to 55° or 78° C. for one hour on six consecutive days. By this means, upon each exposure, all the bacteria which have grown in the interval are killed in the vegetative form. Experience has shown that, with few exceptions, this method of fractional sterilization will completely sterilize all fluids thus treated. Pasteurization. — It is often undesirable to expose milk and other food stuffs to such a high tem- perature, because of the deleterious effects produced, and yet a partial sterilization is required. According to the method of Pasteur, however, milk, etc., may be heated for thirty minutes to 70° C, which will kill all vegetative bacteria present, allowing only the spores to remain alive. But even this partial sterilization greatly retards the process of fermentation or putrefaction. Attenuation of Virulence. — Although pathogenic bacteria seem to have retained, for centuries at least, their principal characteristic in producing disease, they have been found to suffer under certain unfavorable outside influences a marked diminution in power, or attenuation of virulence. This loss of power may be effected artificially by several methods, all of which depend upon subjecting the cultures to adverse con- ditions of one kind or another. The first and simplest method is by allowing the cultures to grow old. Ob- viously a pure culture cannot last forever, and in order to retain the virulence of species it is often necessary to subculture upon fresh media. Another S36 mode is to raise the pure culture to a temperature a little below that which destroys the vitality of the organism. A third way is to expose the culture to the action of antiseptic agents. A fourth, but rarely necessary method, is cultivation in the blood of au immune animal. Increase of Virulence. — It is much more difficult to restore lost power or to increase the virulence of bacte- ria than to weaken their toxicity. The method usually employed is by the frequent replanting of cultures or by successive inoculations into susceptible animals! In general, pathogenic virulence is increased by succegl sive inoculation into susceptible animals, and dimin- ished by cultivation in artificial media under unfavor- able conditions. Effect of Chemical Agents. — Many chemical sub- stances when brought in contact with bacteria unite with their cell substance, forming new compounds and usually destroying the life of the organisms. Bacteria are much more easily killed by chemicals when in the vegetative than in the spore stage, and their life functions are inhibited by substances less injurious than those required to destroy their vitality. But both in the vegetative and spore forms they differ considerably in their resistance to chemical agent - The reason for this is but imperfectly understood, but it probably depends upon the composition of tin h cell substance, and is due to a true chemical combina- tion taking place. Chemicals are more destructive to bacteria at a high than at a low temperature, and they act more quickly when the bacteria are suspended loosely in fluids than when in masses. In estimating the extent of the action of chemical agents upon bacteria we usually distinguish the following degrees: 1. Attenuation. — The growth is not permanently interfered with, but the pathogenic and zymogenic functions of the organism are diminished. 2. Asepsis or Inhibition. — The organisms are not able to multiply, but they are not destroyed. 3. Antisepsis, or Incomplete Sterilization.— The vegetative development of the organism is destroyed, but not the spores. _ 4. Disinfection, or Complete Sterilization. — Vegeta- tive forms and spores are destroyed. Many substances which are strong disinfectants become altered under the conditions in which they are used, so that they lose a part, if not all, of t heir germicidal properties. Thus quicklime and milk of lime are disinfecting agents only so long as sufficient calcium hydroxide is present. If this is changed by the carbon dioxide of the air into carbonate of lime it becomes inert. Bichloride of mercury and other chemicals form compounds with many organic and inorganic substances, which, though still germicidal, are much less so than the original substances. Disinfectants. — Among the more commonly used disinfectants may be mentioned: 1. Mineral Disinfectants. — Bichloride of mercury. This substance in the proportion of 1 to 1,000,000 in nutrient gelatin or bouillon, prevents the develop- ment of parasitic bacteria. In the proportion of 1 to 500,000 in water it will kill many species in a few min- utes, but in bouillon twenty-four hours may be needed. With organic substances its power is lessened, so that 1 part in 1,000 may be required. Spores are killed in 1 to 1,000 watery solution within one hour. Corrosive sublimate is therefore less effective as a germicide in alkaline solutions containing much albumin than in aqueous solutions. In such fluids, besides loss in other ways, albuminate of mercury is formed, which is at first insoluble, so that a part of the mercuric salt is reallj- inert. In alkaline solutions, such as blood, blood serum, pus, tissue fluids, etc., the soluble com- pounds of mercury are converted into oxides or hy- droxides. The soluble compounds can therefore remain in solution only when there are present sufficient quantities of certain bodies (the alkaline REFERENCE HANDBOOK OF THE MEDICAL SCIENl ES I! I. lc I l.i ■hlorides and iodides, sodium and ammonium ■hlorides) which render solutions possible. The ad- lition of a suitable quantity of common salt to the 'orrosive sublimate thus prevents the precipitation if tile mercury. Compounds of mercury which, like he cyanides, are not precipitated with alkalies, be- ause they form double -alts, require no addition of • nit. For ordinary use, solutions of 1 to 500 and 1 to [000 of bichloride of mercury will suffice to kill the etativc forms of bacteria within fifteen minut ii much organic matt it is present the .-tronger solu- tion should be used. Biniodide of mercury i- very similar in its effects to the bichloride, and is even more powerful. • in solution has about one-fourth the germicidal value of bichloride of mercury, but nearly same antiseptic value. 3 Iphale of copper has about five per cent, the value of mercuric chloride. S Iphale of iron is a very feeble disinfectant. istic soda in a thirty per cent, solution kills anthrax spores in about ten minutes; in four per cent . solution in about forty-five minutes. rarbonale even in concentrated solution kills spores with difficulty, but at 85° C. it kills spore- in from eight to ten minutes; a five per cent, solution kills the vegetative forms of bacteria in a short time, i Irdinary soap suds have a slight bactericidal as well aarked cleansing effect. The bicarbonate of so- dium has almost no destructive action on bacteria. \in m hydroxide is a powerful disinfectant; the carbonate has little or no germicidal action. A one per cent, solution of calcium hydroxide in water kills bacteria in vegetative form within a few hour-: a three per cent, solution kills typhoid bacilli in one hour; a twenty per cent, solution added to equal parts of feces and thoroughly mixed completely sterilizes them in one hour. Mineral acids, bulk for bulk, are more germicidal than vegetable acids. But any acid which equals 40 c.c. of normal hydrochloric acid will prevent the growth of all species of bacteria and will kill many. Twice this amount destroys most bacteria in a short time. A 1 to 500 solution of sulphuric acid kill< typhoid bacilli within an hour. Hydrochloric, citric, tartaric, malic, formic, and salicylic acids are similar t^ acetic acid in germicidal properties. Boric acid destroys the less resistant bacteria in two per cent, solution and inhibits the growth of others. II. Organic Disinfectants. — Alcohol in ten per cent, solution inhibits the growth of bacteria; absolute al- cohol kills bacteria in the vegetative form in from sev- eral to twenty-four hours. Chloroform, even when chemically pure, does not destroy spores, but a one per cent, solution will kill bacteria in vegetative form. Iodoform has but little destructive action on bacte- ria, and upon most species has no appreciable effect at all. Winn mixed with pus from wounds, etc , iodoform is reduced to soluble iodine compounds, which partly act destructively upon the bacteria and partly unite with the poisons produced by them. Carbolic acid in aqueous solutions 1 to 1,000 inhibits the growth of bacteria; in the proportion of 1 to 400 it kills the less resistant organisms, and in 1 to 100 solution destroys all vegetative forms. A five per cent, solution kills the less resistant spores in a few hours and the more resistant in from one day to four weeks; a slight increase of temperature aids the de- structive action. A three per cent, solution kills strep- tococci, staphylococci, anthrax bacilli, etc., within one minute. Carbolic acid loses much of its value when in solution with alcohol or ether, but the addition of 0.5 per cent, hydrochloric acid aids its activity. Carbolic acid is so permanent and comparatively so little influ- enced by the presence of albumin, that it is one of the best agents for general use in practical disinfection. Cresol is the chief ingre -called " crude car- bolic acid." It is al si insoluble in water and has therefore little germicidal value. Mixed with equal parts of sulphuri render it soluble it i- a power- ful disinfectant, but it i- then strongly corn. Creolin i- an alkaline emulsion of tin- cresols and other products contained in crude carbolic acid with snap, ami is as powerfully disil pure carbolic acid; it is used in live per cent, emulsions. Lysul is similar to creolin and has about the same germicidal value. TricTi \ol i- a refined mixture of the three en (meta-, para-, and orthocresol) ; it is soluble in water to the extent of 2.5 per cent., and is about thi as s( rung as carbolic acid. The many of them, possess marked germicidal propei ii Methyl violet ami malachite green destroy the typhoid bacillus in bouillon cul- tures in 1 to .'Oil solution in two hours, ami the pyo- genic cocci in less time. Even in 1 to 100,000 solution they are -aid In inhibit bacterial growth. The essential oils an- also strongly disinfectant. The oils of cinnamon, clove.-, thyme, -am la I v. I. it. . oy most bacteria in from one to twelve hours. Thymol and eucalyptol have about one-fourth the strength of carbolic acid, t > i L of peppermint in 1 to .Union inhibits bacterial growth. Oil of turpen- tine in 1 to 200 solution does t ho same. Camphor has very little anti.-eptic action. (See also article on I> Is.) III. Gaseous Disinfectants. — Formaldehyde is a gaseous compound of strongly disinfectant properties and posse 1 of an extremely irritating odnr. At a temperature of 68° F. the gas is polymerized, that i- in say, a second body is formed composed of a union of two molecules of CH 2 0. This is known as "para- formaldehyde," and is a white soapy substance, soluble in boiling water and alcohol; it exists in the solution of commerce ordinarily called "formalin," which is a clear watery liquid containing from 33 to 40 per cent, of the gas and 10 to 20 per cent, of methyl alcohol, its chief impurity. When this is concen- trated, about 40 per cent, paraformaldehyde results. Pried over sulphuric acid a third body — "trioxy- methylene" — is produced, consisting of three mole- cules of CH,0, and is a white substance almost in- soluble in water or alcohol, and giving off a strong odor of formaldehyde. The solid polymers of form- aldehyde when heated are again reduced to the gaseous condition; ignited they finally take fire and burn with a blue flame, leaving but little ash. Formaldehyde has an active affinity for many organic substances and forms with snme of them defi- nite chemical combinations. It combines readily with ammonia to produce a compound called ammoniacal aldehyde which possesses neither odor nor the anti- septic properties of formaldehyde. This action has been made use of in neutralizing the odor of for- maldehyde when it is desired to dispel it rapidly after disinfection of habitations. Formaldehyde also forms combinations with certain aniline colors, viz., fuchsin and safronin, modifying their shades. The most delicate fabrics of silk, wool, cotton, fur, leather, etc., however, are unaffected in texture or color by formal- dehyde. Iron and steel are attacked after long exposure to the gas or its solution: but copper, brass, nickel, zinc, silver, and gold work are not at all acted upon. Formaldehyde unites with nitrogenous prod- ucts of decay, fermentation, and putrefaction, form- ing true chemical compounds, which are odorless and sterile. It is thus a complete deodorizer. Formal- dehyde has a peculiar action upon albumin, which it transforms into an insoluble and indecomposable substance. It is to this property of combining chem- ically with albuminous substances forming the proto- pla-in of bacteria that formaldehyde owes its ger- micidal powers. It is also an excellent preservative of S37 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES organic products for the same reason; and use has been made of it to preserve meat, milk, and other food products. But according to Trillat and others it renders these substances indigestible and unfit for food. It has been successfully employed, however, as a preservative of botanical, pathological, and histological specimens. The vapors of formaldehyde are extremely irritating to the mucous membrane of the eyes, nose, and mouth, causing profuse lacrymation, eoryza, and secretion of saliva. Aronson has stated that rabbits and guinea- pigs, allowed to remain for twelve to twenty-four hours in rooms which were being disinfected with formal- dehyde gas, were unaffected by the fumes. But other experimenters have found that animals, such as dogs, cats, etc., accidentally exposed for some time to the action of the gas, suffered severely, and some have died from its effects. It would seem, therefore, that although formaldehyde is comparatively non- toxic to the higher forms of animal life, nevertheless a certain degree of caution should be observed in its use. Roaches, flies, bedbugs, and other insects are, as a rule, not killed by formaldehyde gas in the process of disinfecting a room. The results of numerous experiments in practical disinfection with this agent have shown that two and one-half per cent, by volume of the aqueous solution of formaldehyde, or one per cent, by volume of the gas, is sufficient to destroy the vegetative forms of patho- genic bacteria in a few minutes, when they are freely exposed to its influence and in a moist condition. The germicidal power of the gas depends not only upon its concentration, but also upon the temperature and the condition of the object to be sterilized. As with other gases, it has been found that the action is much more rapid and complete at higher temperatures (35° to 45° C), and when the test objects are moist and freely exposed, than at lower temperatures and when the objects are dry and in mass; the gas possesses when dry little or no penetrative power. Still it has been repeatedly demonstrated that it is possible to disinfect the surface of rooms and articles contained in them, under the conditions of temperature and moisture ordinarily found, by an exposure of a few hours to a saturated atmosphere of the gas. Sulphur dioxide gas has been extensively used for the disinfection of hospitals, ships, apartments, etc. Its action depends upon the formation of sulphurous acid in the presence of moisture. In its pure state S0 2 does not destroy spores, and even on vegetative forms its germicidal effect is uncertain. An exposure, however, for eight hours to an atmosphere containing at least four volumes per cent, of this gas in the pres- ence of moisture will destroy most, if not all, the com- mon non-spore-bearing pathogenic bacteria. It is not so prompt or powerful in its action as formalde- hyde gas, which in many respects is a preferable dis- infectant, especially in cases where the sulphurous acid formed from the sulphur dioxide may have an injurious effect upon the articles to be disinfected. Peroxide of hydrogen is an energetic disinfectant, and in two per cent, solution (about forty per cent, of the ordinary commercial article) will kill the spores of anthrax in from two to three hours. A twenty per cent, solution of good commercial peroxide of hydrogen will quickly destroy the pyogenic cocci and other non- spore-bearing bacteria. On account of its rapidity of action and non-poisonous character it is a useful and safe disinfectant, but it combines with organic matter and becomes inert, being apt to deteriorate if not prop- erly kept. Chlorine is a powerful gaseous germicide, owing its activity to its affinity for hydrogen and consequent release of nascent oxygen, when it conies in contact with microorganisms in a moist condition. Like formaldehyde gas and sulphur dioxide it is much more active in presence of moisture than in a dry condition. Dried anthrax spores exposed for an hour in an 838 atmosphere containing 44.7 per cent, of dry chlorine were not destroyed; whereas when the spores were previously moistened and exposed in a moist atmos- phere for the same time, four per cent, was effective and when the time was extended to three hours, one per cent, destroyed their vitality. The anthrax bacillus, in the absence of spores, was killed by an exposure in a moist atmosphere containing 1 part to 2,500 for twenty-four hours. In watery solution 0.2 per cent, kills spores within five minutes, and the vegetative forms almost immediately. Chloride of lime owes its efficacy to the chlorine it contains in the form of hypochlorites. A solution of one-half to one per cent, of fresh chloride of lime in water will kill most bacteria in from one to five minutes; a five per cent, solution usually destroys spores in an hour. Bromine and iodine are of about the same germicidal value as chlorine, in the moist condition; but, like chlorine, they are not applicable for general use in house disinfection on account of their poisonous and destructive properties. They are useful for the disinfection of sewers, and other similar places. Trichloride of iodine in 0.5 per cent, solution destroys the vegetative forms of bacteria in about five minutes, (The relation of bacteria to disease — infection, immunity, etc. — will be considered elsewhere; as will also the subject of Bacteriological technique.) Special Bacteria. Under this heading will be described the chief characteristics of the more important bacterial species pathogenic for man and other animals. There are many bacteria which have been found in certain diseases, but their causal relation to the disease has not yet been proven, and they have also been found in other affections. These we cannot treat of here. Nor will space allow us to consider the non-patho- genic species, or those which do not affect man, but are pathogenic for the lower animals only. The Tubercle Bacillus (Koch's Bacillus tubercu- losis). — The infectious nature of tuberculosis was first demonstrated by Villemin in 1865, when by inoculation with tuberculous material he communi- cated the disease to healthy susceptible animals. In 1882 Koch discovered the Bacillus tuberculosis, which is now known to be the specific cause of the disease. Microscopical Appearances. — The tubercle bacillus occurs in sputum and in cultures as slender rods from 1.5 to 4 [i long and about 0.3 a broad, often slightly curved. The bacilli usually occur singly, but in cultures sometimes form chains of four to six elements; occasionally peculiar, club-like forms and branches have been met with, from which they have been supposed to be allied to the actinomyces group of fungi or streptothrices (see Plate VIII., Fig. 1). Motility. — Non-motile. Spore Formation. — The clear spaces or vacuoles which are present in stained preparations, and which have been described by some authorities as spores, are probably due to degenerative processes, as they do not show the form of spores nor is anything known as to their power of resistance or germination. Staining Reaction. — The tubercle bacilli stain with difficulty, but once stained they retain the dye with great tenacity. At present the methods most com- monly employed for staining tubercle bacilli, though there are many modifications of these, are the Ziehl- Neelsen with carbol fuchsin, and the Koch-Ehrlich with aniline water and gentian violet. For special methods of preparing and staining cover-glass speci- mens and sections, see Bacteriological Technique. The peculiar staining reaction found in the case of the bacillus tuberculosis is not confined to that organism alone, as other similar organisms, when REFERENCE HANDBOOK OF THE MEDICAL SCI] \< I 9 Bacteria treated in like manner, react in the same way. Thus it has in be differentiated from the smegma bat located in the smegma often seen beneath the prepuce and upon the vulva, both normally and in disease; Lustgarten's bacillus of syphilis found principally in the primary lesions associated with that disease; the bacillus of loprosy; ami acid-resisting or grass bacteria found in butter. Hueppe differentiates tin- first three organisms and the tubercle bacillus a^ follows: 1. Treat the preparation, stained with carbol fuchsia with sulphuric acid, and Lustgarten's bacillus. if present is at once decolorized. 2. If not immediately decolorized, treat with alcohol and if it is the smegma bacillus it will lose color. :i. If it is still not decolorized, it is either the leprosy or the tubercle bacillus. According to Baumgarten, the leprosy bacillus is stained by an exposure of six or seven minutes to a cold saturated watery solution of fuchsin and retains the stain when subsequently treated with acid alcohol (nitric acid 1 part to alcohol 10 parts). When treated for the same length of time, the tubercle bacillus does not ordinarily become stained. Biological Characters. — Aerobic; does not grow in the absence of oxygen. Growth takes place between 29° and 42° C; optimum temperature at 37° C. Fader all circumstances the growth is slow. On the ordinary agar and gelatin culture media development is very scanty; for the cultivation of tubercle bacilli practically the only media employed are coagulated blood serum and four to six per cent, glycerin agar and glycerin bouillon. It is very difficult to obtain a pure culture of tubercle bacilli, because they grow so slowly and require for their development an incubator temperature, and because owing to the slow growth, the other bacteria present in tuberculous material, as sputum, grow more rapidly and take possession of the culture medium before the tubercle bacillus has had time to form colonies. It is therefore best, unless human tissues can be obtained free from other infection, first to inoculate guinea-pigs (which are very susceptible) both subcutaneously and intraperitoneally, with the sputum, and then to obtain cultures from the animal as soon as the tuberculous infection has fully devel- oped. The animals thus inoculated usually die at the end of three to four weeks or more. It is better, however, to kill a guinea-pig which by its enlarged glands shows evidence of tuberculosis, and to remove, with the greatest antiseptic precautions, one or more nodules from the lungs, spleen, or lymphatic glands, and inoculate with this the solid culture medium (blood serum) by rubbing it directly over the surface; or a part of it may first be crushed between two sterilized glass slides and then transferred to the serum and gently rubbed over its surface. Growth on Coagulated Blood Serum {Dog or Bovine Serum) or on Egg. — On this medium, which is gen- erally employed to obtain the first culture, the growth becomes visible after ten to fourteen days at 37° C, and at the end of three to four weeks a distinct, characteristic development has occurred. Small, grayish-white, dry, crumbly scales first appear on the surface; then as development progresses there is formed an irregular, membranous-looking layer. On removing a small portion of this and placing it on a cover glass without rubbing, then staining and examin- ing under the microscope, the bacilli will be seen to present a characteristic appearance and to be arranged in parallel rows of variously curved figures. Growth on Glycerin Agar. — Owing to the greater facility of preparing and sterilizing glycerin agar, and the more rapid and abundant development of the bacilli, which have become accustomed to growth outside the body, this medium is now usually em- ployed in prefer to blood serum preserving cultures. At the end of fourteen to twenty-one daya the developmenl is more luxuriant than upon blood -'■nun after several weeks. When numerous bacilli ha\ e been distributed over the surface of the medium, a rather uniform, thick, white layer, which later be- '■ a yellowish in color, is developed; when the bacilli are few in number, separate colonies ar« developed with more or less irregular outlini Growth on Glycerin Bouillon. — On bouillon con- taining about five per cent, of glycerin the tubercle bacillus also grows readily if a fresh thin film of grow th from the glycerin agar is floated on the surface. '1 his medium is used for the production of "tuberculin." The small piece ol pellicle removed from the previous culture continues to enlarge while it floats on the surface of the liquid, and in the course of from three to six weeks covers it completely as a single film, which on agitation breaks up and settles to the bottom of the flask, where it ceases to develop fur- ther. The liquid remains clear, containing in solution the products formed by the growth of the bacillus. Vitality. — Tubercle bacilli in pure cultures are very susceptible to the action of direct sunlight, being destroyed in from a few minutes to some hours, according to the thickness of the growth. Exposed to diffuse daylight they are killed in a week. Though they do not form spores, so far as known, the bacilli have a somewhat greater resisting power to heat and desiccation than many other pathogenic bacteria, frequently retaining their virulence in a dried condi- tion at the ordinary temperatures for months. Portions of the lung from a tuberculous cow, dried and pulverized, produced tuberculosis in guinea-pigs at the end of one hundred and two days. Dried tuberculous sputum may retain its virulence for two or three months or more. An instance is reported by Ducor of a healthy family having become infected with tuberculosis from living in a room which had been occupied by a consumptive patient two years before, and on examining the sputum-stained wall- paper not only were tubercle bacilli found in it, but when guinea-pigs were inoculated with it they died of the disease. Exposure to 100° C. dry heat does not kill the bacilli in twelve hours; but moist heat at 60° C. destroys them in fifteen minutes. Cold has little or no effect upon them. The resisting power of this bacillus against chemical disinfectants is considerable, espe- cially in sputum, where the organisms are protected by mucus from penetration by the germicidal agent. They are not always destroyed by the gastric juice in the stomach, as has been shown by successful experiments in feeding to susceptible animals. They are killed in sputum in about six hours by an equal amount of a three per cent, solution of carbolic acid, and in about one hour by a five per cent, solution. Bichloride of mercury is unsuitable for the disinfec- tion of sputum unless used in very strong solution (1 to 500). Pickling and smoking are said not to destroy the virulence of tuberculous meat. Occurrence. — The tubercle bacillus is a strict parasite — that is to say, it does not grow under natural conditions outside of the bodies of man and animals. It has frequently been found, however, in the dust of hospitals, dwellings, railways, street cars, etc., in places where consumptives have expectorated. Very rarely has it been found in the air. The milk of tuberculous cows, even when the udder is not affected, very often contains tubercle bacilli; they are also found in butter. Postmortem examinations of many individuals who have died from some other cause than tuberculosis have revealed the presence of healed tuberculous foci. It has been estimated that sixty-six per cent. of all mankind have some evidence of tuberculosis, old tuberculous lesions, of primary or secondary origin. Tubercle bacilli are said to have been found 839 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES also in the secretions of the nose and throat of healthy persons, nurses and doctors, who have been in con- stant association with tuberculous patients. The tubercle bacillus is the essential cause of all forms of tuberculosis: the various affections of the lungs and other organs, lupus, scrofula, and inflamma- tion of the bones and joints. The following diseases have also been traced to tuberculous infection: so- called "inoculation lupus," tuberculosis verrucosa cutis, and scrofuloderma; choroidal tuberculosis, idio- pathic pleurisy, etc. Indeed, all organs and portions of the body may become affected with this disease. Many cases of tuberculosis are produced by the tubercle bacillus alone, but very frequently strepto- cocci and other pyogenic cocci play an important part in the production of fever and the destruction of tissue, as in phthisis, by suppurative processes. Tuberculosis is very common among cattle, chiefly in cows and rarely in calves. According to Klepp, from abattoir inspections in Germany, up to thirty- five per cent, of cattle, eighty per cent, of cows, and three per cent, of calves, are commonly found tubercu- lous. The disease is also quite frequent in young pigs; less so in sheep, goats, horses, dogs, and cats. Rab- bits and guinea-pigs are also not uncommonly spontaneously affected with tuberculosis, when kept in cages together with infected animals. Monkeys in confinement almost invariably die from tubercu- losis. Wild animals are comparatively free from the disease; and so are birds, except canaries and parrots. Pathogenesis. — As seen from the above many animals besides man are naturally susceptible to tuberculosis. Among test animals guinea-pigs are the most susceptible, and on this account they are com- monly used for the detection of tubercle bacilli in suspected material by inoculation. When inoculated with the minutest quantity of living tubercle bacilli they usually succumb to the disease. Infection is most rapidly produced by intraperitoneal injection, d ■ath following a large dose in from ten to twenty days. On autopsy the omentum is found to be con- stricted in sausage-like masses and converted into hard knots containing many bacilli. There is often no fluid in the peritoneal cavity, but generally in both pleural sacs. The spleen is enlarged, and the various organs contain tubercle bacilli. After smaller doses death may be deferred from four to eight weeks, when the peritoneum and interior organs are found to be filled with tubercles. On subcutaneous injection into the abdominal wall there is thickening of the tissues about the point of inoculation, which breaking down in a week leave a sluggish ulcer covered with cheesy matter. The neighboring lymph glands are swollen, and after two or three weeks they may attain the size of hazelnuts. Soon an irregular fever is set up, and the animal becomes emaciated, usually dying within four to eight weeks. If the injected mate rial contain only a few bacilli, the wound at the point of inoculation may heal and death be postponed for a long time. The lymphatics undergo cheesy degen- eration, the spleen is much enlarged, and throughout its substance, which is dark red in color, are masses of nodules. The liver is also enormously swollen, streaked brown and yellow, and the lungs are filled with grayish tubercles; but the kidneys, as a rule, contain no tubercles. Tubercle bacilli are always found in the diseased tissues, but the more chronic the process the fewer are the bacilli present. Rabbits are also quite susceptible to tuberculosis by inoculation, but much less so than guinea-pigs. In these animals death almost always follows injection of tuberculous material into the anterior chamber of the eye; producing local lesions, softening of the neighboring lymph glands, lesions of the lungs, general miliary tuberculosis, and death in several wi'cks or months. Subcutaneous inoculations are very much less effective; but intravenous and intra- peritoneal inoculations usually cause general tubercu- losis and death in a few weeks. Field mice and cats are also readily infected by artifical inoculation; rats, white mice, and dogs only when very large doses are given. Canaries and parrots are susceptible; fowls and pigeons only slightly so; and other birds and cold- blooded animals are apparently immune. Besides the artificial modes of infection already alluded to, tuberculosis may be produced in animals susceptible to the disease by feeding them with tuber- culous material. This has been repeatedly done with milk, sputum, etc., containing tubercle bacilli. Here evidence of infection is usually shown in the mesen- teric glands before the intestinal walls are affected; indeed, there may be no local lesions in the intestines at all. Under such conditions, infection is probably caused by absorption of the poisons through serous or mucous membranes. The experimental production of tuberculosis by inhalation of bacilli has been demonstrated by Koch in guinea-pigs, rabbits, mice, etc. In these cases the bacilli were usually administered in the form of fine spray; the inhalation of dry tuberculous dust has seldom proved experimentally successful. The tubercle bacillus acts upon the tissues by means of the poisons which it produces as the result of its growth. Soon after entrance into the tissues of either living or dead bacilli, the cells surrounding them begin to show signs of irritation. The connect- ive-tissue cells become swollen and undergo mitotic division, the resultant cells being distinguished by their large size and pale nuclei. A small focus of proliferated epithelioid cells is thus formed about the bacilli, and according to the intensity of the inflamma- tion these cells are surrounded by a larger or smaller number of the lymphoid cells. When living bacilli are present and multiply, the lesions progress, the central cells degenerate and die, and a cheesy mass results, which later may lead to the formation of cavities. Dead bacilli, on the other hand, give off sufficient poison to cause less marked changes only, and never produce cavities. Of the gross pathological lesions produced in man by the tubercle bacilli the most characteristic are small nodules, the so-called miliary tubercles. These when young, and before they have undergone degeneration, are gray and translucent in color, somewhat smaller than a millet seed in size, and hard in consistence. But miliary tubercles are not the sole tuberculous products. The tubercle bacilli may cause the diffuse growth of tissue identical in structure with that of miliary tubercles — that is. composed of a basement substance containing epithelioid, giant, and lymphoid cells. This diffuse tubercle tissue also undergoes cheesy degeneration. When caseation is rapidly spreading, as in acute tuberculosis, the bacilli are usually abundant, being scattered in irregular groups through the tissues. Occasionally they are found in the leucocytes, and in the giant and epithelioid cells. The more chronic the lesions the fewer they are in number. Modes of Infection. — The chief modes of infection by the tubercle bacillus are through the respiratory tract or the intestines, more rarely through wounds of the skin, and still more rarely through the sexual organs. Pulmonary tuberculosis, as a primary infection, and not occurring in young children, may be considered to be caused chiefly by the direct transmission of tubercle bacilli through kissing, soiled hands, handkerchiefs, etc., or by the inhalation of tuberculous dust. Intes- tinal and mesenteric tuberculosis, which is rare among adults and common with children, is probably due not only to swallowing the bacilli received in the above-mentioned ways, but also to the ingestion of tuberculous milk. Lupus is probably always pro- duced by the inoculation of tubercle bacilli on the skin or mucous membranes, the original seat of the disease being often on a wounded surface. Localized skin tuberculosis is sometimes produced by accidental Sill REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria aoculation at autopsies. The transmission of in- ection through the sexual organs of the mule or emale, though possible, is extremely rare. There ,.. to b<- some evidence of the communication of uberculous infection from the mother to the fetus in mimals; and two rases are recorded of probable ilacental tuberculosis in the human fetus. But we ao reason to suppose that infection of the ivum of healthy mothers from the paternal side ever occur, even when the father has tuberculosis of be scrotum or seminal vesicles. The mere fact that statistics show a greater frequency of tuberculous [iseases in children during the first than in the follow- ears of life does not strengthen the hypot hesis of tion in ulero; for nursing babies would naturally ... i posed to infection through the moth milk and through personal contact than others; and, besides, the more tender the life of the infant the more eptible it would be ordinarily to indirect infection a t uberculous mother. By far the commonest mode of infection, therefore, is undoubtedly by means of tuberculous sputum, which, being coughed up by consumptives and care- . expectorated, dries and distributes numerous virulent bacilli in the dust. As long as the sputum remains moist there is no danger of dust infection, but only of direct contact. A great number of the ex- pectorated and dried bacilli very probably die, espe- cially when exposed to the action of direct sunlight ; but when we consider the enormous masses which are expectorated,* it is evident that a sufficient quantity remains alive to produce infection in the immediate vicinity of consumptives unless precautions are n to prevent it. There is comparatively little danger of infection in the streets or at a distance from consumptive patients, because even if present in the . the tubercle bacilli have become so diluted that they are not much to be feared. It may, therefore, be said that the probability of infection from tubercu- losis in general is not so great after all, but at the same time it is all the more to be dreaded and guarded against in the immediate neighborhood of consump- tives. Those who are most liable to infection from this source are the families, nurses, fellow-workmen, fellow-prisoners, etc., of persons suffering from the disease. In this connection, also, attention may be drawn to the fact that rooms which have been re- cently occupied by consumptives are not infrequently the means of producing infection (as has been clinic- ally and experimentally proved) from the deposition of tuberculous dust on furniture, walls, floors, etc. Fliigge has lately pointed out that in coughing, sneez- and even in speaking, very fine particles of secretion, containing tubercle bacilli, may be thrown out and carried by air currents many feet from the patient and remain suspended in the air for a con- siderable time. For this reason consumptives should be careful to hold their hands or a handkerchief before their mouths, or at least avoid as much as possible contaminating other persons with whom they come in contact. Phthisical sputum, however, cannot be held re- sponsible for the occurrence of all human tubercu- losis. .Milk also serves as a frequent conveyer of infection, whether it be the milk of nursing mothers suffering from consumption or the milk of tuberculous cows. The transmission of tubercle bacilli in the milk of tuberculous cows has been abundantly proved by feeding and inoculation experiments on animals. Formerly it was thought that in order to produce infection by milk there must be local tubercu- lous infection of the udder; but it is now known that tubercle bacilli may be found in milk when an internal organ is infected, and when no disease of the * Xuttall has estimated that from one and one-half to three billion virulent tubercle bacilli may be expectorated by a single tuberculous individual in twenty-four hours. udder, so far a j careful is The milk of all cows, then fore, which have any tuber- culous infection whatever, m considered as ibly containing tubercle bacilli. 'With regard to the flesh of tuberculous cattle, ti conditions hold g 1 as in the infection by milk, only the danger iderably less from the fact thai meat I cooked, and also because the muscular ti seldom attacked. In view of the great rtality from tuberculous diseases among mankind, legi lative control and inspection of cattle and milk would seem to be an absolute necessity. A- a practi- cal and simple method of preventing it e pecially among children, the sterilization (by hi of the milk used as food must commend itself to all. With regard to bovine infection in man numerous investigations have been made. To Ravenel properly belongs the credit, of isolating the firsl bovine bacillus from a child. It has been shown that children are especially the ones infected, and usually the point of entry is clearly alimentary. Cervical adenitis and abdominal tuberculosis are the most frequent types of infection. Generalized tuberculosis due to bovine infection is less frequent and bone and joint, tubercu- losis is almost exclusively of the human type, infec- tion of adults is very uncommon. According to I'arth, a careful study of all the factors leads to the belief that about ten per cent, of all tuberculosis in children under five is due to bovine infection. Individual Susceptibility. — Another most important factor in the producion of tuberculosis, as of all infec- tious diseases, is individual susceptibility. That this susceptibility or "predisposition," improperly so called, may be either inherited or acquired is now an accepted fact in medicine. There is no doubt that great differences exist in different persons in their susceptibility to tuberculosis, as there are also differences in the intensity of the tuberculous process in the lung. The fact that individuals contracting tuberculosis from the same source are attacked with different severity, and that there is, as a rule, no great variation in degrees of virulence in the tubercle bacilli of different origin, shows that this depends upon something else than a variation in virulence of the infection. The results of postmortem examina- tions also demonstrate that many cases of pulmonary tuberculosis evidently occur without showing any visible signs of disease, and heal spontaneou-ly. The possibility of favorably influencing, in an existing tuberculosis, "the course of the disease by treatment proves, too, that under natural conditions there is a varying susceptibility. Clinical experience teaches likewise, that the children born of tuberculous parents, and persons living in poor hygienic conditions and depressing surroundings, as in prisons, asylums, and convents, and those suffering from exhausting diseases, more especially bronchial affections, diabe- tes, typhoid fever, etc., are more susceptible to tuberculosis than others not so situated or affected. Animal experiments, moreover, have shown that not only are there differences of susceptibility in various species, but also an individual susceptibility in the same species. The doctrine of individual suscepti- bility, therefore, is apparently founded on fact, although the reasons for it are only partially understood. Immunization: Koch's Tuberculin. — As in other infectious diseases, many attempts have been made to produce an artificial immunity against tubercu- losis, but so far the results have been unsatisfactory. Among the numerous agents that have been tried to protect animals against the action of the tubercle bacillus, the most important is Koch's tuberculin. Tuberculin contains all the products of the growth of the tubercle bacillus in nutrient bouillon and certain substances extracted from the bodies of the bacilli themselves; also the albuminoid and other materials 841 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES originally contained in the bouillon which are unaf- fected by the growth of the bacilli. There are two preparations known respectively as the "old" or original ("T. O.") and the "new" tuberculin or "tuberculin T. R.," or Bacillus Emulsion (" B. E."). Old tuberculin is prepared as follows: The tubercle bacillus is cultivated in peptone-glycerin-bouillon. At the end of from three to six weeks, according to the rapidity with which the culture grows, an abund- ant development takes place with the formation of a thick, dry, white crumpled layer, which finally covers the entire surface of the bouillon. (It was originally inoculated on the surface.) After development ceases, this layer breaks up and sinks to the bottom of the flask. Fully developed cultures, having been tested for purity by microscopical examination, are evaporated by boiling to one-tenth of their original bulk. The liquid is then filtered, and the crude tuberculin thus obtained contains forty to fifty per cent, of glycerin (the broth medium contained four to five per cent.), and keeps well, retaining its activity indefinitely. This substance when injected into tuberculous individuals affects the tuberculous process in a peculiar way. Very small doses produce a moderate increase of inflammation with slight elevation of temperature in tuberculous persons, while healthy individuals have neither fever nor marked local symptoms. The following is the method of treatment employed. After each injec- tion, which should be large enough to cause a slight but not a great rise of temperature, a noticeable change in the tuberculous process results. The amount of tuberculin injection is constantly increased, so as to continue the moderate reactions. After several months all reactions cease, the patients having become temporarily immune to the toxin, but not to the growth of the bacillus. Further injections are now useless, until this immunity has passed. Inasmuch as the bacilli themselves have not been directly affected by the treatment, when this is inter- rupted the tuberculous process is apt to progress (Koch). Although Koch and some of his followers appar- ently, from their reports, obtained satisfactory results in the treatment and immunization of man and animals with old tuberculin, the majority of invest i- gators, after a short period of enthusiasm, abandoned its use as very rarely beneficial, if not often injurious. Koch therefore attempted to improve his method and recommended a new preparation under the name of "Tuberculin T. R.," or new tuberculin or Bacillus Emulsion (" B. E "). The substances produced in the body by the old tuberculin neutralized the tuber- culous toxins, according to Koch, but were not bac- tericidal. This he considered due to the nature of the envelope of the tubercle bacillus, which rendered it difficult to obtain the substance of the bacilli in soluble form without so altering it by heat or chemicals that it was useless for immunizing purposes. Immunity, he thought, was not produced in man for similar rea- sons, the bacilli never giving out sufficient toxin, per- haps, to bring about the production of curative sub- stances. He therefore decided to grind up the dried bacilli and soak them in water, and thus obtain, if if possible, without the aid of heat, a soluble extract of the cell substance of the bacilli, which he hoped would 1«- immunizing. Buchner, by crushing under a great pressure tubercle bacilli mixed with sand and thus squeezing out their protoplasm, obtained a simi- lar substance, which he called "tuberculoplasmin." The new tuberculin is thus a watery extract of the soluble portions of the unaltered tubercle bacilli. Owing to the method of preparation, it is evident that contamination is difficult to avoid, freedom from intact bacilli is uncertain, and the strength of the solution is variable. Twentv per cent, of glycerin is added to preserve the preparation. Dilutions are 842 made in 0.5 per cent, carbolic acid in O.S salt solution Before marketing the preparation is usually subieetpri to heating at (30° C. ""jeciea Bouillon Filtrate Tuberculin ("B. F."). This i s the unheated filtrate from bouillon cultures of human tubercle bacilli, suggested by Denys. Many other tuberculins have been proposed during the last twenty years, all of which are vaccines made from either the body substance of the germ or the liquid medium in which it has grown, or both, and their aim is to stimulate the defensive resources of the system or to induce antitoxic and antibacterial immunity They all produce, when given in sufficient doses local reactions in tuberculous foci, and the well-known but little understood phenomena of general tuberculin reaction. These new tuberculin preparations are now considered superior to those obtained from the older product of Koch in the treatment of human tuberculosis. Regarding the results from tuberculin treatment it has been demonstrated by bitter experience that tuberculin is not the vaunted and long-looked-for specific it was at first thought to be. Trudeau, and other reliable investigators, however, have formed favorable impressions of its influence by noticing that the disease seemed to progress more rarely with the usual exacerbations and relapses in patients who were tolerating the tuberculin treatment than in those who had the climatic and open-air treatment only. The chief use to which the old or original tuberculin has been put is as an aid to the diagnosis of obscure cases of tuberculosis in cattle and man, and for this purpose it has proved to be of inestimable value. Cows are generally injected subcutaneously with 0.3 to 0.5 c.c. (diluted with water to 30 or 50 c.c.) of tuberculin and watched to see whether there is a rise of temperature of 1.5° to 3° C. in twelve to fifteen hours. Occasionally the reaction does not occur when the animals are in an advanced stage of the disease, but in such cases the test is not needed. The reaction never takes place, or one very much less marked occurs, in healthy animals, though small centers of infection are often difficult to locate later on autopsy. Latent tuberculosis is rarely if ever stimulated to renewed activity. It is important to note that an animal frequently requires an interval of a month to give a second positive reaction, if it has reacted typically on the first trial. In man it is, of course, much more difficult to form any opinion as to the reliability of the tuberculin test, from the fact that it cannot be controlled by postmortem examina- tions. It, is, however, of great value in selected cases, both surgical and medical, where slight tuberculosis is suspected, and yet no decision can be reached. In the first small dose advised (0.5 mgm. in adults and 0.3 in children) an absolutely latent infection should usually give no rise of temperature. Von Pirquet's cutaneous tuberculin test has for many purposes supplanted the subcutaneous injec- tions, as it is perfectly harmless. This is carried out by placing a drop of a 25 or 50 or 100 per cent, solution of tuberculin upon the skin of the forearm and then with a needle or instrument making through it a slight abrasion without drawing blood. A central abrasion without tuberculin is made at another point. Within twelve to twenty-four hours a papule with a surrounding congested area forms about the inocu- lated point. In Moro's test equal parts of tuberculin and lanolin are mixed together to make an ointment, which is rubbed upon the skin. A crop of papules develops in twelve to twenty-four hours in cases in which the test proves effective. In the ophthalmo- tuberculin test, two solutions of different strengths are employed, one of the alcohol precipitate of tuber- culin in 0.5 per cent, and 1 per cent., and the other of 1 and 2 per cent, tuberculin ("T. O."). The REFERENCE HANDBOOK OF THE MEDICAL S< [EN( ES Bacteria weaker and stronger are used successively ineacheye. In from three to twelve hours, or longer, reaction occurs, unci occasionally conjunctivitis, keratitis, or iritis results. Preference is therefore given to the cutaneous tes( . Haragliano and others claim to have obtained with an antituberculous scrum, prepared chiefly from horses, encouraging results; and Behring hopes to be able to make an antitoxic serum which will be curative and protective. Rut whether serum therapy is destined to solve the problem of the treatment ol tuberculosis remains for the future to decide. Judg- ing, however, from the progressive nature of the disease, there is not much ground to hope for the abundant development of curative substances in the blood of animals. Meanwhile all energies should be directed to the prevention of tuberculosis, nol only by the enforce- ment of proper sanitary regulations as regards the care of sputum, milk, meat, disinfection, etc., but also by continued experimental work and by the establishment of consumptive hospitals; and by efforts to improve the character of the food, dwellings, and condition of the people in general we should endeavor to build up the individual resistance to the disease. It may be years yet before the public are sufficiently educated to cooperate in adopting the necessary hygienic measures to stamp out tuberculosis entirely; but from the results which have already been obtained in reducing the mortality from this greatest scourge of the human race, we have reason to hope that in time it may be completely eradicated. The Leprosy Bacillus (Bacillus lepra:). — This organism, discovered by Hansen in 1879, is found chiefly in the interior of the peculiar round and oval cells met with in leprous tubercles. The bacilli have also been observed in the lymphatic glands, liver, spleen, and testicles, and in the thickened portions of nerves involved in the anesthetic forms of the disease. According to some authorities they occur likewise in the blood. The bacilli lie in the leprous cells in great numbers, and also in the lymph spaces outside of these cells. They are not found in the epidermal layers of the skin, but, according to Babes, they may penetrate the hair follicles. Microscopical Appearances. — The bacillus lepra? resembles the tubercle bacillus in form, but is some- what shorter and not so frequently curved. The rods have pointed ends; and in stained preparations, unstained spaces, similar to those observed in the tubercle bacillus, are seen. (See Plate VIII., Fig. 2.) Motility. — Non-motile. Staini?tg Reactions. — The leprosy bacillus cannot be positively differentiated from the tubercle bacillus by staining reactions. It stains readily with the a liline colors and also by Gram's method. Although di.Tering from the tubercle bacillus in the ease with which it takes up the ordinary aniline dyes, it behaves like the former in the manner in which it retains its color when subsequently treated with strong solutions of the mineral acids and alcohol. Inasmuch as leprosy and tuberculosis not infrequently occur together in the same person (according to Hansen and Looft tuberculosis being the cause of death in forty per cent, of the cases of leprosy), in making a differen- tial diagnosis, all the various points, histological and pathological, must be considered and animal inoculations made, in addition to microscopical examination. Biological Characters. — Attempts to cultivate the bacillus lepne have frequently been made, but so far with only questionable results, as none of the cultures obtained has produced a similar disease when inocu- lated into animals. The etiological relation of this bacillus to leprosy is based, therefore, chiefly upon its constant presence in the leprous tissues. It has been shown by Spronk, however, thai the blood serum of many lepers even in weak dilution give-, the agglu- tinating reaction with cultures "I" the bacillus lepi a fact which goes to prove thai the organism culti- vated is the true cause of the disease with which it is associated. Pathogenesis. — Some investigators claim to ha had positive results in Inoculation experiments on animals with portions of leprous tubercles, excised for the purpose; Dul none has succeeded in producing the typical lesions of the disease a- tmi in man. Arning inoculated a condemned criminal in the Sandwich Islands with fresh leprous tubercles, bis death occur- ring from leprosy five year-, later; bul there i- no con- clusive evidence of the transmissibility of the di in this way, as tin- man, according to .Swift, had oilier opportunities for becoming infected. It is generally assumed that infection takes place through the mucous membranes ami through slight skin wounds. There is said to be no infect ion by way of the digestive tract. With regard to the question of direct inheritance from the mother to the unborn babe, there is considerable difference of opinion. Some cases of intrauterine infection have been repor led but they are at least very rare. Leprosy bacilli are frequently present in the spermatic fluid and in the milk, but they have never been found in the ovaries. Most commonly they are met with in purulent nasal secretions (one hundred and twenty-eight out of one hundred and fifty-three cases examined by Sticker), and in the mucous membranes of the mouth, throat, etc.; but they have also been found in various other organs of the body, in the nerves, and in the blood. The widespread opinion, which was held before the dis- covery of the leprosy bacillus, that the disease was associated in some way with the eating of certain kinds of food, as salt fish, has now been generally abandoned. The negative results obtained from inoculation experiments, together with the fact that infection is not readily transmitted to persons exposed to the disease, have been explained by the assumption that the bacilli contained in the leprous tissue are mostly dead and non-virulent; but it is much more probable that a special susceptibility to the disease, inherited or acquired, is requisite for its production. The great similarity in many respects of leprosy to tuberculosis has recently been still more emphasized by the observations of Babes and Kalindero, who state that leprosy reacts, both locally and generally, to an injection of tuberculin in the same manner as tuberculosis. The Smegma Bacillus (Bacillus srnegmatis). — Found by Tavel and Matterstock in the smegma pra?putii, between the scrotum and thigh, and between the labia; also in the cerumen and occasionally on the skin. The bacilli lie in clusters either in or between the epithelial cells, the rods being very similar, in size and form, to those of the tubercle bacilli. They stain with difficulty, and resist decolorization with acid when stained by the methods for staining the tubercle bacillus, but are decolorized when treated for one minute with absolute alcohol. This bacillus is most likely to be mistaken for the tubercle bacillus in the examination of urine. Lustgartex's Bacillus. — This organism, which very closely resembles the tubercle bacillus, was found by Lustgarten (1SS4) in the secretions of syphilitic ulcers and believed by him to be the specific cause of syphilis. Doutrelepont about the same time also observed a similar organism and came to a like conclusion. It has since been shown that in nor- mal smegma, bacilli are found in great abundance similar in their morphology to the bacillus of Lustgar- ten, but differing, as a rule, in certain staining peculiarities. Lustgarten's bacillus stains with equal difficulty as S43 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES the tubercle bacillus, but is much less resistant to the action of acids; it is also more resistant, as a rule, to the decolorizing action of alcohol than is the smegma bacillus. Numerous attempts have been made to cultivate this bacillus artificially but without success. The inoculation of animals with syphilitic tissues and secre- tions has also given only negative results, though in man, as is well known, infection by inoculation fre- quently takes place, the tertiary lesions only being non-infectious. Lustgarten's bacillus has been found in various syphilitic tissues, in beginning sclerosis, in the papules, in condylomata and gummata, and not only in the vicinity of the genitals, but also in the mouth, throat, heart, and brain. No satisfactory experimental evi- dence has been given, however, of its causative rela- tion to syphilis. It is now recognized that Trep- onema pallidum (spirochata pallida), discovered by Sehaudinn and Hoffman, in 1905, is the specific cause of syphilis. The Influenza Bacillus (Bacillus influenza'). — Discovered by Pfeiffer and isolated in pure cultures (1S91-92) from the purulent bronchial secretion^ of patients suffering from epidemic influenza. Pfeiffer's discovery has been fully confirmed by others, the results of whose researches give us reason to believe that this bacillus is the chief etiological factor in the production of influenza or "la grippe." Microscopical Appearances. — Extremely small, mod- erately thick bacilli, about two or three times as long as broad, with rounded ends, occurring singly or in pairs, but threads or chains of three or four elements are occasionally met with in cultures; often found in the interior of cells. (See Plate VIII., Fig. 3.) Motility. — Non-motile. Spore Formation. — Does not form spores. Staining Reactions. — The influenza bacillus stains with difficulty with the ordinary aniline colors; best with dilute ZiehFs solution of carbol fuchsin or Loeffler's methylene blue solution, with heat. When faintly stained the two ends of the bacilli are somewhat more deeply stained than the middle portion. It does not usually stain with Gram's solution, though some investigators report such staining reaction. Biological Characters. — Strictly aerobic; no growth occurs below 26° C, or above 43° C, or in the entire absence of oxygen; optimum temperature, 37° C. Grows on the surface of solid nutrient media contain- ing hemoglobin or pus cells, as blood agar or blood se- rum. At the end of eighteen to twenty-four hours on such culture media in the incubator very small, drop- like colonies are developed, which under a low mag- nification appear as shining, transparent, homogene- ous masses; older cultures are sometimes colored yellowish brown in the center. A characteristic feature of the growth of the influenza bacillus is that the colonies tend to remain separate, although when thickly sown in a film of moist blood upon nutri- ent agar they may occasionally become confluent. Spread out in a thin layer upon the surface of blood bouillon the growth develops as delicate white flakes. According to Grassberger a mixture of nutrient agar and defibrinated blood, which has been kept for one hour at 50° to 60° C, makes an especially good soil for their growth. Vitality. — The influenza bacillus is very sensitive to desiccation; a pure culture diluted with water ami dried is destroyed with certainty within twenty-four hours. In dried sputum vitality is retained for from twelve to twenty-four hours, according to the degree of drying. It does not grow, but soon dies in water. The thermal death point is 60° C. with five minutes' exposure. In bouillon cultures at 20° C. the bacilli remain alive for from a few days to two or three weeks. Pathogenesis. — The bacillus of influenza, so far a-; is known, produces the disease by artificial infection only 844 in monkeys and rabbits. From numerous experi- ments made in guinea-pigs, rats, mice, and pigeons these animals seem to be immune to influenza. When a small quantity of a twenty-four-hour-old culture on blood agar is injected intravenously into rabbits Pfeiffer found that a characteristic pathogenic effect was produced. Within one and one-half to two hours after the infection, the animals became very feeble and suffered from dyspnea, the temperature rising to 41° C. or more. At the end of five or six days they were able to sit up and move about again, and later they recovered. Larger doses caused death. When cultures were rubbed into the nasal mucous mem- branes of monkeys, these animals showed a febrile condition, lasting for a few days, but in no instance has Pfeiffer observed a multiplication of the bacilli introduced, the results being due to toxic products. Cantani has shown that it is possible to produce an infection of influenza in rabbits when inoculated with small doses (0.25 to 0.5 c.c.) of living bacilli, provided the point of least resistance is chosen, viz., the brain, the toxic products of the influenza bacillus acting most powerfully upon the central nervous system. The cell bodies of the bacilli seem to posse- considerable pyogenic action. It is possible that an immunity against the influenza poison lasting for a short period may be established after an attack. At least in three experiments made by Pfeiffer on monkeys, these animals, after recover- ing from an inoculation, seemed to be less susceptible to a second injection. The influenza bacillus has not been found outside of the body. In patients suffering from influenza the bacilli are chiefly met with in the nasal and bronchial secretions more especially in the characteristic light yellowish to green purulent sputum. The older the process the fewer bacilli will be found, and the more frequently will they be seen lying within the pus cell?. At this time they stain less readily and present more irregular and swollen forms. Very often, perhaps almost invariably, the process invades portions of the lung tissue. In severe cases a kind of lobular pneu- monia results, and is accompanied by symptoms almost identical with bronchopneumonia. In fatal cases the bacilli have been found to have penetrated not only into the peribronchial tissue, but even to the surface of the pleura. The pleurisy which follows in- fluenza, however, is usually a secondary infection, due to the streptococcus or pneumococcus. Ordinarily the disease runs an acute or subacute course, and not infrequently it is associated with a mixed infection of the pneumococcus or streptococcus. But sometimes a chronic condition may be produced depending upon the influenza bacillus; the bacilli remaining latent for a while and then becoming active again, with a resulting exacerbation of the disease. Phthisical patients are particularly susceptible to attacks of influenza. It would appear, therefore, that given proper climatic conditions, we have at all times the seeds of influenza present in sufficient numbers to start an epidemic. The discovery of this bacillus enables us to explain many things previously unaccountable in the cause of epidemic influenza. We now know from the fact that the bacillus cannot exist for any considerable length of time in water or in dust, that the disease is not trans- missible to great distances through these means. We also know that the infective material is contained chiefly in the catarrhal secretions. The occurrence of sporadic cases, or the sudden eruption of an epidemic in a locality from which the disease has been long ab- sent, and where there has been no new importation of infection, may possibly be explained by the supposi- tion, as already noted, that the influenza bacilli re- main latent in the air passages of certain individuals for months at a time, and then become active under conditions favorable for their growth, when the in- fection mav be communicated to others in close con- REFERENCE IIAXDHooK OF THE MEDICAL SCIENCES i: i. i. 1 1. 1 tart with them. The bacteriological diagnosis of in- fluenza is of considerable importance for the identifi- i, of clinically doubtful cases, which from the symptoms may be mistaken for other diseases, such, as bronchitis, pneumonia, or tuberculosis. In acute uncomplicated cases the probable diag- nosis can be frequently made by microscopical nination of stained preparations of the sputum, there being present enormous numbers of the small bacilli. In chronic cases or those of mixed infection the culture method must usually be employed if we wish to arrive at positive results. The bacillus of influenza is so well characterized by its morphological, staining, and cultural peculiarities that it may be distinguished from all other bacteria by an expert bacteriologist with sufficient certainty for diagnostic purposes. The only bacillus which at all closely resembles it is the pseudo-influenza bacillus found by Pfeiffer in three cases of bronchopneumonia; and this is distinguished from the genuine influenza lus by its larger size and tendency to grow out, iu cultures on blood agar, into long threads. The Koch-Weeks Bacillus op Conjunctivitis. — This bacillus was first observed by Koch in 1883, later, in 1887, it was specifically described by Weeks, who obtained it in pure cultures. The infective disease, of which it is the cause, seems to be widely distributed, no land or clime being exempt from it. In this country it occurs epidemically during the spring and fall months. It is known commonly as "pink eye." Motility. — Non-motile. Spore-Formation. — Absent; in culture media the bacilli die rapidly, seldom living more than five days. They resist a temperature of 50° for ten minutes. They cannot resist drying for any length of time. Morphology. — The "bacilli from the purulent secre- tion are small and slender, being not unlike the influenza bacilli but somewhat longer. The shorter bacilli not infrequently have the appearance of diplococci and sometimes they exhibit polar staining. Their width is constant. The ends are rounded. They are rapidly decolorized by Gram. Staining. — They are best stained by dilute solutions of carbol fuchsin or Loeffler's methylene blue, but do not stain readily. In smear preparations the Koch- Weeks bacilli are, as a rule, seen alone or associated with isolated cocci and bacilli within the cells, and are very rarely associated with gonococci and pneu- mococci, such mixed infections being very uncommon. Biological Characters. — The Koch-Weeks bacillus grows only at temperatures near to 37° C. of the ordinary culture media. None but moist and slightly alkaline peptone agar can be employed. The best results have been obtained with serum agar or a mix- ture of glycerin agar and ascitic fluid, 2 to 1. Pure cultures are rarely obtained at first, being usually associated with colonies of xerosis bacilli or staphylo- cocci. After twenty-four to forty-eight hours the colo- nies are noticeable as moist, transparent, shining drops. Microscopically examined under low power they ap- pear like small gas bubbles; on closer examination they are seen to be round, lying loosely on the surface, and are readily removed. Under higher power a number of fine points are observable. The colonies resemble t hese of influenza, have a tendency to confluesce, but are not so sharply defined as the latter and become more quickly indistinguishable. In serum or blood bouillon a slight cloudiness is produced which finally settles down. Pathogenesis. — The Koch-Weeks bacillus is not pathogenic for animals. Man, on the contrary, is extremely susceptible to infection. Transmission of the disease occurs only by contact either by direct or indirect conveyance of the moist infective material. Infection is not communicated through the air by ans of dust, as the bacilli soon die when dried. it may, however, be conveyed by flies, etc. Im- munity is not produce, 1 to any extent by i attack, but there doe i seem to bi i dual susceptibility. The only mic-roc, i from which the Koch- Weeks bacillus would seem to require differentiation are those of the influenza group. These latter bacilli, however, grow well only on hemoglobin media, which the Koch-Wi I iculus does not require. The colonies on ,-ei uin agar are also .-mailer than those of the influenza bacilli and thi more granular. The Diphtheria Bacilli dipht) Klebs-Loeffler b -This bacillus was first ol erved by Klebs (1883) in diphtheritic false membrane. Ii ated in pure cultures and its pathogenic properties demonstrated by Loeffler in L884. In lss7 ss further studies by Loeffler, Roux, an,l Yer-in added to the proof of the dependence of diphtheria upon this bacillus. The results of thi investigations have since been confirmed by a gri number of combined clinical and bacteriological observations both in animals and man. All the conditions have been fulfilled for diphtheria which are necessary to the most vigorous proof of the causative relation of a given microorganism to an infectious disease, viz., the constant presence of the organism in the lesions of the disease, the isolation of it in pure culture, the failure to produce the disease by any other bacteria, and the additional demonstration (if the immunizing value of the specific antitoxic sub- stances developed in animals subjected to injections of diphtheria toxin. In view of these facts we are justified in concluding that all cases of U-iir or primary diphtheria are due to the Klebs-Loeffler bacillus. Microscopical .1 /ipcaranccs. — .Somewhat slender rods of variable size, 1 to 6 /i long and 0.3 to 0.8 ». broad, either straight or slightly curved, with rounded ends, occurring singly or in pairs. Irregular forms are very common, and indeed are characteristic of this bacillus. In the same culture and in unfavorable media great differences in form and dimensions occur; one or both ends may appear swollen, or the central portion may be thicker than the extremities, or the rod may consist of irregular spherical or ovoid seg- ments. The rods sometimes lie in clusters alongside of one another in a characteristic manner, like a bundle of fagots. Threads with swollen ends and branching forms sometimes occur, but these are com- paratively rare. (See Plate VIII., Fig. 4.) Motility. — Non-motile. Spore Formation. — Absent, but cultures retain their vitality for months. Staining Reactions. — Stain readily with the ordinary aniline dyes and retain fairly well their color after staining by Gram's method. When Loeffler's alkaline solution of methylene blue is applied cold for five minutes or warm for one minute, the bacilli, from blood-serum cultures especially and from other media less constantly, stain in an irregular and extremely characteristic way. Carbol fuchsin and gentian violet stain the bacilli too intensely, obscuring the struc- ture of the organisms. Neisser has recently described a double stain which brings out the metachromatic bodies of the diphtheria bacillus, and which he claims may be used as a method of differential diagnosis between the virulent and non- virulent diphtheria bacilli without the delay of in- oculating animals. The cover-slip smear of diphtheria bacilli is placed for two or three seconds in a solution composed of alcohol (96 per cent.) 20 parts, methylene blue 1 part, acetic acid (glacial) 50 parts, and distilled water 950 parts, and then, after washing, in a second solution (for from three to five seconds) composed of Bismarck brown 1 part, and boiling distilled water 845 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES 500 parts. By this method the bacilli are usually stained brown and at one or both ends a blue granule is seen; while the non- virulent bacilli ordinarily are not so stained. But sometimes the pseudodiphtheria bacilli show the same dark bodies, and occasionally the virulent bacilli fail to take the Neisser stain. Neither this nor any other stain, therefore, can be depended upon to give positive information as to the virulence of the bacilli, the only certain way of obtaining a differential diagnosis between the pseudo- and true diphtheria bacilli being by animal inocula- tions with control injections of antitoxin. (See Plate VIII, Fig. 5.) Biological Characters. — Aerobic and facultative anaerobic; grows best in the presence of oxygen, but also less readily without it. Development is good and abundant only at 37° C, the extremes being 20° and 41° C. It grows on all the ordinary culture media, glycerin agar being a favorable medium, though blood serum and ascitic fluid are still better. Loeiller's blood-serum mixture (see Bacteriological Technique) is much used and is the best culture medium for diagnostic purposes in examining cul- tures from the throats of persons suspected of having diphtheria. The growth in gelatin at 22° to 24° C. is not characteristic, and is so scanty that it is seldom employed for the cultivation of the diphtheria ba- cillus. The gelatin is not liquefied. Growth on Blood Serum. — On Loeffler's blood- serum mixture at the end of eight to twelve hours small colonies develop which appear as pearl gray, or more rarely yellowish gray, slightly elevated points. The borders are usually uneven. After forty-eight hours the colonies when separated may so increase in size that they are one-eighth of an inch in diameter; these lying close together become confluent and fuse into one mass, if the serum be moist. During the first twelve hours the colonies of the diphtheria bacilli are about equal in size to those of other pathogenic bacteria which are often present in the throat; but after this time the diphtheria colonies become larger than those of the streptococci and smaller than those of the staphylococci. The blood serum is not liquefied. Growth on Agar. — On one per cent, slightly alkaline, nutrient or glycerin agar the growth of the diphtheria bacillus is less certain and luxuriant than upon blood serum, but the appearance of the colonies when ex- amined under a low-power lens is often more charac- teristic; the growth, however, is variable, and when obtained fresh from pseudo-membranes the colonies develop slowly or fail to develop at all. On agar plates the deep colonies are usually round or oval and as a rule present no extensions, but the surface colonies commonly from one and sometimes from both sides spread out an apron-like extension which exceeds in area the rest of the colony. These surface colonies are more or less coarsely granular in structure and usually have a dark center. Some are almost trans- lucent, others are thick and luxuriant with irregular borders shading off into a delicate lace-like fringe, though sometimes the margins are more even and the colonies are nearly circular. With a high-power lens the edges show sprouting bacilli, the colonies being gray or grayish white by reflected light and pure gray with olive tint by transmitted light. A mixture com- posed of two parts of a one and one-half per cent, nutrient agar and one part of sterile ascitic fluid makes a medium upon which the bacillus grows much more luxuriantly but not so characteristically. Nut- rient plain or glycerin agar, with or without the addi- tion of ascitic fluid, is the medium employed for the isolation of the diptheria bacillus by plate methods from the original serum tube. The agar should be freshly melted and poured into the Petri dish for this purpose, and after it has hardened streak cultures from the colo- nies on blood serum are made upon this, the plates 846 being left in the incubator at 37° C. for twelve hours. Growth on Gelatin. — The growth on gelatin is much slower and more scanty than that on blood serum or agar, on account of the lower temperature at which it is used. Gelatin is not liquefied. Growth in Bouillon. — In slightly alkaline or neutral bouillon the diphtheria bacillus grows in fine grains which are deposited along the sides and on the bottom of the tube, leaving the broth nearly clear. Some- times the bouillon may appear diffusely clouded to the naked eye, but when examined microscopically in the hanging drop the clumpy arrangement is readily observed. Frequently a whitish film forms over part of the surface, but in shaking this breaks up and slowly sinks to the bottom. This film is more apt to develop in cultures which have been long cultivated in bouillon. The reaction of the bouillon is subject to changes — the diphtheria bacillus in its growth causes a fermentation of the meat sugars with the production of acid; hence the bouillon becomes at first acid and subsequently alkaline, when the fermentable sugars have been decomposed this latter change being favored by the admission of air. Growth in Milk. — The diphtheria bacillus grows readily in milk, beginning to develop at a compara- tively low temperature (20° C). Thus milk having become inoculated with the bacillus from a case of diphtheria may under certain circumstances be the means of conveying infection to previously healthy persons. The growth takes place better in raw than in boiled milk. The milk is not coagulated, remaining unchanged in appearance, but the cultures may retain their vitality for a long time. On potato which is rendered alkaline a delicate coating develops. Vitality. — Virulent diphtheria bacilli may persist in the throats of convalescents from diphtheria, after the disappearance of the false membrane, for weeks and months even. In 304 of 005 consecutive cases of diphtheria examined by Park and Beebe the bacilli were found to be no longer present within three days after the disappearance of the false membrane; in 176 cases they persisted for seven days, in 64 cases for twelve days, in 36 cases for fifteen days, in 12 cases for three weeks, in 4 cases for four weeks, in 2 cases for nine weeks, and recently a case has been noted in which the virulent bacilli were present for eight months. The practical importance of this fact is the evident necessity for the isolation of convalescents from diphtheria, whether showing clinical symptoms or not, until all the Klebs-Loeffler bacilli have dis- appeared from the throat. In cultures kept in a cool, dark place, the bacilli retain their vitality for from six months to a year or more. In the incubator they are generally killed by desiccation in from one to three months; but even here, when the air is excluded, they remain alive in bouillon for a long time. They also retain their vitality for a considerable time in water and articles of food, etc. The diphtheria bacillus possesses a considerable re- sistance to desiccation. Pure cultures in saturated silk threads at room temperature remain alive under favorable conditions for months. In dried diphther- itic exudate, even when pulverized, they retain their virulence for a long time. They are soon killed by moist heat at 60° C. Cold has comparatively little influence upon them, and even when dried they retain their virulence in winter for several months. Sus- pended in water and exposed to the action of direct sunlight the bacilli die in a few hours, but in agar and bouillon cultures they remain alive for six hours. Chemical Effects. — The diphtheria bacilli produce gas and acids from carbohydrates, as from glucose present in ordinary nutrient bouillon. They also REFERENCE HANDBOOK OF THE MEDICAL SCIENt ES Bacteria oduce sulphurated hydrogen ami indol. In old Itures some nitrites are present, which with the dol give the nitroso-indol reaction on the addition pure sulphuric acid. Pigment production is rare, ough occasionally yellow to reddish species have in met with. Old bouillon cultures of the diph- eria bacillus filtered through porcelain produce the me symptoms as inoculations with t he bacilli t hem- Ivcs. Particularly active toxins are obtained, cording to von Dungern, by the addition of ascitic lid to the bouillon. Sugar is to be avoided. Bouil- n cultures as long as they are acid contain no toxins. two per cent, peptone nutrient bouillon, having an kalinity equal to about 8 c.c. of normal soda solu- .iii per liter above the neutral point to litmus, is a litable medium for the development, of toxin. Free cess of air favors its production. The greatest umulation of toxin in bouillon is after a growth of urn five to ten days in the incubator at 35° to 37° C. These poisons of diphtheria have been partially olatcd. They are precipitated in part by alcohol, ilcium phosphate, calcium chloride, and magnesium ilphate. The toxin has not yet been successfully tialyzed, so that its chemical nature is unknown. It as many of the properties of protein substances, but is formed not only in albuminous culture media ut also in those free from albumin. It is not a table body, being totally destroyed by boiling for ve minutes, and losing ninety-five per cent, of its i rength when exposed to a temperature of 75° C. for oine time. Temperatures under 60° C. alter it only ery gradually. It is slowly decomposed when ex- losed to light and air, but kept in a cold, dark place it nay be preserved almost indefinitely. According o Kossel diphtheria toxin is formed in the cell bodies if the bacilli and thence secreted. Ehrlich, sub- livides toxins, according to their degrees of toxicity, nto protoxoids, syntoxoids, and epitoxoids. Pathogenesis. — The diphtheria bacillus is patho- ;enic for guinea-pigs, rabbits, chickens, pigeons, small jirds, and cats; also in a lesser degree for dogs, goats, •attle, and horses, but scarcely at all for rats and mice. True diphtheria, however, as observed in man, is ■xtremely rare among these animals, the so-called iiphtheritic inflammations in them being due, as a rule, to other bacteria than the Klebs-Loeffler bacillus. The virulence of pure cultures of the diphtheria bacillus from different sources, as measured by their toxin production, varies enormously. In general, severe cases of diphtheria yield strongly virulent cultures, and mild cases slightly virulent ones; but there are exceptions to this rule. One of the most, virulent cultures so far known — culture No. 8, which is used not only by the New York Health Department Laboratory, but by many other laboratories in the United States and Europe, for the production of toxin — was obtained from an extremely mild case of diph- theria. Experimental and accidental attenuation of the diphtheria bacilli has often been observed. Roux and Yersin maintain that there is a uniform and gradual decrease in virulence of the bacilli found in the throats of convalescents from diphtheria, but this has not been confirmed by others, highly virulent bacilli having been repeatedly found in the throats of those recovering from the disease long after the disap- pearance of all clinical symptoms. The same marked variation occurs in the amount of toxin produced by different bacilli in their growth in media outside of the body. There are also bacilli which produce no specific toxin whatever and yet appear to have all the other characteristics of virulent bacilli. Moreover, some diphtheria bacilli retain their virulence, when grown in artificial media, much longer than others. The passage of the bacilli through the bodies of suscep- tible animals does not increase their virulence to any appreciable extent, this being probably due to the fact that they multiply but little in thi !' The best guide for the virulence of a diphtheria bacillus is the toxicity of the lilt rate of a culture of defi- nite age, as shown by inoculation Into guinea-pig for tin purpo e an alkaline broth culture of forty-eight hours' growth is used. The amount injected should not be more than one-fifth per cent, of the body weight of the animal inoculated, unless controls with antitoxin are made. In the large majority oi ca i , when the bacilli are virulent, thi a urn causes death within seventy-two hours. For an absolute test of specific virulence antitoxin must be used. A guinea- pig is injected subcutaneously with antitoxin, and then this and a control animal are injected with double the fatal dose of a broth culture of the bacilli to be tested. If the animal which received the anti- toxin lives, while the control animal dies, it was surely a virulent diphtheria bacillus which killed by means of the toxin produced. About twenty-four hours after the subcutaneous inoculation of a virulent culture of the diphtheria bacillus the animal becomes languid, has no appetite, its hair is rumpled, its nose cold and blue, and its respiration rough; the point of injection is infiltrated, sometimes also the surrounding tissues. Certain symptoms, however, exclusive of Toss of weight, may be wanting. On autopsy there will be found at the seat of inoculation a grayish deposit surrounded by an area of congestion; the subcutaneous tissues for some distance around are edematous; the adjacent lymphatics are swollen, and the serous cavities, especially the pleural and the pericardial, frequently contain an excess of fluid, usually clear, but at times turbid; the lungs are generally congested. In the organs are found numerous smaller or larger masses of necrotic cells, which are permeated with leucocytes. The heart and voluntary muscular fibers usually show degenerative changes. Occasionally there is fatty degeneration of the liver and kidneys. From the area surrounding the point of inoculation virulent bacilli may be obtained, but in the organs they are only occasionally found, unless an enormous number of bacilli have been injected. Paralyses, commencing generally in the posterior extremities and gradually extending to other portions of the body and causing death by cardiac paralysis or paralysis of the respira- tory organs, are also produced in many cases in which the inoculated animals do not succumb to a too rapid intoxication. In rare instances the muscles of the neck or of the larynx are first paralyzed and thus characteristic symptoms are produced. Rabbits are much less susceptible to subcutaneous inoculation than guinea-pigs; white mice and rats are almost immune. On the other hand, cats, dogs, cows, and horses are susceptible, as are also young pigeons and chickens, and small birds. Diphtheritic false membrane, analogous to human diphtheria, may be produced in animals by rubbing diphtheria bacilli on the slightly abraded surface of mucous membranes of the trachea and conjunctiva of rabbits, of the throats of monkeys, and of the pharynx and larynx of pigeons and chickens. The process remains local. According to Loeffler, the best results are obtained by inoculation of the vagi- nal mucous membranes of guinea-pigs. In man no experimental inoculations have been made but in two involuntary laboratory experiments made in the New York City Health Department severe diphtheria was contracted by inadvertently sucking up virulent bouillon cultures of the diphtheria bac- illus into the mouth. Outside of the body diphtheria bacilli have been found upon articles used by diphtheria patients, as upon linen, brushes, toys, walls and floors of rooms, etc., and in the hair of nurses. The air (exclusive of momentary contamination through the coughing of 847 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES patients) never contains the bacilli. They have also been found at times in the throat and nasal cavities as well as in the conjunctiva of healthy individuals, especially of those coming in contact with diphtheria patients. Out of three hundred and thirty healthy persons who had not been in contact, so far as known, with cases of diphtheria, Park and Beebe found viru- lent bacilli in eight only, two of whom later developed the disease. It is evident, therefore, that infection from diphtheria, as in other infectious diseases re- quires not only the presence of virulent bacilli in the throat, but also an individual susceptibility at the time to the disease. Among the predisposihg factors which may contribute to the production of diphtheria are the breathing of foul air and living in overcrowded and ill-ventilated rooms, poor food, and certain other affections more especially catarrhal inflammations of the mucous membranes, but all depressing conditions in general favor the development of the disease. The chief locations of the bacilli in diphtheria are on the surface of the pseudomembranous inflammations of the fauces, larynx, and nasal cavities, but also occa- sionally in membranous affections of the skin, vagina, rectum, conjunctiva, nose, and ear (membranous rhinitis and otitis media). Occasionally they have been found in the blood and interior organs (spleen and kidneys). Almost always the streptococcus pyogenes is asso- ciated with the diphtheria bacillus, with which it acts pathologically as a synergist. Regarding the im- portance of mixed infection in diphtheria, Bernheim has stated that the streptococcus products of decom- position favor the growth of the diphtheria bacilli and increase their virulence for production of toxin. Nevertheless, the diphtheria bacillus alone undoubt- edly may produce all the clinical symptoms of sepsis. Xiin-rirulent Diphtheria Bacilli. — There are some- times found in inflamed throats as well as in healthy throats, either alone or associated with virulent diphtheria bacilli, microorganisms which though morphologically and biologically identical with the Klebs-Loelller bacillus appear to be non-virulent — that is, in artificial culture media and with the usual animal tests they produce no appreciable diphtheria toxin. Between the bacilli which produce a great deal of toxin and those which seem to produce none at all we find all grades of virulence. These are prob- ably attenuated varieties of the diphtheria bacillus which have lost their power of producing toxin (Roux and Yersin). Bacilli are also found which resemble the Klebs-Loeffler bacilli very closely except in toxin production, but differ also in some other respects. From varieties of this kind having been found in a number of cases of so-called xerosis con- junctives these bacilli are often designated as xerosis bacilli. They are usually much larger than diphtheria bacilli and have club-like extremities. They may be almost non-pathogenic for guinea-pigs, or they may kill. Animals are not protected by diphtheria anti- toxin from the action of these bacilli. Whether they are derived from the original diphtheria stock is not known. Pseudodiphtheria Bacilli. — Besides the typical bacilli which produce diphtheria toxin and those which do not, but which, so far as we can determine, are otherwise identical with the Loeffler bacillus, there are other bacilli found in positions similar to those in which diphtheria bacilli occur, and yet, though re- sembling these organisms in many particulars, differ from them in certain important characteristics. .The variety most prevalent is rather short, plump, and more uniform in size and shape than the true Loeffler bacillus, and the great majority of them in culture show no polar granules when stained by the Neisser method, staining evenly throughout with Loeffler's alkaline methylene blue solution. Their . colony growth on blood serum is very similar to that of the SIS diphtheria bacilli, but they do not produce acid by the fermentation of glucose, and they never produce diphtheria toxin. These are called pseudodiphtheria bacilli, or more properly, B. hofmani. When found in cultures from cases of suspected diphtheria they may lead to an incorrect diagnosis; and here the Neisser method of staining is of value, though the only absolute test of virulence is by inoculation or sus- ceptible animals. (See Plate VIII., Fig. 6.) Pseudomembranous Inflammations due to Bacti ri,i other than the Diphtheria Bacilli. — The diphtheria bacillus, though the most usual, is not the only micro- organism that is capable of producing pseudomem- branous inflammations. The streptococcus, staphylo- coccus, and pneumococcus are the forms most often found in angina simulating diphtheria, but there are also others which, under suitable conditions, take an active part in producing this kind of inflammation. But the bacteria which occur in this so-called false diphtheria are all morphologically and culturally distinct from the Loeffler bacilli. Susceptibility and Immunity. — It is now commonly recognized that an individual susceptibility, both general and local, to diphtheria is necessary to con- tract the disease. Age has long been known to be an important factor in the production of diphtheria, children within the first six months of life being but little susceptible, most so between the third and tenth years, while adults are comparatively immune. An apparent inherited susceptibility to the disease has also been observed. Two attacks of diphtheria have rarely been known to occur in the same individual within a short time. But to what this natural sus- susceptibility or immunity is due is as yet only par- t ially understood. As the result of animal experiment b, however, it has recently been shown that an artificial immunity against diphtheria can be produced, at least for a considerable period, by the development, in the body, of substances antidotal to the diphtheria toxin. Animals may be immunized against the diphtheria bacillus in various ways: By treatment first with slightly virulent and then with highly virulent cultures of the bacillus; by injection of small quantities of attenuated cultures or of toxin, and then with gradu- ally increasing doses; by injection of the blood serum of animals immunized in one of the above ways against diphtheria. In the earlier experiments on immunization against diphtheria the names of Fraenkel, Wernicke, Aronson, Roux, and others are conspicuous; but to Behring and Kitasato belongs the credit of the fundamental discovery that the blood serum of an animal immunized for certain infec- tious diseases may be employed for protective inocu- lations, and that in larger quantity it may even exer- cise a curative influence after infection has occurred. This is one of the greatest discoveries in scientific medicine of recent years, and the practical results obtained in the treatment of diphtheria, at least, have justified all the expectations that were enter- tained regarding it. The mortality of this fatal malady among children has been reduced fifty per cent, or more in places where diphtheria was prevalent and where the treatment was continuously and uni- formly employed. As to immunity, it stands to reason that a disease which can attack the same person more than once within a comparatively short time does not belong to the class of affections producing a permanent immunity after recovery. It is, however, well known that a certain temporary immunity is thus conferred, and the blood serum of persons during convalescence from diphtheria has been found to possess immunizing properties. The protection afforded by artificial immunization, therefore, does not last usually more than three or four weeks, but this is usually sufficient to tide over the period of exposure to infection, and if necessary repeated immunizing injections of the EXPLANATION OF PLATE VIII. EXPLANATION OF PLATE VIII. Fig. 1. — Bacillus Tuberculosis in Sputum. X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Piq, 2. — Bacillus of Leprosy, Section of Skin Nodule. X 1,000. Photomicrograph from Bowhill's "Bacteriology" by permission. Fig. 3. — Bacillus of Influenza in Bronchial Mucus. X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. 4. — Bacillus of Diphtheria (Klebs-Loeffler). Blood-serm culture stained with Loeffler's solution of methylene blue. X 1,000. Photomicrograph from Sternberg's "Bacteri- ology" by permission. Fig. 5. — Bacillus of Diphtheria. Stained with Neisser's solution, showing bodies of bacilli in smear faint brown; points, dark blue. X 1,000. Photomicrograph from Park's "Bacteriology" by permission. Fig. 6. — Pseudo-Diphtheria Bacillus, Small Type. X 1,000. Photomicrograph from Park's " Bacteriology" by permission. Fig. 7. — Bacillus of Typhoid Fever, from Agar Culture. X 1,000. Photomicrograph from Sternberg's "Bacteriology" by permission. Fig. S. — Bacillus of Typhoid Fever with Flagella. Agar culture. X 1,000. Photomicro- graph from BowhUl's "Bacteriology" by permission. Reference Handbook of THE Medical Sciences Plate VIII ** I. Tubercle Bacilli in Sputum. Vv V VI 4 "-,vj'-.V '!• t- > Pseudo-diphtheria Bacillus, i Small Type). '<: f » » A"' V , > - / ' » fl .V//7 Diphtheria Bacillus. V?* , »»* *' *| ' I Blood-serum Loefllers Meth- " • »V > **' , -f , * ^ ,/«J VN ylene-blue stain). / y t • - « Nl>f &"' *'•. e ■ .,?■■ •• >- •r- •• a. Leprosy Bacillus. • ' • -.- - • ••■• ' - . -.• • • v.f 1 ^ v.* VII. -.-*■? ■-.' .. .;»»- Bacillus of Typhoid Fever. Diphtheria Bacillus. (Ncisscr Stain). III. Influenza Bacillus. Pathogenic Bacteria. VIII. Bacillus of Typhoid Fever with Flagella. REFERENCE HAN'DRooK OK THE MEDICAL SCIENCES Bacteria ntitoxic serum may bo given. Regarding the cura- ivc injections, the earlier the remedy is administered !»■ more certain and rapid is the effect produced his effect being, indeed, one of immunity or protection gainst further infection or absorption by the system if the diphtheria toxin, rather than of neutralization ,f the poisons already absorbed. Preparation of Diphtheria Antitoxin. — The principal teps in the preparation of diphtheria antitoxic serum the production of toxin, the immunization of the lorses, and the testing of the antitoxin obtained from ii. The following is the met hud in brief now mployed in the laboratories of the Health Depart- ment of New York City: The strongest diphtheria oxin possible is obtained by taking a very virulent laciilus and growing it under the conditions already ribed. The culture, after a week's growth, is emoved, and having been tested for purity is rendered terile by the addition of ten per cent, of a five per ent. solution of carbolic acid. This sterile culture is hen tillered through ordinary sterile filter paper and lured in full bottles in a cold place until needed, ts strength is tested by giving a series of guinea-pigs fully measured amounts injected subcutaneously. .ess than 0.01 c.c., administered hypodermatically, hould kill a 250 gm. guinea-pig. The horses used or immunization should be young and absolutely lealthy. A number of such animals are severally ejected with an amount of toxin sufficient to kill i,000 guinea-pigs of 250 gm. weight (about 20 c.c. of trong toxin), the point of injection being usually inder the skin of the neck or behind the shoulder. \ftcr an interval of from three to five days, so soon is the febrile reaction has subsided, a second sub- cutaneous injection of a slightly larger dose is given. With the first three injections of toxin 10,000 units of mtitoxin are administered. If antitoxin is not nixed with the toxin only one-tenth of the doses ibove mentioned is to be given. At the end of about wo months, increasing doses of pure toxin having jeen injected every five to eight days, from ten to wenty times the original amount is administered. ii about three months the antitoxic serum drawn rom the horses should contain at least 300 antitoxin tnits, when tested, and the best of them from 800 to 1,000 units, in each cubic centimeter. Very few lorses ever yield over 1,000 units, and none so far has ;iven as much as 2,000 units per cubic centimeter. (f every nine months an interval of three months' reedom from inoculations is given, the best horses ■ontinue to furnish high-grade serum during their leriods of treatment from two to four years. In order to obtain the serum the blood is withdrawn 'rom, the jugular vein by means of a sharp-pointed "annula, which is plunged through the vein wall, a slit laving been made in the skin. It is run into large flasks through a sterile rubber tube, and then allowed to clot, the flasks having been previously placed in a slanting position. From these the serum is drawn off after four days by means of sterile glass and rubber tubing, ind is stored in large bottles, small vials being filled is needed for use. Every possible precaution should, of course, be taken in the preparation of the serum to avoid contamination. An antiseptic may be added to the serum as a preservative, but it is not ordinarily necessary. Kept from access of air and light and in a cold place, it is fairly stable, deteriorating not more than thirty per cent., and often much less, within a year. When stored in vials and kept as above, diph- theria antitoxin continues within ten per cent, of its original strength for at least two months; after that it can be used by allowing for a maximum de- terioration of two per cent, for each month. Diphtheria antitoxin has the power of neutralizing diphtheria toxin, so that when a certain amount is in- jected into an animal before or together with the toxin it overcomes its poisonous action. This power Vol. I.— 54 is utilized in testing antitoxin. Guinea-pigs of about 250 gm. weight are subcutaneously injected with one hundred or with ten fatal dose "i toxin which have been previously mixed with an amount of antito in believed to be sufficient to protect from the to a. If the guinea-pig lives lour day.-, but di n after, the amount of antitoxin added to the toxin was just 1 or 0.1 unit, according as one hundred or ten fatal doses were employed. If the animal dies cm her, I. , than I unit was added. An antitoxin unit has thus been defined as "ten times the amount of antitoxic serum required to protect a guinea-pig weighing 250 gm. from death, when ten times tne fatal dose of toxin is mixed with the serum and the mixture in- jected subcutaneously into tile animal." The Uxe of Diphtheria Antitoxin in Treatment and Immunization. — tor the injection a hypodermic syringe is employed, holding 10 to 12 c.v., which mu i be previously thoroughly sterilized with alcohol and a livc-per-eent. solution of carbolic acid. The injection is made at some point on the anterior sur- face of the body, as the abdomen or thorax or outer surface of the thigh, where there is an abundance of subcutaneous cellular tissue. II. -lore injection the skin should be carefully washed with alcohol or some disinfecting solution. The serum is rapidly absorbed, and it is belter not to employ massage over the point of injection. For treatment of mild ca of diphtheria the dose is 1,500 antitoxin units, for moderate cases 2,000 to 4,000 units, and for severe eases 10,000 to 20,000 units. When no improve- ment follows in twelve hours the dose should be repeated. For immunization of children or adults who have been exposed to diphtheria the dose is from 300 to 500 units for an infant, 500 to 1,000 for an adult, and proportionally according to age, to be re- pealed if necessary at the end of two or three weeks. In all cases it is better to use a small quantity of a high-grade serum than a large quantity of a low-grade preparation, as there is in the former instance less danger of rashes and other deleterious effects. The only untoward results to be feared in any case in which proper aseptic precautions are taken in the in- jection, are occasional rashes with perhaps some slight rise of temperature, known as serum sickness. About 1 in 10,000 persons, within a few minutes after an injection of serum, develops alarming symptoms. About twenty deaths in all have been reported. Those suffering severe symptoms have usually been subject to asthma, while the fatal cases have the pathological changes known as status lymphaticus. In sus- picious cases of any severity, particularly in croup, it is better to administer the remedy at once, making a culture at the same time for bacteriological diagnosis, than to delay treatment until a positive diagnosis has been made by bacteriological examination. Concentrated Antitoxin. — Many attemps have been made to seperate the antitoxin from the serum, with a view to concentrate the dose and at the same time reduce the possible ill effects of the serum. A con- centrated antitoxic globulin solution is now made in the laboratoies of the Health Department of new York City, and by other manufacturers, which is being used in preference to the antitoxic serum and apparently with good results. The curative effects have proved to be identical with that of the whole serum and decidedly less severe rashes, etc., than formerly have been noted. The material used in the Health Department is blood plasma instead of blood serum. The globulins of the plasma are removed from the other non-anti- toxic or toxic constituents of albumin, cholesterin, lecithin, bile salts and acids, etc., by precipitation with ammonium sulphate. This precipitate contains the globulins of the blood which are antitoxic, those which are non-antitoxic, and nucleoproteins. The antitoxic globulins are extracted by treating with saturated 849 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES solution of sodium chloride, in which this compound is soluble. The antitoxic globulins are then isolated from the solution by precipitation with dilute acetic acid. The ammonium salts are washed out by repeated treatment with sodium chloride solution and filtered. Finally, the sodium chloride is removed by dialysis. After dialysis, the antitoxic globulins are dissolved in dilute saline solution, filtered to remove the traces of undissolved matter, passed through a Berkefeld clay filter to remove bacteria, and then put in sterile syringes. The concentration of antitoxin made possible by the elimination of the non-antitoxic substances is not only a convenience but is of distinct importance, a- it tends to encourage large doses as well as to re- duce to a minimum the serum or anaphylactic effects. The Bacillus op Tetanus (Bacillus tetani). — Nicolaier in 1884 produced tetanus in mice and rab- bits by subcutaneous inoculation of particles of gar- den earth, and showed that the disease was trans- missible by inoculation from these animals to others. Carl and Rattone soon after this demonstrated the infectious nature of tetanus as it occurs in man. Finally, in 1889, Kitasato obtained the bacillus of tetanus in pure culture and described its biological characters. Microscopical Appearances. — Slender rods with rounded ends, 0.3 to 0.8 ji in diameter by 2 to 4 p. in length, usually occurring singly, but often growing into long threads, especially in old cultures. Spore Formation. — Forms rounded spores thicker than the cells, occupying one extremity of the rods and giving them the appearance of minute drumsticks. (See Plate X., Fig. 3.) Motility. — Motile, although not actively so in hang- ing drop cultures with exclusion of air; numerous flagella are attached to the bodies of the bacilli. In the spore stage they are non-motile. Staining Reactions. — Stains with the ordinary aniline dyes, and is not decolorized by Gram's solution. The spores may be demonstrated by double staining with Ziehl's method. Biological Characters. — When freshly isolated from the animal body, this organism is strictly anaerobic; but by long cultivation at high temperatures it often becomes less sensitive to the presence of oxygen, this cultivation being facilitated by association with certain saprophytic bacteria. Carbone and Pessero have obtained from a case of rheumatic tetanus in which there was no sign of injury in the bronch al mucous membranes virulent tetanus bacilli, which grew more luxuriantly under aerobic than anaerobic conditions; in pure cultures, however, they proved to be non-virulent. The Bacillus tetani does not grow at temperatures below 14° C, though slowly from 20° to 24° C; best at 37° C, when it rapidly forms spores. It develops in the ordinary nutrient gelatin and agar media of a slightly alkaline reaction. The addition of 1.5 per cent, glucose to the media causes the development to be more rapid and abun- dant. According to von Hibler, the less pathogenic the organism the more luxuriantly it grows on arti- ficial culture media, and the more energetically it liquefies gelatin. In the animal body its growtli is comparatively scanty, and it is usually associated with other bacteria, pure cultures being difficult to obtain. Kitasato's method, which is not always successful, however, consists in inoculating an agar tube with the tetanus material (pus from wounds), keeping this for twenty-four hours or more in the incubator at 37° C, and, after the spores have formed, heating it for about an hour at S0° C. to destroy the associated bacteria. The spores of Bacillus tetani are able to survive this exposure, and anaerobic cultures are then made in the usual way, and the tetanus colonies isolated. 850 Growth on Gelatin. — On gelatin plates the colonies develop slowly, the middle portion being generally of a yellowish-brown color, with numerous threads radiating from the center; the gelatin is liquefied. In old cultures the entire mass is made up of fine threads, the colonies presenting an appearance not unlike that of the common mould. In gelatin stab cultures the growth exhibits the appearance of a cloudy, linear mass with outgrowths radiating into the medium from all sides. Liquefaction take< place slowly, generally with the production of gas having an unpleasant empyreumatic odor. Growth on Agar. — The colonies on agar are quite characteristic. To the naked eye they present the appearance of light, fleecy clouds; under a low-power microscope they resemble a tangled mass of threads. The extreme fineness of these threads enables the colonies of the tetanus bacillus to be distinguished from those of other anaerobic bacteria. In stab cultures on agar the growth resembles that of a miniat ure fir-tree. Alkaline bouillon is moderately clouded by the growth of the tetanus bacillus. It grows also in culture media, but itself produces no acid. Milk is not coagulated. Vitality. — The spores of tetanus are very resistant to outside influences, retaining their vitality for months or years in a desiccated condition and not being destroyed in two and a half months when present in putrefying material. They withstand exposure to 80° C, for an hour, but are killed by a temperature of 100° C. in five minutes. They resist the action of five per cent, carbolic-acid solution for ten hours, but succumb when acted upon for fifteen hours. The addition of 0.5 per cent, hydrochloric acid to the carbolic solution enables it to kill the spores in two hours. In a solution containing 1 to 1,000 bichloride of mercury, five per cent, carbolic acid and 0.5 per cent, hydrochloric acid, the spores are destroyed in ten minutes. Chemical Effects. — The tetanus bacillus produces gas in media containing sugar, but no acid. It forms sulphureted hydrogen abundantly and a little indol. It produces powerful toxins, which can be separated from the cultures by filtration. One one-hundredth of a milligram of an eight-day filtered bouillon culture is sufficient, as a rule, to kill a mouse. From this filtrate, however, the active toxin has been obtained in a much more concentrated form. The purified and dried tetanus toxin prepared by Brieger and Cohn was surely fatal to a 15-gm. mouse in a dose of 0.000005 gin. Reckoning according to the body weight of 75 kgm. or 150 pounds, it would require but 0.00023 gm., or 0.23 mgm., of this toxin to kill a man. Com- paring this with other known poisons, the appalling strength of the tetanus toxin can be readily appreci- ated. For instance, Calmette has found that dried cobra venom requires 0.25 mgm. to kill a rabbit of 4 kgm. weight, and it would thus require, at the same rate, 4.375 mgm. to kill a man of 150 pounds; the fatal dose of atropine for an adult is 130 mgm., of strych- nine from 30 to 100 mgm., and of anhydrous prussic acid 54 mgm. The true composition of the tetanus toxin is unknown; it has been shown, however, that it is neither an alkaloid nor an albuminous body. The quantity of toxin produced varies, even when derived from one and the same culture, according to its age, composition, reaction, etc. It is extremely sensitive to the action of light, most chemical agents, and heat. It retains its strength best in the dry state. Pathogenesis. — Man and almost all domestic animals are subject to tetanus. Among animals those most susceptible are horses, goats, guinea-pigs, and mice, less so rabbits and sheep; dogs, rats, pigeons and chickens are almost immune. It is worthy of note that an amount of tetanus toxin sufficient to kill a hen would suffice to kill 500 horses. A mere trace — only REFERENCE HANDBOOK ( >F THE MEDICAL SCIENCES Bacteria ,- much as remains clinging to a straight platinum die -of an old culture is often enough to cause I h leath of mice and guinea-pigs. ibcutaneous inoculation of virulent b Material mice and other susceptible animals .-how ■ymptom- of t\ pical tetanus in from one to three days. parts tirst to bo affected are, in about one- third nf he case- in man. and usually in animals, the muscles ying in the vicinity of the inoculation — for instance, hind foot of a mouse inoculated on that leg, then the tail, the other foot, the back and chest muscles an both sides, the fore leas, until finally there is a general tetanus of the entire body. In mild cases of infection, or when a dose too -mall to be fatal has been received, the tetanic spasm may be one-sided or remain confined to the muscles adjacent to the point of inoculation, and result in recovery. There may be no general increase of reflex excitability. In mat horses the local symptoms may be absent, but in- id tonic spa-in- of special muscles: in man, of the muscles of the jaw, and in horses of the muscli the jaw, neck, and tail. At the point of inoculation in test animals there may be on autopsy a hemor- rhagic -pot, but no chances here or in the interior lis other than this. A few bacilli may be detected lly with great difficulty, often none at all; appar- ently show ins; that the lesions produced are due. not to the multiplication of the bacilli in the living body, but to the absorption of the poison formed by them at the point of inoculation. It has been found that cultures freed from spores, and such as have been subjected to heat at 80° C, after sporulation and the toxins de- stroyed, can be injected into animals without pro- ducing tetanus. But if a culture of non-pathogenic organisms be injected simultaneously with the spores, or if there be an effusion of blood at the point of in- jection or a previous bruising of the tissues, the ani- mal will surely die of tetanus. It would seem, there- fore, from these experiments, that a mixed infection is necessary to the development of tetanus when the infection is produced by spores. This fact is of the greatest importance in natural tetanus, for here the infection may be considered as being probably always produced by the bacilli in their spore stage, and the conditions favoring a mixed infection are generally present. Tetanus bacilli and their spores have been found widely distributed in garden earth, hay dust, floors of dwellings and hospitals, on splinters of wood, old nails, in the air, etc. They have apparently been observed more frequently in certain localities than in others, as in some parts of Long Island and New Jersey, but they are probably equally distributed everywhere. This bacillus is the chief etiological factor in the production, not only of trismus and traumatic tetanus, but also of all the various forms of tetanus — puerperal tetanus, tetanus neonatorum, and idiopathic and rheumatic tetanus. Tetanus Antitoxin. — Behring and Kitasato were the fir-t to show the possibility of immunizing animals against tetanus. Here the question of immunity against infection does not consist in producing an increased power of resistance against the development of the infecting agent, but. similar to diphtheria, in bringing about an immunity to the effects of the tet- anus toxin. The methods originally proposed by B hring and by Roux for producing a serum for the treatment of the disease, consisted chiefly in weakening the tetanus toxin by means of chemical disinfectant- (iodine trichloride, Gram's solution, etc.), so that when inoculated into the te-t animals they produced com- paratively little reaction. At the present time pure unaltered toxin is injected either alone in small doses or along with antitoxin. After the first dose of toxin the animals acquire a certain tolerance which enables them to stand a dose of a less attenuated toxin or of a greater amount of unchanged toxin. Then by gradually increasing the doses or the strength of the toxin administered, the animal- are finally ah bear injections of large quantities of the toxin. These immunizing experiments in tetanus I borne practical fruit, for it was through them thai principle of serum therapeutics fu It was thus shown that animal- could be protected from tetanus infection by the previous or sum in' itoxin, pi o 1 anti- toxin was obtained froi oized animal; anil from tin- it was assui result could b I'm unfortunately, the conditions in thi disease are verj much less favorable, inasmucl treatment i- usually commenced, not shortly after the infection has taken place, but often only on the appear- of tetanic symptoms, when tic' poison ha- al- ready diffused itself through the body. The tetanus antitoxin is prepared in the same manner as the diphtheria antitoxin — by inoculatii g the tetanus toxin m increasing doses into horses. The toxin is produced in bouillon cultures grown f ally. After ten or fifteen days the culture fluid is filtered t hrough porcelain, an. I the germ-free Bltra used for the inoculations. The horses receive 0.5 c.c. as the initial dose of a toxin of which 1 c.c. kills 250,000 gm. of guinea-pig, and along with this a sufficient amount of antitoxin to neutralize it. In five day- this dose is doubled, and then every five to day-, a- rapidly as the horses .1 it, until they support 700-800 c.c. or more at a single < After some months of this treatment the blond of horse contains the antitoxin in sufficient amount for therapeutic use. When the temperatures of the horses are normal and they have recovered from the dose of toxin last given, they are bled into sterile flasks and the serum collected. Tetanus antitoxin is tested exactly as is diphtheria antitoxin, except that the standard unit is different. The test toxin used in the German method is one i f which 1 gm. destroys 150,000,000 gm. of mouse. This is dissolved in 33J c.c. of ten-per-cent. sodium chloride solution. Ten times the amount of antitoxic serum which neutralizes 1 c.c. of this dilution of the test toxin contains 1 unit of tetanus antitoxin. In the French method the amount of antitoxin which is required to protect a mouse from a dose of toxin sufficient to kill in four days is determined, and the strength of the antitoxin is stated by finding the amount of serum required to protect 1 gm. of animal. If 0.001 c.c. protected a 10-gm. mouse, the strength of that serum would be 1 to 10,000. Guinea-pigs are sometimes used instead of mice. The dose of tetanus antitoxin for immunization is 10 c.c. of a serum of a strength of 1 to l. in in. m n or about 1,500 units, unless the danger seem great, when the injection may be repeated after seven or eight days. For treatment it is well to begin with 50 c.c. or about 10.000 units, and then, according to the -everity of the case, give from 20 to 50 c.c. each day until the symptoms abate. The curative treatn in man has not been followed by very satisfactory results, owing to the fact already stated that the dis- ease is generally too far advanced before treatment is commenced. From statistics collected by Lambert and others, however, of cases of tetanus treated with antitoxin, the remedy would seem to have been of undoubted practical use — so much so. at least, that in all cases in which tetanus is suspected or in which dirt has been ground into serious contusions, in gunshot wounds, etc., preventive inoculations of the serum should be given. In certain parts of France where tetanus i- very prevalent among horses, Xocard distributed tetanus antitoxin to sixty-three veterinary surgeons, who treated with it. for the pre- vention of the disease, 2,727 of these animals. Only 851 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES one of this number became affected, and this horse was not inoculated until five days after being pricked in shoeing. Although the delay was too great to prevent the appearance of tetanus, yet the disease was of a very mild nature. During the same period 259 cases in animals that were not so treated were observed. These striking results would certainly seem to indicate that the remedy deserves a much more extensive consideration in the treatment of patients with immunizing doses of serum than has heretofore been given it — at least in neighborhoods where tetanus is not uncommon (fortunately it is a rare disease in man), and when the dirty condition of their wounds leads one to suspect the possibility of tetanus infection. Good results have followed this practice in many places. It is the custom at many dispensaries in New York City and elsewhere to immunize all Fourth of July wounds by injecting 1,000 units. None of these cases have developed tetanus. Even the eleven cases of human tetanus reported as occurring in Europe after single injections of antitoxin prove the value of immunizing injections, for the mortality was only twenty-seven per cent. The recently proposed method of injecting from 3 to 15 c.c. of tetanus anti- toxin into the lateral ventricles has not so far shown itself to be superior to the intravenous or subcutaneous methods, and is not in general to be recommended. No bad results have followed the injection of the antitoxin when the serum was sterile and the operation was performed aseptically. The Bacillus of Ttphoid Fever (Bacillus typhi abdominalis). — This organism was first observed by Eberth, and independently by Koch, in 1880, in the internal organs of typhoid cadavera. It was obtained in pure culture by Gaffky in 18S4; and has also been found during life in the blood, urine, and feces of typhoid patients. Its etiological relationship to typhoid fever has been somewhat difficult of demon- stration from the fact that, although pathogenic for many animals when artificially inoculated, it has not been easy to produce infection or give rise to lesions corresponding to those occurring in man. Still the results which have been obtained under certain conditions, together with the specific reactions of the blood serum of typhoid patients, and the constant presence of the bacillus in the spleen, blood, and excretions of the sick during life, have finally estab- lished, on a scientific basis, that this organism is the chief cause of typhoid fever. Microscopical Appearances. — As met with in the organs of man and animals the typhoid bacilli are short, plump rods with rounded ends. They vary in size, being from 1 to 3 n long and 0.5 to 0.8 ft broad, usually occurring singly, but sometimes growing into long threads, especially in certain culture media, as in potato. They are generally longer and some- what more slender than the bacillus coli under similar conditions. (See Plate VIII., Fig. 7.) Motility. — Actively motile, especially the short bacilli, each rod possessing from eight to fourteen flagella attached to the sides and extremities of the cells. The longer threads have a sinuous and more sluggish motion. (See Plate VIII., Fig. 8.) Spore Formation. — Does not form spores. In stained preparations, particularly when grown on potato, refractive granules may be seen at the ends of the rods, which stain more intensely, and in the body of the cells " vacuoles" which remain unstained. These so-called Gaffky 's spores, however, are not true spores, as the bacilli containing them show even less resisting power than the homogeneous bacilli found in other cultures, but are probably involution forms. Staining Reactions. — The typhoid bacilli stain with the ordinary aniline colors, but a little less readily than do most other organisms, though this is not constant. They are decolorized by Gram's solution. 852 Biological Characters. — The bacillus typhosus grows most luxuriantly in the presence of oxygen but oxygen is not essential to its development (facultative anaerobic); it grows fairly well also in an atmosphere of C0 2 . Its growth on the ordinary culture media is similar to that of the bacillus coli communis, but somewhat slower and not quite so abundant - in contradistinction to most other pathogenic micro- organisms, it grows well on slightly acid media. Be- low 10° C. it does not develop, its optimum tempera- ture being at 37° C; over 40° and below 30° C. it^ growth is retarded. Growth in Gelatin. — In gelatin plates the deep colonies are not characteristic; they are small, punctiform, and sharply circumscribed, of a yellowish- brown color and finely granular in structure. The superficial colonies, however, particularly when young, are quite characteristic; they form a bluish- white, transparent, iridescent coating on the medium, with irregular outline, denser in the center than at the periphery, and exhibiting under a low power a brownish color and wrinkled appearance. The gelatin is not liquefied. In gelatin stab cultures the growth is mostly confined to the surface; it is thin, thready, often slightly granular, extending along the track of the needle and gradually reaching out to the sides of the tube; white to yellowish brown in color, irridescent, and transparent. There is no liquefaction. Growth in Agar and Blood Serum. — Not distinctive. Growth in Bouillon. — This medium is uniformly clouded, but the clouding is not so dense as by the colon bacillus. After eighteen to twenty-four hours' growth a sediment is frequently developed, and a film forms on the surface, with a slightly acid reaction. Growth in Potato. — The growth in this medium is generally considered to be very characteristic, but it varies considerably. The typical growth is a slightly moist, almost invisible, but luxuriant layer, usually covering the surface of the potato, and when scraped with the needle is tough and tenacious. Sometimes, however, the development is restricted, not very luxuriant, and of the same color as the medium. Again, it may be quite heavy, of a yellowish-brown color with a greenish halo, and similar to that of the colon bacillus. These variations in growth are thought to be due to the reaction (alkalinity) of the potato. Milk is not coagulated, but some acid is produced by the typhoid bacillus. The Bacillus coli communis, on the contrary, causes coagulation of milk in twenty- four to forty-eight hours at 37° C. Vitality. — The typhoid bacilli withstand desiccation for months; according to Uffelmann in dried earth, clothes, etc., for two months or more. In dust, however, they do not seem to live so long. They resist cold remarkably well; freezing and thawing repeatedly under favorable conditions finally kills them. They are destroyed by heating to 60° C. in ten minutes and at higher temperatures still more rapidly. In feces the bacilli retain their vitality for weeks or months, depending upon the number of putrefactive organisms present. In oysters they have remained alive for a month. In water which has been sterilized they live for many days; in ordinary water they are destroyed, by the concurrence of other bacteria, in about fourteen days; in running water this destruction takes place more rapidly. It thus appears that, under favorable circumstances, protected from light and other deleterious influences, l he typhoid bacilli may retain their vitality outside of the body for a considerable length of time. But they may live also in the human body for a long time; Sahli has found them in the pleural exudate fifty days from the beginning of the disease, and Heintze observed them in a case of typhoid fever in periostitic pus ten months after convalescence. REFERENCE HANDBOOK OF THE MEDICAL S( ll\< Bacteria Chemical Effects. — The typhoid bacillus produces no pigment or odorous substances. It reduces litmus solutions; converts nitrates into nil rites, the Kilter being gradually decomposed; forms luetic acid from grape sugar, but does not produce gas from carbohydrates; produces 11. S abundantly, but does not produce indol. The cultures are rich in toxins !i, when freed from germs by filtration, are active disease producers. Pathogenesis. — Although the typhoid bacillus is pathogenic for mice, guinea-pigs, rabbits, goats, etc., which when inoculated with virulent cultures die, showing symptoms of spasm, falling temperature, and diarrhea, no experiments so far have produced in animals the typical lesions of typhoid fever in man. iin experiments have indicated thai the presence oi other bacteria in the body, and of exposure to the action of poisonous gases in lowering the natural resistance of the individual, may render him more ceptible to typhoid infection. But whatever conclusions may be drawn from these results with regard to the typhoid process in animals, in the human subject typhoid fever is now generally recog- ied as a true infection, caused by the invasion and growth of typhoid bacilli in the body. This disease belongs to the class of infections known as metastatic — that is to say, diseases in which the specific infective organisms do not abound in the circulation, as in septicemia, nor remain localized in one situation, but are distributed through the body in groups, the characteristic lesions of typhoid fever being in the lymphatic structures of the intestines, viz., the solitary follicles and patches of Peyer, the mesenteric glands, and the spleen; the liver and kidneys are less commonly affected. Outside of the body the typhoid bacilli have been found so far only in comparatively few instances in water and soil, which have become contaminated with typhoid dejections; also in milk. They have been found in healthy persons who have been in close association with typhoid patients, and those con- valescent from typhoid fever. (See section on Typhoid Carriers, below.) In typhoid patients they have fre- quently been detected in the spleen and other organs (kidneys, liver, gall duct, etc.), the blood, urine, and feces. They are most easily isolated from the spleen and lymphatic glands; they are often difficult to isolate from the excretions. The typhoid bacillus may give rise to the most varied complications along with the clinical symptoms of typical typhoid fever; it has been demonstrated to be the cause of suppurative in- flammations of the spinal cord, of the brain and its membranes, of the lungs and kidneys, and of different suppurative processes, erysipelas, abscess, etc., in typhoid patients. The pyogenic functions of the typhoid bacillus are indeed no longer disputed. But at the same time in many cases of mixed infection in typhoid fever, the other pus cocci (streptococcus, staphylococcus, pneumococcus, etc.) are no doubt concerned in the production of the complications of the disease. With regard to the mode of infection by the typhoid bacillus, there is no doubt that it is principally by way of the mouth and stomach to the intestines through drinking water, etc. In a case reported by Mayer in which death occurred on the second day of the disease, there were found on autopsy lesions of the lungs, spleen, kidneys, and intestines and great enlarge- ments of the solitary follicles and patches of Peyer, but nowhere a trace of necrosis or loss of substance nor enlargements of the mesenteric glands. Microsco- pically an extraordinary deposit of characteristic typhoid bacilli was observed in the submucosa and interstitial spaces of the muscular tissue. In other cases, however, no intestinal lesions have been present, only a localization of bacilli and changes in the mesenteric glands and spleen revealing the nature of the infect ion. I [ere ftb orpl probabl; place more rapidly than usual, the bacilli not' multi- plj ing to :m\ i iiivs. Hut not only do tin. i : i which ha i e been examined bacterio- logically and pathologically, but also the epidemiologi- cal hi ioiv of typhoid fever, prove beyond que that the chief i le of invasion of tin pecific bac- illus is by way of the mouth. The infective matt rial discharged in the feces and mine of typhoid 1 patient- in the latter of whii icilli often persist for weeks or month coi I u unate the water supply, articles of food, hand- of nurses and attendants, etc., and thus spreads infection from place to place. (In this account the disinfection of tin- dejections of typhoid patients and convalescent cannot I"' too carefully looked after. Typhoid Carriers. — Examinations of convali cent typhoid cases show that about one to five per cent, con- tinue to pass typhoid bacilli for years, perhaps for life. The focus of infection i.- believed to !»• in either the gall-bladder, chronic ulcers of the intestines, or the normal intestinal tract. The majority are women. A remarkable case has been noted in New York of a cook who carried typhoid infection to other persons with whom she was associated for six years ll'.ltll to 1907). Another remarkable instance is one in which some hundreds of cases of typhoid fever were t raced to a milk supply produced at a farm looked after by a typhoid carrier who had had typhoid fever forty- i years before. .Medicinal treatment has so far yielded only slight results (See Bacteria Carriers.) Immunization. — Specific immunization against ex- perimental typhoid infection has been produced in animals by the usual method of injecting at first small quantities of the living or dead typhoid culture and gradually increasing the dose. The blood serum of animals thus immunized has been found to acquire pro- tective and curative bactericidal and possibly feeble antitoxic properties against the typhoid bacillus. These characters have also been observed in the blood serum of persons who have recovered from typhoid fever; and recently the attempt has been made to employ the typhoid serum of immunized animals or dead cultures for the cure and prevention of typhoid fever in man, but no marked results have been obtained. Vaccination against Typhoid. — The use of killed typhoid bacilli as vaccine has been advocated by Wright. Two injections are usually given. The first of 500 millions and the second, ten days later, of 750 millions. If it is impossible to count the number, 0.1 c.c. and 0.3 c.c. of a bouillon culture can be given. The bacilli are heated to 60° C. for thirty minutes or killed by 1/2 per cent, lysol or carbolic acid. For a day or two the injection produces a slight fever, a local pain, followed by the development of bacteri- cidal substances in the blood, apparently sufficient in amount to give some immunity lasting for a year or more. A second injection adds to the degree of immunity. In 49,600 individuals under observation in India and Africa, S,600 were thus treated. The disease appeared in them to the extent of 2.75 per cent, with a case mortality of 12 per cent. In 41,000 inoculated there was a case percentage of 5.75 per cent, anc' a case mortality of 26 per cent. The use of protective vaccine in the shape of dead cultures, would therefore, seem to be advisable where dancer of typhoid infection exists. This practice of vacci- nation against typhoid has recently been introduced into the 1". S. army. Specific Reactions. — The following specific reactions have oeen utilized for the differential diagnosis of the fcyi l, aid bacillus from other similar organisms, and as in aid to the clinical diagnosis of obscure cases o typhoid fever: 1. The typhoid bacillus does not produce indol. 2. It does not produce fermentation or gas from media containing grape sugar, milk, or cane sugar. 853 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES 3. On lactose litmus agar it grows usually as pale blue colonies, but occasionally causes slight redness of the surrounding medium. 4. Widal's Serum Reaction. — This reaction is based upon the fact, first observed by Pfeiffer, Gruber, and Durham, but since practically applied on a more ex- tended scale by Widal, that living and actively motile typhoid bacilli if placed in the diluted blood or serum of a patient suffering from typhoid fever, within a very short time lose their motility and be- come aggregated into clumps. Either dried blood or serum may be used for the demonstration of the reaction. The blood is obtained by pricking with a needle the skin (previously disinfected) covering the tip of the finger or ear, and allowing two drops to fall on a glass slide, one near either end, when they dry. Fluid blood serum may be obtained in two ways: First, the tip of the finger or ear is pricked and the blood as it issues is allowed to fill by gravity a capil- lary tube havig a central bulb, the ends of the tube being then sealed by heat and the serum allowed to separate from the clot. Second, a small piece of cantharides plaster is applied to the skin at some spot on the chest or abdomen, and from the blister thus formed in six to eighteen hours, the serum is collected in a capillary tube, the ends of which are then sealed. The latter method is the best, for the serum obtained is clear, free from blood cells and fibrin, which some- what obscure the field on examination in the hanging drop, and is admirably suited to the test. Dried blood, however, obtained as above described answers all practical purposes of diagnosis. The method of performing the serum test is as follows: A dilution of the blood or serum is first made in the proportion of one to ten. In the case of dried blood, it is dissolved in a little water and then mixed with the typhoid culture (eighteen to twenty- four hours old), the degree of dilution being guessed by the color. By previously making test solutions of dried blood in water of known proportions and noting the color the dilution may be approximately gauged. If serum is used, which is preferable not only because there is less fibrinous deposit but also be- cause it is possible to make the dilution more accur- ately, one part of serum is added to nine parts of the broth culture. This should contain living and actively motile isolated bacilli. If there is no reaction when the mixture is observed in the hanging drop — that is to say, if within five minutes no marked change is noted" in the motility of the bacilli and no considerable clumping occurs — the result may be regarded as negative, and no further test of the specimen is neces- sary. If complete clumping and immobilization of the bacilli occur within five minutes, this is a marked immediate typhoid reaction, and though this test is ordinarily sufficient for a positive diagnosis, the reaction may be confirmed with higher dilutions up to one to twenty, or more, if desired. If, however, upon examination of the mixture there is no marked reaction, but the bacilli only show in the first few minutes an inhibition in their motility and a ten- dency to clump, not complete within five minutes, it becomes necessary to test this with dilutions up to one to twenty, in order to measure the strength of the reaction. If in the one-to-twenty dilution a com- plete, distinct reaction takes place within thirty min- utes, the result may also be considered positive, that is that the blood or serum has come from a case of typhoid infection, while if a less marked reaction occurs it should be regarded as only probably typhoid, and another specimen should be requested. The time allowed by many observers for the develop- ment of the reaction with the higher dilutions is from one to two hours, but thirty minutes, in our opinion, is a safer and sufficient time limit. Positive results obtained in this way may be accepted as conclusive evidence of the recent or previous existence of typhoid infection in the patient. A former attack of typhoid fever within a period of several months or one or more years exceptionally vitiates the value of the reaction. On the other hand, the absence of reaction in any one examination does not exclude typhoid- so that, if the case remains clinically doubtful, re^ peated examinations should be made. If too 'con- centrated a solution of dried blood from a healthy person is employed a pseudoreaction is often obtained which may be mistaken for a true reaction. Dis- solved blood always shows a varying amount of detritus, partly in "the form of fibrinous clumps, and the bacilli, inhibited by substances in the blood, may become entangled in these substances simulating a reaction. This is an important point to bear in mind. In pseudoreaction, however, it may be noticed that many free bacilli are apt to be gathered at the margins of the hanging drop. The Widal reaction, though not infallible, when performed with due regard to the avoidance of every possible source of error, is as reliable as any other bacteriological tesl at present in use, and is of inestimable value as an aid to the clinical diagnosis of irregular or mild cases of typhoid infection. It is simple and easy of per- formance by any one versed in bacteriological tech- nique. The serum reaction is never present in other diseases or in healthy persons, if correctly made and in the proper dilution, as is so often the case with Ehrlich's diazo reaction. It is better adapted for general employment than are any of the cultural methods now in use for isolating the bacillus from the feces or urine. It is certainly safer than spleen puncture, and it is not so difficult as, though far more reliable than, the leucocyte count. The reaction does not appear, as a rule, during the first few days of the disease, but it is usually manifest before the rose- colored eruption appears, though occasionally it is very late in appearance (that is, not till the fourth or fifth week and sometimes only during a relapse), and in rare cases may be entirely absent. Although a negative result, therefore, has but little significance, a positive reaction when present — previous typhoid being excluded — is almost as strong evidence of the existence of the specific infection as the actual demonstration of the typhoid bacilli. Ice Pollution in the Production of Typhoid Ferer.— Although there have been a few cases of typhoid fever which have been directly traced to ice infection, the fact that freezing kills a large percentage of typhoid bacilli in water makes the danger of the pro- duction of the disease from ice pollution very slight, except under extraordinary conditions. It is always much less than the use of the water itself. Every week that the ice is stored the danger becomes less, so that at the end of four weeks it has become as much purified from typhoid bacilli as if subjected to sand filtration. At the end of four months the danger is almost negligible and at the end of six months quite so. The possibility, however, of even slight danger of infection from freshly cut ice sugpi-i- tlie advisability of condemning any portion of rivers, etc., greatly contaminated by sewage, for harvesting ice for domestic purposes — such ice to be used only where there is absolutely no contact with food. The Colon Bacillus (Bacillus coli communis).— This type of organism was first described by Emmer- ich (1885), who obtained it from the blood,_ organs, and intestinal discharges of cholera patients at Naples under the name Bacillus neapolitanus. It has since been found to be a normal inhabitant of the intestinal canal of man and many animals. A number of similar bacterial species are now often spoken of as the colon group of organisms. The colon group has interest not only because it excites disease at times in man and animals, but also because it is an index of fecal pollution from man or animals. 854 ukfi:i:eni lobar pneumonia; in one hundred and twenty-nine cases examined by Weichselbaum the pneumobacillus was found in nine. According to Netter and Weichselbaum the cases due primarily to this organism are distinguished by their peculiarly malignant type and by the viscidity of the exudate produced. It is also probably concerned, primarily or secondarily, under certain circum- stances, in the production of pleurisy, abscess of the lungs, pericarditis, endocarditis, otitis media, and meningitis, in all of which diseases it has been found at times. It has been met with in all the organs of the body and also in the blood. The Pus-producing Organisms. — Many bacteria are capable of producing, under certain conditions, inflammatory and suppurative processes, abscess, cellulitis, septicemia, etc. The microorganisms most commonly found associated with suppuration are staphylococci, streptococci, pneumoeocci, and tetracocci. The following species are also occasion- ally met with: the colon bacillus and allied members of that group, the typhoid bacillus, the influenza bacillus, and the bacillus pyocyaneus. In so-called "cold abscesses" the tubercle bacillus is usually the only organism present. Besides these bacteria, other species may sometimes cause circumscribed suppurative processes. Staphylococcus Pyogenes Aureus. — This is one of the commonest pathogenic bacteria, being present almost everywhere. It is the most frequent cause of acute circumscribed suppurative inflammations. Though first observed by r Pasteur (1880) in pus and by Ogston (1881) in acute abscesses, it was not obtained by him in pure culture but was isolated and accurately described by Rosenbach in 1884. Microscopical Appearances. — Small, spherical cells, having a diameter of about 0.8/1, occurring singly or in pairs, but usually' arranged in irregular masses simulating clusters of grapes; hence the name, from crracpvX-n, "grape." (See Plate IX., Fig. 3.) Motility. — N on-motile. Staining Reactions. — Stains easily in aqueous solu- tions of the basic aniline dyes; is not decolorized by Gram. Biological Characters. — Aerobic and facultative anaerobic, but produces pigment only in the presence of oxygen. It grows readily at a temperature of from 1N° to 20° O, but best at 25° to 35° C., on all the ordinary culture media. Growth on Gelatin. — Grown on gelatin plates at room temperature, it develops within forty-eight hours punctiform colonies, which, when examined under a low-power lens, appear as circular discs of a pale or yellowish brown color, somewhat darker at the center and surrounded by -i transparent zone with well- defined border. Immediately around the colonies, which grow rapidly and are slightly granular in structure, there is a deepening of the surface of the gelatin, due to its liquefaction. Later, the lique- faction becomes general, the colonies running to- 857 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES gether. In gelatin stab cultures a white confluent deposit first develops along the line of puncture, followed by liquefying of the medium in the form of a stocking. At the end of two days the yellow pig- ment begins to form, and this increases in intensity until finally (after a week) complete liquefaction takes place and the "golden staphylococci" fall as an orange-colored deposit to the bottom of the tube. Under unfavorable conditions the staphylococcus aureus gradually loses its property of liquefying gelatin and producing pigment. Growth in Agar. — In streak and stab cultures on nutrient agar a whitish growth is at first produced, and this after a few days also becomes golden yellow on the surface. Colonies found at the bottom of a stab culture or under a layer of oil remain white; showing the inability of this organism to produce pigment in the absence of oxygen. Bouillon is densely clouded by the luxuriant growth. Milk is coagulated in from one to eight days with the production of acid. Chemical Effects. — The production of an orange- yellow pigment, but only in the presence of oxygen; agar cultures smell like glue or spoiled paste; gas and acid production from carbohydrates; the production of H,S abundantly and a little indol; the decom- position of urea by certain species — these are the chemical effects of the staphylococcus. Vitality. — Several cases of osteomyelitis have been reported in which staphylococci have been found alive in the body in the centers of infection after many years, during this time having been encapsulated apparently. In cultures they retain their vitality for a year or more. The staphylococcus is distinguished from most other pathogenic bacteria by its greater power of resistance to all outside influences, desicca- tion, heat, chemical agents, etc. It does not, how- ever, form spores, as far as we know. In dried pus, according to Hiigler, it stands desiccation for from fifty-six to one hundred days. But it is rapidly killed by moist heat at 70° C. It retains its vitality in ice sixty-six days (Prudden). Disinfectants act on it slowly. Meade Bolton found that a one-per- cent, carbolic acid solution destroyed it in two hours; mercuric chloride 1 to 1,000 killed it in five to ten minutes. But there is a considerable difference in the resisting power of the micrococci. Pathogenesis. — The pathogenic effect of the Staph- ylococcus pyogenes aureus on test animals varies much according to the mode of application and the viru- lence of the culture employed. Experiments have shown that this organism as found in suppurative processes in the human subject is not as infectious for animals as it is for man. The order of suscep- tibility seems to be as follows: man, horses, dogs, cattle, goats, sheep, rabbits, guinea-pigs, mice. In man a simple rubbing of the unbroken skin with pus from an acute abscess is usually sufficient to produce purulent inflammation. Cutaneous inoculation of animals is negative, but subcutaneous injection causes a local abscess in rabbits, guinea-pigs, and mice, and intravenous injection in rabbits sometimes produces pyemia and, after injury to the cardiac valves, ulcerative endocarditis. The filtrates from bouillon cultures contain highly virulent toxic substances. Injection of these into the peritoneal cavity of dogs causes serosanguineous peritonitis, and ecchymoses in the serous and mucous membranes of the intestines, finally resulting in death with bloody diarrhea. Immunity against staphylococcus infection may be produced by the injection of gradually increasing doses of the pure culture either living or previously sterilized by boiling. The blood serum of animals which have been thus immunized possesses slight protective and curative effects in other animals, but no practical use of this scrum has been attempted in man. 858 Staphylococcus aureus occurs outside the body in milk, water, soil, air, etc. Ten per cent, of the microorganisms present in the air of surgical clinics consist of staphylococci (Ullmann). It is found on the healthy skin, in the mouth, vagina, cervix uteri and milk of nursing mothers. It is trie chief cause of all acute inflammatory suppuration, in many cases the sole cause. It is commonly found, however, in association with streptococci, pneumococci, colon bacilli, typhoid bacilli, etc. The following affections particularly are frequently caused by the Staphylo- coccus aureus and other species: acne, sycosis. impetigo, pemphigus, conjunctivitis, furuncle, abscess, periostitis, osteomyelitis, parotitis, tonsillitis, manmii- l is, ulcerative endocarditis, pyelonephritis, etc. It is the principal etiological factor in the production of pyemia in the various pathological forms of that condition. Not all persons, however, are equally susceptible to infection by the staphylococcus; those who are in a cachectic condition or suffering from constitutional diseases, like diabetes, are especially liable to infection. In healthy individuals certain parts of the body, as the back of the neck and seat, seem to be more subject than others to attack by furuncles, carbuncles, and the like. In persons in whom sores are readily produced in consequence of disturbances of nutrition, the micrococci find a suitable resting place at the points of least resistance, as in the bones of weakly children, in fractures, and injuries in general. Staphylococcus pyogenes albus is morpho- logically identical with S. pyogenes aureus, and is probably a variety of the same organism winch has lost its power of producing pigment. On the average it seems to be somewhat less pathogenic. Staphylococcus pyogenes citreus is also proba- bly identical with the above-mentioned species, except that it forms by its growth a lemon-yellow pigment. It is found in about ten per cent, of cases in the pus of acute abscesses, usually in association with other pyogenic cocci. Staphylococcus epidermidis albus is another variety no doubt of S. pyogenes albus, but found on the surface of the body and often in parts of the epidermis deeper than can be reached by any known means of cutaneous disinfection except by heat. According to Welch it is far less virulent than S. pyogenes aureus. It is frequently present in aseptic wounds, but does not seem to interfere with their healing, although sometimes it may cause suppuration along the drainage tube, and is the common source of "stitch abscess." Micrococcus Tetragenus (Tetracoccus).- — This micrococcus was discovered by Koch in 1884 in a phthisical lung cavity. Gaffky made a further study of it and described its pathological properties for various test animals. Biondi found it in human saliva; here, however, it is sometimes simply an evidence of mouth contamination, not of lung infection. In pulmonary tuberculosis it is commonly associated with other pathogenic bacteria, which, though playing no part in the etiology of the primary affection, contribute no doubt to the progresshe destruction of the lung tissue. Its pyogenic character is shown by its not infrequent presence in the pus of acute abscesses, empyema, etc. Microscopical Appearances. — When obtained from the animal body it occurs mostly in groups of four surrounded by a capsule. In cultures the cocci are seen in various stages of division as large round, undivided cells, in pairs of oval elements, and in groups of three or four. When the division is com- plete they remind one of sarcina in appearance, except that they divide in four instead of in three REFERENCE HWDBoiiK OF Til It MEDICAL S( [ENCE8 Bacteria directions and arc not built up like, cotton bale . (See Plate 1\ , Fig. 4.) Motility. — Non-motile. Stain iiui Reactions. — Stains readily with the ordi- nary aniline dyes; is not decolorized by Gram. Biological Characters. — Grows both in the presence and in the absence of oxygen, bul best with oxygen, in the usual culture media. It may be cultivated al room temperature (20° ('.); the optimum being I" tween 35° and 38° ('. The growth is slow under all conditions. Growth in Gelatin. — On gelatin plans small, white to grayish-yellow, shiny, prominent, round, or lemon- sbaped colonies develop. In gelatin stab cultures it ts equally as well on the surface as along the . of the needle; forming on the surface a thick, white, shiny iii:bs and tilling out the fissures along the line of puncture. The gelatin is not liquefied. On agar and blood serum the growth on the sur- is moist and glistening. The colonies appear as small, transparent, round points of a grayish-yellow color and slightly elevated. Pathogenesis. — Subcutaneous injections of a cul- ture of this micrococcus in minute quantity are usually fatal to white mice in from three to six days. The organisms are found chiefly in the spleen, lung-, liver, and kidneys, few in the blood. Gray mici generally immune. Rabbits and dogs are also little ■ptible. In guinea-pigs only a local reaction or abscess sometimes follows inoculation, and again they die from septicemia; intraperitoneal injections produce purulent peritonitis, groups of micrococci being found in the exudate. Streptococcus Pyogenes (Streptococcus erysipe- loid*). — This microorganism was first observed by Koch in stained sections of tissues attacked by septic processes, and by Ogston in the pus of acute abscesses (1882). It was obtained in pure cultures by Fehleisen (1SN3) from a case of erysipelas, and its pathological properties proved. Rosenbach (1884) and Krause and Passet ( 1885) isolated it from pus and gave it the name of streptococcus pyogenes. It has since been shown to be the chief cause of many suppurative inflammations. Formerly the streptococci of ery- sipelas, acute abscess, septicemia, puerperal fever, etc.. were thought to belong to different species, because they possessed certain differences in their pathological effects and morphological peculiarities, according to the source from which they were derived. But now it is recognized that these slight differences are not sufficient to constitute separate species, but only varieties of the same species. At the same time, however, there would appear to be some strep- tococci, which, in so far as their specific reaction in the presence of a protective serum is concerned, are as distinct from the streptococcus pyogenes as is the pneumococcus. This question is of practical impor- tance, for upon its solution depends our ability to select a suitable protective serum in different cases of streptococcus infection. Microscopical Appearances. — Spherical micrococci from 0.4 to 1 p. in diameter, usually larger than the staphylococci, characteristically arranged in chains of eight, ten, twenty, or more elements, but also associated in pairs and sometimes in irregular masses. (See Plate IX., Fig. 2.) Motility. — Non-motile. Staining Reactions. — Stains easily with all the basic aniline dyes and by Gram's method. Biological Characters. — Facultative anaerobic, grow- ing in both absence and presence of oxygen, and on the various liquid and solid culture media. The growth is slow, developing best at from 30° to 37° C, but also at room temperature (18° to 20° C). There is no growth over 47° C. Growth on Gelatin.— In gelatin plates small, white to yellowish or brownish granular round colonies de- velop, which do not liquefy the gelatin; though occa tonally, with unusual variel ies, a amount of liquefaction has been observed. Under a high power, chains of streptococci may l>e seen projecting from the sides of the discs. In gelatin slab cultures the growth i not confluent, bul individual colonies are arranged beside one another along lie- Iii,. punei up . Growth an Agar. — (in agar plates the colo visible after t - hirty hours' growth, and when magnified sufficiently show beautiful chain cocci "i!e N iii i he form of twisti d loops. 1 lie colonii circular in shape when thinly scattered over the plates, but irregular when crowded together. Gro . — The growth iii thi- medium is variable in different varieties; in slightly alkaline bouillon at -u " C. reaching their full development within thirty-six to forty-eighl hours. Streptococci which grow in long chains usually give an abundant floerulent deposit and leave the liquid clear; I he deposit may, however, he granular, in Larger Hake- or in tough masses; sometimes the broth i- clouded. Those growing in short chains, as a rule, cause dil clouding of the bouillon, with a granular deposit at the bottom of the tube. The development in a mixture of ascitic fluid and bouillon, which is t In' bi ' medium for the growth of the streptococcus, is more abundant than in plain bouillon. Growth in Solidified Blood Serum. — This is also an excellent medium for the cultivation of the strepto- coccus. Tiny grayish colonies appear after twelve to eighteen hours. Milk is usually coagulated with the production of acid, but not always. The growth on potato is scanty. Development of Hemolytic Substances. — Most strep- tococci produce these. This is especially true of those from human septic infections. As pneumococci and some types of streptococci produce them in a much less degree, blood agar plates are a very useful means for a probable identification. If 1 c.c. of fresh or defibrinated blood is added to 6 c.c. of melted agar at 40° to 45° C, well shaken, inoculated with characteristic streptococci and poured in a Petri dish there will appear in twelve to twenty-four hours tiny colonies surrounded by clear zones of about J to J inch in diameter. Pneumococci and many other varie- ties of streptococci, which occur together with char- acteristic forms in the throat, lungs, etc., on the other hand produce only narrow zones of a green pigment. Vitality. — Cultures of the streptococcus die much sooner than those of the staphylococcus, very few living over a month and the majority dying within a few days; they live longest in serum bouillon or a mixture of ascitic fluid and bouillon, and may be kept thus for a considerable time in small sealed glass tubes in the ice chest. When dried in blood or pus, the streptococci retain their vitality for several months at room temperature, and still longer in the refrigerator. The thermal death point, according to Sternberg, is between 52° and 54° C, the time of exposure being ten minutes. Chemical Effects. — As products of their growth the streptococci form but little pigment, no indol, a little H 2 S, and as a rule no acids or gases from carbohy- drates. From albuminous culture media they pro- duce toxins which are precipitated by alcohol but are soluble in water. To obtain these toxins the cultures are killed by r chloroform or filtered through porce- lain. Introduced into animals in considerable quan- tities they cause suppuration and fever and even death; they seem to belong to the class of so-called toxalbumins. Pathogenesis. — The majority of test animals are not very susceptible to infection by the streptococcus, and hence it is difficult to obtain any definite pat holog- ical changes in theirtissues by inoculations of cultures. 859 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES White mice and rabbits are the most susceptible, and these animals are, therefore, usually employed for ex- perimentation. The virulence of streptococci, how- ever, varies greatly for animals and is different from their virulence for the human subject. The most viru- lent cultures, when injected in small quantity into the circulation or the subcutaneous tissues of a mouse or rabbit, produce death by septicemia. Less virulent varieties require the injection of large quantities to produce a similar result, while some produce only abscess or erysipelas when injected subcutaneously, and others have no effect at all when introduced directly into the circulation. Many of the strepto- cocci obtained from cases of cellulitis, abscess, empyema, and even septicemia belong to this group. A number of varieties of streptococci have thus been discovered, differing in virulence and in their growth in culture media; but all attempts to separate them into classes, until recently through the use of spe- cific serum, have failed, because the differences ob- served, though often marked, are not constant. Knorr has enunciated the following important facts with regard to the virulence of streptococci: All varieties when cultivated for any length of time on artificial media gradually lose their virulence. By con- tinuous passage through certain susceptible animals, as mice, a streptococcus is obtained which is very pathogenic for those animals, but at the same time has lost its virulence for others, as rabbits. The more virulent any variety of streptococcus is for an animal, the more certainly it kills without suppura- tion, which is produced only by less virulent forms. There seems also to be a strong tendency for a strepto- coccus to produce the same kind of inflammation, when inoculated, as the one from which it was derived; for example, streptococci from erysipelas tend to pro- duce erysipelas, from septicemia to produce septice- mia, etc. Streptococci, however, obtained from different sources (abscesses, puerperal fever, sepsis, erysipelas, etc.) are sometimes capable of producing erysipelas when inoculated into the ear of a rabbit, provided they possess sufficient virulence. By con- tinued passage of fatal doses through susceptible animals Marmorek has obtained cultures of strepto- cocci of such virulence that 0.0001 c.c. subcutaneously injected into mice almost invariably killed them, while 0.000001 c.c. sometimes produced death — i.e. in amounts which contained but a verv few organisms. According to this investigator, the virulence may be retained by cultivation in mixtures consisting of two parts of serum and one part of bouillon, or one part of ascitic or pleuritic fluid and two parts of bouillon, such cultures being kept for two months or more without transplantation to fresh media. Streptococci have been found outside the body in the soil, in water, and in the air of surgical clinics, etc. In healthy persons they have been observed in the mouth, nasal cavities, vagina, and infrequently in the cervix uteri, sometimes in virulent forms. The Streptococcus pyogenes may give rise in man to a number of inflammatory and suppurative processes. It is frequently the primary cause of infection in erysipelas, acute abscesses, cellulitis, lymphangitis, tonsillitis, bronchitis, pneumonia, sepsis, puerperal fever, impetigo contagiosa; less commonly in pleuritis, pericarditis, meningitis, periostitis, osteomyelitis, otitis media, mastoiditis, empyema, etc. Associated with other bacteria in diseases of which they are the specific cause, streptococci have also been found contributing to secondary or mixed infection in pulmonary tuberculosis, bronchopneumonia, scarlet fever, and septic diphtheria, playing an important part in these affections in the production of septicemia and fever. So uniformly present are streptococci in the pseudomembranous inflammations of scarlatina that some authorities -have claimed that a certain variety of streptococci (Streptococcus conglomcratus of Kurth 8G0 and Klein) is the specific cause of this disease. The same is true for smallpox. Their abundance in scar- let fever and smallpox is most probably due to their in- crease in the injured mucous membrane and entrance into the circulation when the protective properties of the blood have been lowered. 5. pyogenes is further the probable cause of a number of cases of nephritis arthritis, and myelitis, being frequently found in the blood and urine, with or without sjmiptoms of general intoxication. In animals such as horses, asses, cows, sheep, goats and dogs, the streptococcus also produces diseases similar to those observed in man. These organisms have not infrequently been found in the vaccine lymph of stations where this is prepared, though generally they are the non-virulent varieties. Almost all of the diseases above mentioned have been produced experimentally in animals, the result depending upon the susceptibility of the animals employed, the virulence of the streptococci and the amount of infective material injected. The causal relation of this organism to disease has also been demonstrated in man. Fehleisen has inoculated cultures obtained from the skin of patients suffering from erysipelas into persons with inoperable malig- nant growths — lupus, carcinoma, and sarcoma — and has produced a typical erysipelatous inflammation in from fifteen to sixty hours. Persons who had recently recovered from an attack of erysipelas proved to be immune. In such persons also it was observed that malignant tumors apparently improved or entirely disappeared after inoculation. This fact has been made use of in the treatment of cancers by the artificial production of erysipelas through inoculation of pure cultures or of their toxic products, and in some cases of spindlecelled sarcoma, according to Coley, with considerable success; in carcinomata the results have been very slight. Susceptibility and Immunity. — As with the staphylo- coccus, the streptococcus is more liable to invade the tissues and produce inflammation and suppuration when the standard of health is reduced from any cause, and especially when by absorption or retention toxic products are present in excess in the body. Thus local streptococcus infections are more likely to occur as complications or sequel® in various specific diseases, in chronic alcoholism, in constitutional affections in those exposed to septic emanations from sewers, etc., and in cases in which there is absorption of toxic products formed in the alimentary canal as the result of the ingestion of improper food, of con- stipation, etc. Just as in persons who have recovered from an attack of erysipelas there has been observed a slight immunity to further infection, so it has been found that animals, after recovering from artificial inocu- lation of the toxic products of the streptococcus, acquire a moderate immunity, which may be increased by the administration of gradually increasing doses of the culture. In this way Knorr has immunized rabbits against an intensely virulent streptococcus by injections of slightly virulent cultures; Pasquale has partially immunized these animals against sep- ticemia; and Marmorek has protected sheep, asses, and horses against very large doses of a streptococcus which though but slightly virulent for them was intensely so for rabbits. In none of the streptococcus infections in man, however, are there apparently produced lasting im- munizing substances in the blood after a single attack. In cases of erysipelas, cellulitis, and abscess, recovery after periods varying from a few days to several months would seem to indicate the presence of slight or transitory protective substances; but the severe forms of infection, such as septicemia following operations and puerperal fever, show little tendency to recovery when once well established. REFERENCE HANDBOOK OF THE MFDICAL SCIENCES Bacteria Marmorek was the first to attempt to produce a curative antistreptococcus serum obtained from immunized animals (asses and horses) for the treat- ment of streptococcus infections. The re ults re- ported from the use of this serum since his first c - munication in 1895 have been very variable. The protective power of antistreptococcus serum is un- doubtedly specific, but it soon loses this power and often is practically useless six weeks after its prepare tion. Definite protection, however, from the serum has been obtained by many reliable observers since Mannorck's first reports. It has been shown that the same serum does not always confer immunity to other varieties of streptococci than the one which was originally employed in the immunizing inocula- tion. But the results of numerous investigators would seem to indicate that the majority, though not all. of the streptococci met within cellulitis, erysip- elas, and abscess will be influenced by the same serum, while those obtained from cases of pneumonia and endocarditis and other exceptional infections are apt to have individual characteristics. In order, there- fore, that the scrum may have specific antibodies for the variety of streptococcus causing each separate infection it is now customary to prepare a polyvalent scrum by injecting each horse with a large number of different varieties of streptococci. This serum, though not quite so efficient as if made by the strep- tococcus infecting each ease, will be fairly efficacious in all cases. As already mentioned, the results so far from the use of the antistreptococcus serum, therapeutically, have been somewhat variable. In some cases the disease has progressed in spite of large injections. In other cases apparent improve- ment has been noticed. With the exception of rashes. no deleterious effects have been observed, although in very large doses albuminous urine, for a short time, has followed. Thus the serum is certainly worth trying in suitable cases, even though no very striking results are to be expected. Care should be taken, however, to get the most reliable preparation, as much on the market is worthless. Full doses (30-50 c.c.) of serum should be given if the case is at all serious. Intravenous injections seem to give better results than those administered subcutancously. The following varieties of streptococci have been described by some authors: Streptococcus Brevis. — Develops in bouillon slightly curved, short chains; the bouillon is clouded. Gelatin is liquefied immediately around the colonies. There is a distinctly visible growth on potato. Grows at 10° to 12° C. Is usually non-virulent. Streptococcus Lonous. — Develops in bouillon long twisted chains, with a granular or flocculent sediment, the supernatant liquid remaining clear. Gelatin is not liquefied. There is no visible growth on potato. No growth under 14° to 1G° C. Is usu- ally highly virulent. The following subdivisions of this streptococcus have also been described: (1) Streptococcus turbidus with clouded bouillon culture; (2) Streptococcus vis- cosus with clear bouillon culture and slimy sediment; (3) Streptococcus conglomeratus with clear bouillon culture and granular sediment. The Pneumococcus (Micrococcus Lanceolatus; Diplococcus Pneumonia). — This micrococcus was first observed by Sternberg, and almost simultaneously by Pasteur (18S0), in the blood of rabbits inoculated from human saliva. It was subsequently described by Talamon (1SS3) and demonstrated by him to be capable of producing fibrinous pneumonia in rabbits when introduced directly into the lung of these animals. In 1885-1886 this microorganism was sub- jected to an extended series of investigations by Fraenkel, Weichselbaum, Sternberg, and others, and proved to be the chief cause of lobar or croupous pneumonic in man. Several dial incl varietii pneumococci have been recognized, showing quit a wide range of variation in morphology I'lie -c, called Strep In, 0i - . m < U (Schottmuller) and other capsulated chain bacteria, formerly classed as streptococci, e i red to be varieties of the pneum Besides the different varieties of pnei :occi the following bacteria are capable of exciting pneu ma: Streptococcic pyogen, , Stap) ,' . , , , Bacil- lus pneumonia}, Bacfflu ftuei BaciUus diphtherial, Bacillus typhi, Bacillus colt, Bacillus lulu rculosis. Microscopical Appearances. — Very irregular; oci typically as spherical or oval and lancet- taped » i usually united in pairs (diplococci), but sometimes as short chains consisting of four to six clem and resembling streptococci. In stained specimens from sputum, the fibrinous exudates of croupous pneumonia, the blood of inoculated animal-, ami cul- tures on blood serum, the lancet-shaped cells are com- monly surrounded by a gelatinous capsule. Varia- tion in form and arrangement is characteristic of the pneumococcus, then? being great differences according to the source from which it is obtained. (See Plate IX., Figs. 5 and 6.) Motility. — Non-motile. Staining Reactions. — Stains readily with ordinary aniline dyes; is not decolorized by Gram's solution. The capsule may be demonstrated in cover-glass preparations either by Gram's or Welch's (glacial acetic acid) method. Biological Characters. — Aerobic and facultative anaerobic, grows equally well in the presence and absence of oxygen. It develops on almost all culture media having a slightly alkaline reaction; but the growth is slow and scanty, and the virulence and power of reproduction are soon lost. Grows very slowly, often not at all at room temperature; opti- mum 37° C, maximum 42° C. Growth on Gelatin. — The growth on this medium is slow, often none at all, owing to the low temperature (22° to 25° C.) at which gelatin has to be kept. The gelatin is not liquefied. Groioth on Agar and Blood Scrum.- — At the end of forty-eight hours in the incubator, there appears on agar a thin colorless layer of non-confluent colonies. If blood serum or ascitic fluid be added to the agar the colonies are larger and closer together, the growth being more luxuriant. The growth of Loef- fler's blood-serum mixture is very similar to that on agar, but is somewhat more vigorous, appearing on the surface as small, fairly granular dew-drop-like colonies. Grouih in Bouillon. — At the end of twelve to twenty-four hours in the incubator a slight clouding is produced, due to the development of the organisms, which on microscopical examination are seen to consist of pairs or longer and shorter chains. After two or three days the medium again becomes trans- parent, the cocci sinking to the bottom of the tube. The best fluid medium for the cultivation of the pneu- mococcus is a mixture composed of bouillon two parts and ascitic or pleuritic fluid one part. In this medium the organisms grow well, and cultures kept in a cool place and prevented from drying retain their vitality for a number of months. Milk is a favorable medium, and in some cases coagulation takes place. Vitality. — In cultures the pneumococcus soon loses its vitality; it lives longest in media containing blood or serum. Pneumonic sputum attached to cloths, air-dried and exposed to diffuse daylight, retained its virulence for rabbits for periods of nineteen and fifty-five days in different experiments. Exposed to direct sunlight the same material retained its 861 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES virulence after twelve hours' exposure (Bordoni- Uffreduzzi). This resistance of the organism for so long a time under these conditions is attributed in part to the protective influence afforded by the albuminous envelope surrounding the micrococci in the sputum. Chemical Effects. — Three varieties of pneumococci have been isolated which produce a brick-red pig- ment. Filtered and dead unfiltered cultures contain toxins as products of growth. For other chemical effects, see Streptococcus. Pathogenesis. — The pneumococcus is quite patho- genic for some animals, especially mice and rabbits; rats are less susceptible, and guinea-pigs, sheep, dogs, and birds are almost immune. In mice and rabbits the subcutaneous injection of small quantities of pneumonic sputum in the early stages of the disease, or of a pure, virulent culture of the micrococcus, usually results in the death of these animals in from twenty-four to forty-eight hours. The course of the disease produced and the post-mortem appearances indicate that it is a typical form of septicemia — so- called sputum septicemia. The most marked patho- logical lesion is the enlargement of the spleen. The blood after death often contains large numbers of pneumococci. True localized pneumonia does not usually result from subcutaneous injections into susceptible animals, but injections made through the thoracic walls into the substance of the lung may induce a typical fibrous pneumonia. Attenuated cultures produce, according to the point of inocula- tion, pneumonia and pleurisy, peritonitis, etc. Atten- uation of the virulence of cultures of the pneumococ- cus may be produced artificially by the action of heat or several days' growth in the incubator, by continued Eassage through unsusceptible animals (guinea-pigs), y cultivation in unsuitable media, etc. Virulence is restored and increased by passage through highly susceptible animals of the same species from which the organism was originally obtained. The pneumococcus has not been found outside the body, except in sputum. It is frequently present in the saliva of healthy individuals. In diseased per- sons it is one of the most important pathogenic bac- teria. It is associated with various inflammatory Erocesses, especially of the mucous and serous mem- ranes; and is the chief etiological factor in the pro- duction of lobar and catarrhal pneumonia, pleurisy, pericarditis, endocarditis, empyema, peritonitis, otitis, meningitis, conjunctivitis, and keratitis; less fre- quently of nephritis, parotitis, metritis, pyosalpinx, strumitis, amygdalitis, arthritis, osteomyelitis, perio- stitis, etc., abscesses, and general septicemia. Erysio- elas can also be caused by it. In many of these aii :c- tions the organism is found not only locally, but also in the blood. Very often the pneumococcus is asso- ciated with and acts as a synergist of other pus- producers, as the staphylococcus, streptococcus, etc. It is carried from its original seat in the lungs to distant organs of the body by means of the circula- tion, being often found in the lymphatios and the blood both during life and after death. Knowing that the saliva and nasal secretions under normal conditions so frequently afford a resting place for the pneumococci, we have only to assume the pro- duction of a suitable medium for these parasites in the body, brought about by an abnormal condition of the mucous membranes from exposure to cold, or a reduction of the vital resistance of the tissue cells in an interior organ, by disease, traumatism, excesses of various kinds, alcoholism, etc., readily to com- prehend how an individual may become infected primarily or secondarily with pneumonia. Immunity. — Fraenkel has shown that subcutane- ous injections of rabbits with virulent cultures of the pneumococcus produced infection in only a small proportion of them; those which recovered were 862 found to be somewhat immune to a second infection. Artificially attenuated cultures or material containing naturally weakened micrococci have also been used for inoculation. Another series of experiments were based on the assumption that the protective sub- stances are contained in the natural or artificial products of the growth of the organisms. Thus cul- tures freed from bacteria by filtration and emulsions of pneumonic sputum, portions of pneumonic lung pleuritic exudates, etc., were employed for inoculation by different experimenters. But the quantity of material required for inoculation by these methods having been found inconveniently large, attempts have been made to obtain the immunizing products in a more concentrated form. Foa and Scabia, and the Klemperer brothers prepared glycerin extracts, after the manner of Koch's tuberculin, calling their product "pneumotoxin." At present, however, a protective serum is obtained from horses by the repeated injections of fully virulent pneumococci in exactly the same way as in the production of anti- streptococcus or diphtheritic antitoxic serum. Curative experiments in man have been recently made with this antipneumococcus serum obtained from immunized animals. The most successful of these were conducted by the Klemperers. They hold that in man during the pneumonic process there is a constant absorption into the circulation of the toxic substances produced by the bacteria. This contin- ues until eventually the same antitoxic substance is produced naturally in the body as is seen to occur experimentally. It is then, they think, that the crisis takes place. The bacteria are neither destroyed nor is their power to produce pneumotoxin lessened; but the third factor, the antitoxin, now exists and neutralizes the toxin. These authors state that they have been able to show that the blood serum of patients after the crisis contains antitoxic substances, and is capable, in a fair number of cases, of curing the disease when injected into infected animals. They have also made observations upon patients with a view of inducing the crisis by the injection of the blood serum of immunized animals and of persons convalescent from pneumonia. Somewhat favorable results have been reported in a certain number of cases thus treated by the Klemperers, Jansen, De Rienzi, Weisbacker, Washburn, Pass£, Ugheti, Mennes, Lambert, and others, but nothing definite so far has been accomplished. It may, therefore, be concluded that the curative treatment by antipneumococcus serum, like that of antistreptococcus serum, is still in the experimental stage. All that can be said about the results obtained is that the cases treated have, as a rule, done better than was expected, though no striking curative effects have been pro- duced. In many instances there was no develop- ment of pneumococcus blood infection; and even if the serum does not hasten the crisis and bring about a positive cure, yet it may be able to prevent a general infection. It is known that there are several varieties of the pneumococcus, as of the streptococcus, possessing different biological and pathological properties and varying virulence. Possibly it may be found that pneumococcus serum obtained from animals immunized against a certain variety of pneumococcus protects only fully against that variety, as with the streptococcus serum, and that large intra- venous injections of 50 c.c. of a polyvalent serum may be of value. But whether that be so or not, the injections, at any rate, of the serum have been shown to be practically harmless, and the benefits to be derived from the discovery of a curative remedy for pneumonia are so great that these experiments are certainly worth continuing. The Meningococcus (Diplococcus intracclhrfaris meningitidis). — This organism was isolated by Hill I'.IM'.XCK HANDlsniiK < >F Till: MFIHCAL SCIENCES Bacteria Weichselbaum (1887) from the exudate of cerebro- spinal meningitis, both when complicating pneumonia unci in uncomplicated cases, and from its usual pres- ence in the interior of pus cells he called it D acellularis. It has since been found (1895) by Jager and Schcurer in the nasal secretions and sputum ol persons suffering from tins affection during an epidemic. The frequency of its occurrence in and restriction to this disease afford sufficient evidence of its being concerned at times, at least, in the production of cerebrospinal meningitis, though the pneumococcus is probably the most common cause. Motility. — Non-mo! ile. Staining Reactions. — Stains with the ordinary aniline colors, but best with Loeffier's alkaline methyl- blue. It is readily decolorized by Gram's solution. Microscopical Appearances. — Occurs as coffec- i-shaped micrococci usually united in pairs (diplococci), but also in groups of four, and in small masses; sometimes solitary and smaller apparently degenerated forms are found. It has no well-defined ule. In the exudate it is generally found, like the gonococcus, to which it bears a close resemblance morphologically, in the interior of the pus cells and extranuclear. According to some authors it is sometimes indistinguishable in form from the pneu- mococcus, streptococcus pyogenes, and tetracoccus. Plate IX., Fig. S.) Biological Characters. — The meningococcus does not grow at room temperature but only between 25° and 40° C, best in the incubator at 3G°-37° C. Its devel- opment is usually scanty on the surface of agar, though sometimes a few colonies grow luxuriantly. It does not grow at all or very poorly in bouillon or bouillon mixed with one-third blood serum. It develops best on Loeffier's blood-serum mixture as used for diphtheria cultures. When grown on nutrient or glycerin agar, at the end of forty-eight hours in the incubator a tolerably good growth develops, appearing as flat, grayish colonies, viscid and usually non-confluent. On Loeffier's blood serum the growth forms round, whitish, shining, viscid-looking colonies, with smooth, sharply defined outlines. The colonies tend to become confluent, but do not liquefy the serum. Cultivated in artificial media the meningococcus soon loses its vitality (in six days), and must therefore be transplanted every two or three days to fresh media. Pathogenesis. — Not very pathogenic for animals; most for mice and guinea-pigs, less so for rabbits and dogs. Subcutaneous injections of animals give nega- tive results; intrapleural or intraperitoneal inocula- tions in mice and guinea-pigs, in large doses, are generally successful. The animals usually fall sick and die within thirty-six to forty-eight hours, showing slight fibropurulent exudation. In the blood and enlarged spleen diplococci are found in small numbers and mostly free; in the pleuritic exudate they are present in considerable quantities and then are found in the interior of the pus cells. Meningitis, corre- sponding to the disease as occurring in man, has been artificially produced in dogs by subdural inocula- tions of recent cultures. Under natural conditions in the human subject the meningococci probably gain access to the brain and meninges by way of the nose, ear, and upper air passages. They have been found not only in menin- geal pus but also in the nasal mucous secretions, the sputum, and the urine of patients suffering from meningitis, and occasionally in the nares of healthy persons coming in contact with patients. A mixed infection of the meningococcus, pneumococcus, and streptococcus pyogenes is often met with. Serum Treatment. — Numerous experiments, having for their object the production of a protective serum for this di been made since 1905 by variou investigators; Kolle and \\ . , Park, Joch- mann, I lexner, and others. The Bu use of an immune serum in cases of human cerebro- spinal meningitis, however, by the intraspinal method, may properly be accredited fo Jochmann and physicians who employed bis serum in 1005 and I This serum wa pr injecting hoi increasing doses of meningococcus, killed al about 58° C. The doses were given every eight d; beginning with a loopful and increasing until the growth on the surface of ascitic agar covering two Petri dishes was used. After this do ched living cultures were given. The serum a to possess both bactericidal and opsonic power. Forty were reported treated, but detail- were given of only seventeen patient-, five of whom died and twelve recovered, a tahty of 29 per cent. Joch- mann directed that after lumbar puncture, 20 to .">0 c.c. of fluid should be removed and then 2(J of immune serum injected. These injections were to be repea or twice if the fever did not abate or returned. A general betterment of the headache, stiffness of neck, and mental condition was noticed. Although the serum prepared in different labora- tories in Europe was regularly used after Jochmann's report, it did not receive much attention in this country until Flexner, at the Rockefeller Institute for Mei Ih.i1 Research, through his important experiments on infected monkeys, which demonstrated the value of the intraspinal injection of the serum, aroused a general medical interest in the subject, shortly after this, Flexner and Jobling published their report, which fully corroborated the earlier results of Joch- mann. From a large number of eases of the disease, which have now been treated, in which the bacterio- logical diagnosis was made, it appears that the aver- age mortality at all ages was about 31.5 per cent., the highest mortality being 42.3 per cent, which occurred in the first two years of life. The mor- tality, however, at this age period, under the older mode of treatment, was formerly 90 per cent, and over. The best results have been obtained in the first-to-third day injections, the poorest after the seventh day. It would seem to be evident, therefore, that the intraspinal injections of antimeningococcus serum are of undoubted value in the majority of cases and should always be given — the sooner the better — not even waiting necessarily for a bacterio- logical examination to give the first injection. No ill effects have been observed from the use of the serum. A bacteriological diagnosis of cerebrospinal menin- gitis may often be made by means of lumbar puncture to obtain a specimen of the fluid from the spinal canal, and microscopical examination and cultivation on Loeffier's blood serum. The clinical value of this is, that about forty per cent, of the cases due to the meningococcus recover, while almost all of those caused by the pneumococcus and streptococcus die. The Gonococcus (Micrococcus gonorrhoea;). — First observed by Neisser (1S79) in gonorrheal pus and described by him under the name of " gonococ- cus." It was obtained in pure culture by Bumm (1885), and its infective nature proved by inocula- tions into men. Microscopical Appearances. — Micrococci usually united in pairs (diplococci) or groups of four. The bodies of the diplococci are shaped like coffee beans or a Vienna roll, having an unstained division or interspace, in stained preparations, between two fiat surfaces facing one another. They are from 0.8 to 1.6 /i long and 0.6 to 0.8 /( broad. In gonorrheal discharges the diplococci are found mostly in small, irregular groups in or upon the pus cells and extra- nuclear. Occasionally round, single, and undivided 863 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cells are observed, and again irregular forms, parti- cularly in old cultures, and in chronic gonorrhea of long standing. (See Plate IX., Fig. 7.) Motility. — Non-motile. Staining Reactions. — Stains readily with the basic aniline dyes, especially with methyl violet, gentian violet, and fuehsin; not so quickly with methylene blue, which, however, is the best staining agent for demonstrating its presence in pus. The gonococcus is decolorized by Gram's solution, which enables it to be distinguished from other pus cocci; but this method cannot always be depended on to differen- tiate it from all diplococci found in the urethra and vulvovaginal tract, some of which are morpholog- ically similar to the gonococcus and are also decolor- ized by Gram's solution. Biological Characters. — Aerobic and facultative anaerobic. Does not grow at room temperature, best at 37° C. Growth on ordinary culture media is so scanty that special media have been devised for its cultivation. Human Placenta Serum Agar. — Wertheim has suc- ceeded in developing luxuriant and virulent cultures to many generations on a mixture consisting of pla- centa blood serum and two per cent, peptone agar. His method is as follows: Several loops of gonor- rheal pus are diffused through liquid placental blood serum warmed to 40° C. in a test tube. Two dilu- tions are made from this, and an equal quantity of melted two-per-cent. peptone agar cooled to 40° C. is added to the three tubes, and the contents poured into Petri dishes. At the end of twenty-four hours in the incubator there will have developed on at least one of the plates distinct colonies, which are in appearance translucent and finely granular with scalloped margins. By transferring such a colony to slant cultures of serum agar, pure cultures of the gonococcus are obtained; these are somewhat shiny in appearance and of a grayish-white color. Human Chest Serum Agar. — Heiman, and almost simultaneously, Kiefer and Menge, proposed a cul- ture medium made from hydrothorax, ascitic, or hydrocele fluid, obtained from the human subject. This medium as prepared by Heiman consists of a 2 per cent, agar +2 per cent, peptone +0.5 per cent, salt +2 per cent, glucose; of this mixture two parts are added to one part of "chest serum," obtained from a patient suffering from hydrothorax, acute pleurisy, or hydrocele, which, if necessary, is steril- ized. The chest serum agar should have a neutral reaction. The growth in this medium is thus de- scribed: "In plate cultures streaked on the surface, growth abundant, colonies circular in shape, edges somewhat irregular, shading off into yellowish-white; texture finely granular in periphery, presenting punc- tuated spots of higher refraction in and around the center of yellowish color." Pig Serum Nutrose Agar. — Wassermann recom- mends a culture medium for the gonococcus con- sisting of 15 c.c. pig serum diluted with 30-35 c.c. water, to which is added 2-3 c.c. glycerin, and finally about 2 per cent, nutrose (casein sodium phosphate). This is thoroughly mixed and boiled and sterilized by the fractional method. To the mixture is now added an equal quantity of 2 per cent, agar cooled to 40° O, for the inoculation of cultures, and then Eoured into Petri dishes. The growth is favored y admission of air, and is similar in appearance to that already described for plate and streak cultures. Toxins. — Wassermann has obtained on his serum nutrose agar virulent cultures of the gonococcus, which after being killed still possessed toxic action. The gonotoxin produced was found to be very resistant to heat and the action of alcohol; it killed mice, and in rabbits gave rise to caseous infiltration often passing into necrosis, and in large doses pro- 864 duced general toxemia. Injected into the human sub- ject the gonotoxin seemed to produce no curative effect on an existing chrome gonorrhea, the intense reaction caused not becoming less on repeated inoculations. The production of gonotoxin would seem to ac- count for the gonorrheal secretion. It also renders more comprehensible several obscure points in the history of chronic gonorrhea: for example, the fact that gonococci may be apparently absent from, or only isolated organisms present in, the gonorrheal discharge, and yet a purulent secretion be kept up containing few bacteria; but if, owing to some in- jury to the tissues, the organisms increase in number an acute exacerbation of the disease is again set up and masses of gonococci are then found in the pus. Vitality. — The gonococcus has but little resistant power against outside influences. It is killed by weak disinfecting solutions and by desiccation in thin layers. In comparatively thick layers, however, as when gonorrheal pus is smeared on linen, it has lived for forty-nine days, and dried on glass for twenty-nine days (Heiman). No development takes place below 25° C. or above 39° C; it is killed by a temperature over 42° C. Pathogenesis. — Gonorrhea as occurring in man is non-transmissible to dogs, monkeys, horses, and rab- bits, whether inoculations be made into the urethral, vaginal, or other mucous membranes. Large doses of virulent cultures produce in animals toxic inflam- mations, similar to that produced by the gonotoxin, without any multiplication of cocci. Although animal inoculations have been thus followed by negative results, the etiological relation of the gon- ococcus to human gonorrhea has been demonstrated beyond question by the infection of healthy men with the disease by inoculation of pure cultures by Bumm, Wertheim, Kiefer, and Heiman. The gonococcus has never been found outside the body, except in articles of clothing, etc., which have become contaminated by those affected with the disease; nor has it ever been met with in healthy per- sons. In those suffering from gonorrhea it has been found in the urethra and prostate of the male and in the urethra, vagina, and cervix uteri of the female, as the cause of the disease. Besides gonorrheal urethritis and vaginitis, the gonococcus is the cause of certain cases of endometritis, metritis, salpingitis, oophoritis, peritonitis, proctitis, cystitis, and prob- ably also of epididymitis; also of gonorrheal ophthalmia neonatorum, and rarely of diphtheritic conjunctivitis in children (Fraenkel). The gonococ- cus produces in adults severe conjunctivitis, sel- dom rhinitis and otitis. It is frequently the cause of gonorrheal arthritis, also probably in some cases of pleuritis, malignant endocarditis, parotitis, peri- ostitis, and bursitis. In the local affection squamous epithelium pro- tects better than cylindrical epithelium. The para- site penetrates gradually through the epithelium into the connective tissue. In travelling to distant organs of the body the gonococcus follows mainly the course of the lymphatics and produces inflammation which finally leads to fibrinous hypertrophy — stricture of the urethra, hypertrophy of the prostate, etc. There is no or very slight immunity produced after recovery from an infection. The use of sera in acute gonor- rheal joint inflammation has given in a considerable percentage of cases good results and seems to be worth trying. Vaccines (heated cultures) have also been used with apparently real benefit in joint inflam- mations and even in very localized chronic infections of the urethra, bladder, and elsewhere. The dose is from twenty to a thousand million given every three to seven days. There is practically no limit to the time during which a man or woman may remain infected with gonococci and infect others. A case has been under observa- EXPLANATION OF PLATE IX. EXPLANATION OF PLATE IX. Fig. 1. — Bacillus Coli Communis. Agar culture. Stained with fuchsin. X 1,000. Photomicrography from Bowhill's "Bacteriology" by permission. Fig. 2. — Streptococcus Pyogenes (Longus). X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. 3. — Staphylococcus Pyogenes Aureus. X 1,000. Photomicrograph from Park's " Bacteriology" by permission. Fig. 4. — Micrococcus Tetragenus (Tetracoccus). X 1,000. Photomicrograph from Park's " Bacteriology" by permission. Fig. 5. — Diplococcus Pneumoniae (Fraenkel) in Sputum, x 1.000. Stained by Gram's method. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. 6. — Diplococcus Pneumonias (Fraenkel) in Blood. X 1,000. Photomicrograph from Sternberg's "Bacteriology" by permission. Fig. 7. — Micrococcus Gonorrhoeae (Gonococcus of Neisser) in Urethral Pus. Stained with Loeffler's solution of methylene blue. X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. S. — Diplococcus Intracellularis Meningitidis (Meningococcus). X 1,000. Photo- micrograph from Park's " Bacteriology" by permission. Refekence Handbook OF THE Mf.dical Sciences Plate IX Streptococcus pyogenes. *?•.**•••*<' VII. Gonococcus (Neisser). vS- 1 V. Diplococcus pneumoniae in sputum. 9. #' in. Staphylococcus pyogenes aureus Pathogenic Bacteria. VIII. I liplocoocus intracellularis meningitidis. REFEHKNCF HANDBOOK OK Till' MEDICAL SCIENCES Bacteria ion where twenty years luul elapsed since exposure (i infect inn and yet the gonococci were still abundant. It is now well established thai most of the inflam- mations nf the female genital tract are due to gono- rncci and the majority of such infeel ions are produced in innocent women by their husbands who are suf faring from latent gonorrhea. In view of t lie fact i hat several non-specific forms of urethritis exist, and also that diplococci morpholog- ically similar to the gonococcus Neisser are often found in the normal urethra ami vulvovaginal tract, it becomes a matter of great importance to he able to detect gonococci when present and to differentiate these from the non-specific organisms. For the dem- onstration of gonococci, they must be found as diplococci lying in masses in the pus cells anil extra- nuclear, when stained with methylene blue and decolorized by Oram's solution. Organisms having these characteristics microscopically may for all practical purposes be considered as certainly gono- cocci, if they are obtained from the urethral discharge and confirmed by examination on three' successive days. But if there still remains any doubt, and especially if the organisms are obtained from the vulvovaginal tract, plate cultures should be made on one of the special media described (chest serum agar, etc.), on at least three consecutive days. Malta Fever (The Micrococcus rnelitensis). — This organism was first discovered by Bruce in Malta in 1887. The disease is confined to the shores of the Mediteranean, but cases have been observed in Porto Rico, China, Japan, and the Philippines. It does not seem to be directly transmitted from person to person. Prodromal symptoms follow an incubation period of 5 to 14 days. Headache, sleeplessness, loss of appetite, and vomiting accompany a high fever. The spleen and liver are enlarged. Neuralgic pains are severe. The fatal cases appear similar to severe cases of typhoid fever. Micrococci are found abun- dantly in the blood and all organs. Microscopical Appearances. — Very small rounded or slightly oval organisms, about 0.3 a in their greatest diameter. It is usually single or in pairs. In old cultures involution forms occur, almost bacillary in shape. Motility. — Absent. Staining. — It stains readily with aniline dyes and is negative to Gram. Biological Characters. — Grows rather feebly at 37° C. on nutrient gelatine and in broth. The colonies are not usually visible until the third day. They appear as small round disks, slightly raised with a yellowish tint in the center. The broth is slightly clouded after five or six days. The culture remains alive for several weeks or months. In gelatin the growth is very slow. Gelatin is not liquefied. Pathogenesis. — Among animals, monkeys only are infected. They pass through the disease much like man. They can be infected by subcutaneous or mu- cous inoculation. In Malta it has been found that about half of the goats pass organisms in feces, and so contaminate their milk, which is believed to be a source of infection. By safeguarding the milk the disease has been largely eliminated. Infections of heated cultures have been thought to give good results in treatment. Diagnosis. — The diagnosis of Malta fever can fre- quently only be made by bacteriological methods. Cultures are made by spreading over the surface of a number of agar plates freshly drawn blood. Often no organisms develop. The agglutination test is then required. The blood of persons suffering from other infections frequently agglutinates the micrococcus of Malta fever in low dilution, so that 1:500 or over is required for a positive diagnosis. Animals injected with the coccus produce a serum agglutinating in high dilution and this method can sometimes be used, under suitable precaution . to identify suspected cull un . The Bacillus of Soft Chan< Ducrey' hoc- ill" i. — This bacillus was first specifically and obtained in pure culture by Ducrey in Iss'J. An experimental inoculation is followed iii one or two days by a small pustule. This soon rupl and a small round depressed ulcer is lefl . Aboul this other pustules develop which tend to become con- fluent. The base of the ulcer is covered with a gray exudate and its edges are undermined. There i no induration as in the Byphilitic chancre. The secre- tion is seropurulenl and very infectio Microscopical Appearances. — About 1.6 p long and o.l fi thick, growing often in chains, sometimes twisted together in dense masses. Staining. — It stains best with carbol-fuchsin, and shows polar staining. Biological ammeters. — Grows best in blood-agar 1 1 \\o pails agar liquefied at 50° C. and mixed with one part human, dog, or rabbit blood) or in condensation water of blood-agar, at 35" to 37° C. It grows also in coagulated rabbit blood. In 24 to 48 hours, on the surface of the media, well-developed, shiny, grayish colonies, about 1 mm. in diameter, may be observed. The calonies remain separate, but only become numerous after further transplantation. The best results are obtained when the pus is taken close to the walls of the abscess. Glass smears show iso- late,! bacilli or short parallel chains with distinct polar staining. The organisms are especially char- acteristic in the water of condensation from' blood- agar, the bacilli being thinner and shorter, with rounded ends; sometimes long, wavy chains are found. After the eleventh generation of the culture, and upon all old cultures, on inoculation the character- istic soft chancre is produced in man. The bacillus lives several weeks in blood-agar at 37° C. but it soon dies in coagulated serum. All other ordinary culture media so far tried have given negative results and even with the media described development is difficult and often fails. The chancroid bacillus possesses but little resistance to deleterious outside influences. Hence the antiseptic bandages, etc., used in treatment of the affection soon bring about recovery by preventing the spread of the infection. The Bacillus Pyocyaneus (Bacillus of green and blue pus). — This bacillus is found in green or blue colored pus which occasionally accompanies the discharges from open wounds, and is the cause of the pigmentation produced. It was first obtained in pure culture by Gessard. Microscopical Appearances. — Delicate, slender rods, about 0.4 u broad and 1.5 to G /( long, often united in pairs or in chains of four to six elements, and occa- sionally growing into long threads. Motility. — Actively motile, possessing only one flagellum. Spore Formation. — Absent. Staining Reactions. — Stains readily with the ordi- nary aniline colors; does not stain with Gram's method. Biological Characters. — Aerobic and facultative anaerobic, but produces pigment only in the presence of oxygen. Grows readily on all artificial culture media at room temperature, but best at 37° C. On gelatin plates flat, irregular colonies with radiating borders are rapidly developed, imparting to the medium a fluorescent green color; liquefaction begins at the end of two or three days, and in five days the gelatin is completely' liquefied. In gelatin stab cul- tures liquefaction takes place rapidly at first near the surface and gradually extends downward; a greenish color is produced in that portion in contact with the air. On agar plates a wrinkled, moist, whitish layer Vol. I.— 55 865 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES is developed, the surrounding medium being at first bright green, later darker in color, and finally blue green or almost black. In bouillon a green fluores- cence is produced, the medium being clouded, and a floceulent sediment forms. Milk is coagulated and peptonized. On potatoes a greenish-yellow or brown- ish growth occurs, the surrounding surface being green. The Bacillus pyocyaneus produces two pigments — one of a fluorescent green (bacterio-fluorescin, soluble in water) and the other of a blue color (pyocyanin, soluble in chloroform) formed only in the presence of oxygen. A faint aromatic odor is produced in recent cultures; in old cultures a disagreeable ammoniacal odor. No indol or I-LS is formed by this bacillus, and very little acid from grape sugar; no gas. Nitrates and nitrites are converted into free nitrogen. The bacillus pyocyaneus produces poisons by its growth. It has but little resistance to outside influences. Drying kills it rapidly; exposure to the action of direct sunlight for four hours partly destroys its power of producing pigment. Pathogenesis. — Pathogenic for rabbits and guinea- pigs. Subcutaneous or intraperitoneal injections of 1 c.c. of a bouillon culture cause the death of these animals in from twenty-four to thirty-six hours, with the production of extensive inflammatory edema and purulent infiltration of the tissues. The bacilli multiply in the body, and may be found in the serous or purulent fluid as well as in the blood and organs. Smaller amounts do not kill the animals, but render them immune to doses fatal to those not thus immunized. In rabbits inoculated with a culture of the bacillus anthracis a fatal result may be prevented by soon after inoculating the animal with a pure culture of the Bacillus pyocyaneus. It has been suggested that the protective action is due to the chemical products of the growth of the bacillus, and not to an antagonistic effect of the living bacteria. Though widely distributed in nature, the bacillus f>yocyaneus has not so far been found outside the iving body. It has been observed occasionally in the mouth and intestines of healthy individuals, on the unbroken skin and in the purulent discharges of open wounds, also in bandages and dressings, at times epidemically in hospitals. Usually the organism appears only in association with the common pus cocci, coloring the pus blue or green. In some cases, however, it has been found alone in disease processes, as in otitis media, ophthalmia, bronchopneumonia, pericarditis, etc., especially in children, so that we have reason to believe that this bacillus, although ordinarily non-pathogenic for man, may under certain conditions become a source of infection. In general its presence in wounds delays the process of repair and may give rise to a depression of the vital powers from the absorption of its toxic products. The Bacillus Proteus Vulgaris. — This is the most important of a group of similar bacteria, known as the "Proteus group," which are among the com- monest and most widely distributed putrefactive organisms. They were formerly included by the earlier observers under the name of "Bacterium termo," which they applied to all minute motile organisms found in putrefying substances. It was discovered by Hauser in 1885. Microscopical Appearances. — Small, slender rods varying greatly in size, but on the average about 0.6 /t broad and 1.2 /x long, generally occurring in pairs but sometimes arranged in filaments, which may be more or less twisted. It is to its great vari- ability in form that it was given the name of proteus. Motility. — Actively motile. Spore Formation. — Absent. Staining Reactions. — Stains readily with aniline dyes, especially fuchsin or gentian violet; also stains with Gram's solution. Biological Characters. — Aerobic and facultative anaerobic. Grows on almost all culture media developing most rapidly at room temperature, but also in the ice box and in the incubator. Toxin production seems to be favored by admission of air. The growth on gelatin plates containing five per cent, of gelatin is very characteristic. At the end of ten to twelve hours at room temperature, small, round yellowish colonies with thick centers and irregular edges develop, from which brush-like offshoots are thrown out. Other colonies are surrounded by a zone of threads which, partly in circular, partly in irregular twisted figures, surround the central opaque mass. Straight and twisted offshoots, which fre- quently become detached from the parent colony, grow into the surrounding medium and continue moving about in the liquefied gelatin, sometimes called "swarming islands." When the consistency of the medium is more solid, as in ten-per-cent. gelatin, the liquefaction and migration of these sur- face colonies are more or less, retarded. In gelatin stab cultures the growth is less characteristic — lique- faction takes place rapidly along the line of puncture, and soon the entire medium is liquefied. Upon nutrient agar a rapidly spreading, thin, moist, grayish- white coating appears, and migration of the colonies also occurs. Milk is coagulated with the production of acid. On potato a dirty grayish coating develops. Bouillon is uniformly clouded. Culture media containing albumin or gelatin are decomposed by the proteus vulgaris with the pro- duction of a disagreeable putrefactive odor and alkaline reaction. It produces gas and acid from carbohydrates, thus giving off no odor. It also- produces indol and H,S. Urea is decomposed into carbonate of ammonium. It forms toxins, which may be obtained by filtration of the cultures through porcelain. The proteus vulgaris possesses consider- able resistance toward chemical and thermic influ- ences, but is killed at 60° C. in half a minute. Pathogenesis. — This bacillus is pathogenic for rabbits and guinea-pigs when injected intravenously, intraperitoneally, or subcutaneously in large quan- tities, death of the animal being produced with symp- toms of intoxication. The effects are much more readily produced when other organisms, as the strep- tococcus, are introduced simultaneously into the body. Less virulent species of pathogenic bacteria (staphy- lococcus, streptococcus) also gain in virulence when they are injected along with living or dead proteus cultures. The proteus vulgaris is found very commonly out- side the body in putrid meat and other decaying substances, such as foul water, etc. It is found also in the digestive tract of healthy persons. In disease, it is the organism chiefly concerned in the production of cystitis with ammoniacal urine, either alone or in conjunction with the Bacillus coli communis, and is so an etiological factor in many other genito-urinary affections. The Urobacillus liauefaciens septicus of some authors is probably identical with the proteus vulgaris. Although this bacillus, however, occurs quite frequently, along with other bacteria in various diseases, it has seldom been positively shown to be the specific cause of infection. Booker, who has made extended investigations into the etiology of cholera infantum, concludes that the proteus vulgaris plays an important part in the production of this affection. He found the bacillus present in eighteen cases of cholera infantum examined by him, but not in the feces of healthy infants. Levy believes that in so-called "meat or sausage poisoning" bacteria of this group are chiefly concerned, and that the pathogenic effects are due to toxic products evolved during their development; though others attribute this affection to an anaerobic organism, the Bacillus botulinus of Van Ermengen, the symptoms being see, REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Ba< i' i i.i escribed as botulism. According lo .Jiigcr, certain irms of icterus accompanied with fever, pain in the mscles, and enlarged liver and spleen, known as Weil's disease," are produced by the proteus. hus il would seem that, though ordinarily a harm- 'SS parasite, the proteus vulgaris may at times .nine pathogenic to man. Considering the very ide distribution of t li i-s organism in nature, the onder is that with its poisonous properties so few iseases apparently are produced by it. The Bacillus op Malignant Edema (Bacillus dematis maligni). — This bacillus is widely dis- puted, being found in the superficial layers of the oil especially in garden earth, manure, filth of all inds, and house drains; also in the blood and intes- uies of animals, it was discovered by Pasteur 1877), and later carefully studied by Liborius and v.n-h. Microscopical Appearances. — Rather large rods, imilar morphologically to tetanus and symptomatic nthrax bacilli, but showing a greater tendency to out into long filaments; in size from 0.8 to 1 ft iroad and 2 to 10 ft long. Motility. — Motile, but not very actively so except he short forms, having three to twelve flagella 1 1 ached to the ends and sides of the rods. Spore Formation. — Forms spores generally in the niddle of the rods and oval in shape. Staining Reactions. — Stains readily with the ordin- iry aniline dyes, especially when obtained from the iniinal body; decolorized by Gram's method. Biological Characters. — Strictly anaerobic, growing n all the usual culture media in the absence of oxygen. Development takes place at room temperature, but nore rapidly and abundantly at 37° C. This bacillus grows on nutrient gelatin, but more ibundantly on glucose gelatin containing one to two >er cent, of glucose. Gas is formed and the gelatin s liquefied. On agar plates the colonies appear as dull, whitish mints, irregular in outline, and when examined under i low power they are seen to be composed of a thick network of threads radiating irregularly _ from the enter to the periphery. Blood serum is rapidly- liquefied, with the production of gas. Bouillon is louded from the formation of gas. Milk is not coagulated. Cultures of the bacillus of malignant edema give off a peculiar odor. Pathogenesis. — Especially pathogenic for mice, guinea-pigs, and rabbits, although horses, cats, dogs, goats, sheep, calves, pigs, chickens, and pigeons are also susceptible, and occasionally man. Cattle are immune. A small quantity of a pure culture sub- cutaneously injected into a susceptible animal gives rise to general hemorrhagic edema which extends over the entire surface of the abdomen and thorax and results in the death of the animal. There is no odor developed, and little, if any, gas. In infection with garden earth, owing to the presence of associated bacteria, gas is produced having a putrefactive odor. Malignant edema is chiefly confined to the domestic animals, but cases have also been reported in man. Infection takes place most readily when, as in the natural disease, other bacteria are simultaneously' introduced, such as B. proteus and B. prodigiosus. Animals which recover from malignant edema are subsequently immune. Artificial immunity may be induced in guinea-pigs by the injection of filtered bouillon cultures which have been previously ster- ilized. Bacillus Aerogenes Capsulatus. — Found by Welch in the blood-vessels of a patient suffering from aortic aneurysm; on autopsy made in cool weather eight hours after death, the vessels were observed to be full of gas. Since then it has been found in a number of other cases. These cases, as a rule, showed marked symptoms of delirium, rapid pulse, high temperature, and the develop m of emphysema and discoloration of the di eased area, or of abdominal distention when the peritoneal cavity was involved. Microscopical Appearand Straight or slightly curved rods, with rounded or somel quare-cut ends, somewhat thicker than the anthrax bacilli and varying in length, occasionally growing out into long threads. In the animal body, ami sometimes in cult ores, the bacilli are i in lo ed in a tin capsule. Motility. — Non-1 not ili'. ,Sjiori Formation. — Absent. Staining Reactions.- Stains with the ordinary aniline dyes and by < barn's method. Biological Characters. — Anaerobic, growing at room temperature, but more rapidly at '.'•' ('. in the usual culture media in the absence of oxygen, with production. Gelatin is not liquefied, but is gradually peptonized. On agar grayish-white colonies are developed in the form ol llattened spheres, oval or irregular masses, beset with hair-like projections. Bouillon is diffusely clouded, and a white sediment is formed. .I////,- is rapidly coagulated. Pathogenesis. — Usually non-pathogenic in healthy animals, although Dunham found that the bacillus taken freshly from human infection i- sometimes very virulent. When quantities up to 2.5 c.c. of fresh bouillon cultures are injected into the circula- tion of rabbits and the animals killed shortly after- ward, the bacilli develop rapidly with abundant formation of gas in the blood-vessels and organs, especially the liver. Welch suggests that in some cases in which death has been attributed to the entrance of air into the veins the gas found at autopsy may have been produced by this or some similar microorganism entering the circulation and develop- ing shortly before or after death. The bacillus had been found in the dust of hospital wards. The Anthrax Bacillus (Bacillus anthracis). — This organism is always present in the blood of ani- mals affected with anthrax or splenic fever, an acute disease very prevalent, in certain parts of Europe and Asia, among sheep and cattle. In this country it is comparatively rare. The disease also occurs in man as the result of infection, either through the skin, the intestines, or, in rare instances, through the lungs, in the form of external anthrax or malignant pustule, and internal anthrax or wool-sorter's disease. Those persons are most subject to infection who come in contact with animals, hides, wool, etc. Owing to the fact that anthrax was the first infec- tious disease which was shown to be caused by a specific microorganism, the study of this bacillus has probably contributed more to our general knowl- edge of bacteria than any other living organism. It was first observed by Pollender in 1S49 in the blood of animals affected with anthrax. In 1S63 Davaine showed by inoculation experiments that it was capable of producing the disease. Then finally in 1879, Pasteur, Koch, and others demonstrated that the bacillus could be isolated in pure cultures on artificial media, and that when susceptible animals were inoculated with portions of these cultures con- ditions similar to those found in the animal from which the original cultures were obtained were produced. Microscopical Appearances. — In the blood of ani- mals it occurs as large rods of variable size, from 1 to 1.2.5 ft broad and 3 to 10 ft or more long, often arranged in flexible filaments twisted and plaited together. In unstained specimens examined in the hanging drop the ends of the rods appear to be slightly rounded, while in stained preparations they seem to be square cut. Under a high magnification, especially in 867 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cultures, the ends are seen to be a trifle thicker than the body of the cell, and occasionally somewhat indented and concave, giving to the rods the appear- ance of joints of bamboo cane. At one time much stress was laid upon these morphological peculiar- ities as distinguishing marks of the anthrax bacillus; but it has been found that they are the effects of artificial cultivation, staining, etc., and not neces- sarily characteristic of the organism under all con- ditions. The bacilli, when obtained from the blood of affected animals and certain culture media (liquid blood serum), are enclosed in a capsule, which in stained preparations may be distinguished by its taking on a lighter stain than the rods themselves which it surrounds. (See Plate X., Fig. 1.) Motility. — Non-motile. Spore Formation. — Forms spores under aerobic conditions at temperatures from 12° C. up to 37° C. The spores are elliptical in shape and once or twice as long as broad; they first appear as small refractile granules distributed at regular intervals, one in each rod, and as the spores develop the mother cells become less and less distinct until they finally dis- appear altogether, the complete oval spore being set free by its dissolution. Spores are never formed in the living animal or in unopened carcasses, owing to lack of oxygen, but in slaughtered animals, bloody dung, etc., where the conditions necessary for their production exist. This fact is practically important with regard to the disposal of the carcasses of animals dead of anthrax. In fresh culture media the germina- tion of spores takes place in a few hours. In old cultures which have been repeatedly transplanted the power of spore formation is often spontaneously lost. Certain varieties of anthrax bacilli soon become asporogenous. All agencies which decrease the virulence of the bacilli (as, for instance, cultivation at 42° C.) act unfavorably upon the function of spore formation. (See Plate X., Fig. 2.) Staining Reactions. — Stains easily with the ordinary aniline colors, also by Gram's method. Vitality. — Anthrax bacilli free from spores retain their vitality in cultures for months, probably by spore production; in water they soon die; in the soil fresh anthrax blood is rendered germ free by exposure to sunlight in twelve to twenty-four hours. Accord- ing to Koch, when exposed to desiccation, anthrax bacilli retain their vitality only for five weeks; in dried blood they withstand a temperature of 92° C. for one and one-half hours, but in the presence of oxygen they are killed by exposure to light in nine hours and in a vacuum in eleven hours. Pickling fails to destroy anthrax bacilli in meat in fourteen days, but kills them after six weeks. They are rapidly destroyed by moist heat at 60° C. Exposed to cold from 1° to 24° C. the bacilli in agar cultures were destroyed for the most part in twelve days, and the few surviving organisms yielded colonies of dim- inished pathogenic action and power of liquefying gelatin. Dried anthrax spores retain their vitality inde- finitely; in a moist condition in water, earth, putrid spleen, etc., the spores have lived for one and one-half to two and one-half years. They also resist a com- paratively high temperature. Exposed to dry heat they require a temperature of 140° C. maintained for three hours to kill them, but in moist heat they are destroyed by a temperature of 100° C. in four minutes. Anthrax spores in a desiccated condition are killed by the action of direct sunlight in four hours, by diffuse daylight in several weeks. Biological Characters. — Aerobic and facultative anaerobic, growing best in the presence of oxygen but also in its absence. Under the latter condition, however, this bacillus no longer liquefies gelatin, and the presence of oxygen is absolutely necessary for the formation of spores. The anthrax bacillus grows rapidly on a variety of nutrient media at a temper ature from 14° to 43° C, but best at 37° C. Growth on Gelatin. — On gelatin plates small, white opaque colonies are developed on the surface at the end of. twenty-four to thirty-six hours at 24° C. while the deeper colonies are of a greenish color! Under a low power the colonies exhibit a charac- teristic appearance, consisting of a light-gray tangled mass of threads projecting beyond the edges in curly hair-like tufts, which have been likened to a Medusa's head. Liquefaction of the gelatin takes place in three or four da3's, a white pellicle floating on the surface. In gelatin stab cultures at the end of twelve to twenty-four hours a thick, white central thread appears along the line of puncture, from which other white threads and irregular projections radiate Eerpendicularly into the medium. After two days quefaction commences on the surface and gradually extends downward. On agar plates the growth is similar to that on gelatin and is equally characteristic, but the colonics are not so compact. At the end of twenty-four hours in the incubator a grayish-white coating is formed on the surface, which spreads rapidly and consists of masses of long threads matted together. In bouillon the growth is characterized by the formation of flucculent masses which sink as a seoi- nient to the bottom of the tube, leaving the liquid clear. Pathogenesis. — Especially pathogenic for mice, guinea-pigs, and rabbits, somewhat less for cattle and sheep (except the Algerian sheep, which are immune:, and considerably less for horses; rats, cats, dogs, chickens, pigeons, and frogs are but little susceptible. Man, though subject to local infection (malignant pustule) from accidental inoculation of wounds, and occasionally to intestinal or pulmonary infection (wool-sorter's disease) as the result of inoculation through dust charged with anthrax spores and the con- sumption of meat from anthrax animals, is not as susceptible to this disease as the lower animals. Subcutaneous injections in susceptible animals result in death in from one to three days. Little or no change can be observed at the point of inoculation, but the subcutaneous tissue for some distance over the abdomen and thorax is found to be edematous, with small ecchymoses scattered throughout theeldem- atous portion; the underlying muscles are pale in color. The intestinal viscera show no marked micro- scopical lesions, except the spleen, which is enlarged, soft, and dark colored. The liver may present the appearance of cloudy swelling. The lungs are red or pale red in color, while the heart is usually filled with blood. The anthrax bacillus produces in susceptible animals a true septicemia, and after death the capil- laries throughout the body always contain the bacilli in larger or smaller number. It is difficult to produce infection by the ingestion even of spores, but by inhalation it may be readily caused in animals. Infec- tion is most promptly brought about by introduction of the bacilli directly into the circulation, but inocula- tion by contact with the abraded skin may also pro- duce infection. Many theories have been advanced to account for the occurrence of intestinal anthrax in cattle and sheep, the form of the disease which is most common in these animals. It has been thought that infection was produced mainly by the eating of food contami- nated by anthrax spores derived originally from the bodies of affected animals; but, as we have seen, it is extremely difficult to cause infection in this way. By some authors it has been supposed to be a mias- matic infection and likened to malaria; and occur- ring as it does in the summer months and in low swampy places, there would seem to be a possible analogy in this respect between the two infections. But anthrax occurs in epidemics, being present at one time in a certain place and absent in another. Pas- 868 REFERENCE HANDBOOK OF THE MEDK \l. SI II W I - li. M terla ■ ur is of the opinion that the earth-worms play an uportant part in conveying the spines from one icality i" anotlier from the buried carcasses of af- :cted animals; but Koch has shown this hypothesis ) be untenable, as the bodies of earth-worms offer n unsuitable medium for the growth of spores, even ' they arc taken up and carried in this way. The lost plausible explanation so far suggested for the ilution of the problem is the supposition that under atural conditions unfavorable to the development f the bacilli an attenuation of their virulence takes ilace, and then again as the conditions become e favorable the virulence is restored — a result hich ran be artificially produced in cultures by bemieal agents, heat, etc. Nuttall has recently st d that perhaps the disease may be conveyed a the bodies of insects, under certain conditions, as it li malarial infection; but here, too, the bacilli indergo attenuation, according to the same author. nation of Virulence and Immunity. — The ,-irulence of anthrax cultures may be artificially tttenuated by the action of chemical agents and icat. Pasteur has succeeded in effecting considerable mmunity against anthrax in regions where this lisease is prevalent, by the inoculation of cattle and -heep with cultures attenuated by heat. Two vac- lines are employed of different degrees of strength, irepared from virulent cultures reduced in virulence by cultivation at temperatures between 42° and 43° According to statistics collected by Chamber- land from the results of twelve years' experience with this method of protective inoculation in France, out of three million sheep thus treated only one per cent. have died of anthrax since its introduction, whereas the mortality previously was over ten per cent. In cattle the mortality percentage has been reduced from five per cent, to 0.3 per cent. The method, however, is not unattended with danger, and some- times the animals succumb to the effects of the inoculation. The Bacillus of Symptomatic Anthrax. — Like the bacilli of anthrax, of malignant edema, and teta- nus, to all of which it bears a certain resemblance, the bacillus of symptomatic anthrax is an inhabitant of the soil. It is the specific cause of the disease in animals, principally cattle and sheep, known as "black-leg." "quarter-evil," or symptomatic anthrax, which prevails in certain localities, and is character- ized by a peculiar emphysematous swelling of the tissues of the leg and quarters, accompanied with the formation of gas. On section of the affected parts the muscles and cellular tissues are found saturated with bloody serum, while the tissues them- selves are dark, almost black in color. The bacillus can always be found in the affected parts, in the bile, and after death in the internal organs. Microscopical Appearances. — Long rods, with rounded ends, from 0.5 to 0.6 ,u broad and 3 to 5 n long; mostly isolated, also occurring in pairs, joined end to end, but never growing out into long filaments. as the anthrax bacillus does in culture media and the bacillus of malignant edema in the animal body. Motility. — Actively motile, flagella being attached to the bodies of the cells. Spore Formation. — Forms spores elliptical in shape, usually thicker than the bacilli, lying near the mid- dle of the rods, but rather toward one end, giving them a spindle shape. fining Reactions. — Stains with the ordinary aniline dyes, but not with Grain's method or only when the staining is much prolonged. Biological Characters. — Strictly anaerobic, growing only in the absence of oxygen, best in an atmosphere of hydrogen but not in CO,. Develops at room tem- perature in the usual culture media, but best in media containing 1.5 to 2 per cent, glucose or 5 per cent, glycerin and at 37° C. On gelatin, irregular, slightly tabulated colonies develop and the gelatin is -oon Liquefied. On ";/'"" the colonies are similar to those of malignant edema but somewhat more compact, after twenty-four to forty-eight hours in the incubator. In agar -tali ires growth occur- i ielow the sur- face, and is accompanied by the production of gas having a peculiar, disagreeable, rancid odor. Patho .—Pathogenic for cattle (which are im- against malignant edema), sheep, go guinea-pig-, and mice; less so for horse: and i i . pigs, cats, dogs, chickens, and pigeons arc, as a rule, immune. Infection lias never been pro- duced in man. When susceptible animals are inoculated Bubcu- taneously with pure cultures of this organism, with - or with bits of diseased tissue, death occurs in from twenty-four to thirty-six hours. At autopsy a bloody serum is found iii the subcutaneous tissues extending over the entire surface of the abdo- men, and the muscles present a dark red or black ap- pearance, even more intense in color than in malignant edema, and there is considerable development of gas. The ordinary manner of natural infection in cattle is by wounds which not only tear the skin, but pene- trate the subcutaneous tissues. The disease is also produced by the ingestion of forage contaminated by the bacilli or their spores, and by the inhalation of dust containing the organisms. Immunity. — It is well known to veterinarians that natural recovery from one attack of symptomatic anthrax protects an animal from a second attack. Artificial immunity can also be produced in various ways: by intravenous inoculation; or in guinea-pigs, by inoculations with bouillon cultures which have been kept for a few days and have lost some of their virulence, or with cultures kept in the incubator at 42° to 43° C; or by inoculations made into the end of the tail; or by injection of filtered cultures sterilized by heat. Arloing, Cornevin, and Thomas recom- mend for the production of immunity in cattle the use of a dried powder of the muscles of animals dead of the disease, which has been subjected to a tem- perature sufficient to attenuate its virulence. Two vaccines are prepared, as in anthrax one by exposure of the powder to 85°-90° C. (the stronger vaccine 1 , and the other to a temperature of 100°-104° C; the weaker vaccine is first used, and then the stronger. The inoculation is made into the cellular tissue of the ear or on the end of the tail; fourteen days are allowed to elapse between the two inoculations. Kitt recom- mends a single vaccine from infected flesh heated for six hours at 100° C. and given in decigram doses. The results obtained from these methods of prevent- ive inoculation against symtomatic anthrax would seem to have been fairly satisfactory. The Spirillum of Asiatic Cholera (Koch's comma bacillus). — In 1SS3 Koch isolated from the dejecta and intestines of patients suffering from Asiatic cholera a characteristically curved organism — the so-called "comma bacillus" — and showed that these bacteria were exclusively found in cases of the genuine disease. Other observers have since de- scribed morphologically similar organisms of non- choleraic origin. Finkler and Prior, for instance, observed such organisms in the diarrheal stools of patients with cholera nostras; Deneke found others in old cheese. .Miller met with others again in cari- ous teeth, and Metehnikoff observed others in fowls. But all of these organisms differ in many respects from Koch's comma bacillus, and none of them is affected by the specific serum of animals immunized to Asiatic cholera. Though varying somewhat in different epidemics, this spirillum is now generally recognized by bacteriologists to be the chief etio- logical factor in the production of true Asiatic cholera. Mi'.! Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Microscopical Appearances. — Curved rods, with rounded ends which do not lie in the same plane, from O.S to 2 /i in length and about 0.4 u in breadth. The curvature of the rod may be very slight, like a comma, but sometimes it forms a half-circle, or two contact rods curved in opposite directions may form an S-shaped figure, and under unfavorable con- ditions of growth, as in old cultures and on the addi- tion of chemical antiseptics, etc., they may develop into long spiral filaments consisting of numerous turns of a spiral in which it is impossible to recognize any connection between the individual elements of which they are composed. These latter, the true spirilla, are considered to be involution forms. Under favorable conditions of growth and in fresh cultures, the slightly curved or almost straight forms are com- monly observed. (See Plate X., Fig. 5.) Motility. — Actively motile, the movements being undulatory and due to one or two flagella attached to the ends of the rods. Spore Formation. — Absent; the arthrospores de- scribed by Hueppe have not been confirmed by other observers. Staining Reactions. — Stains with the ordinary anil- ine colors, but not as readily as many other bacteria; an aqueous solution of carbol fuchsin gives the best results with the application of heat. It is decolor- ized by Gram's method. Biological Characters. — Aerobic and facultative ana- erobic, growing on all the usual culture media at room temperature, but best in the presence of oxygen at 37° C. There is no development below 8° C. or above 42° C. The culture media must be distinctly alkaline, as the spirillum is very sensitive to acid. On gelatin plate cultures at 22° O, at the end of twenty-four hours, small, round, yellowish-white to yellow colonies may be seen in the depths of the me- dium, which later grow toward the surface and cause liquefaction of the gelatin, the colonies sinking to the bottom of the pockets thus formed. Examined under a low power they appear granular in structure with more or less irregular outlines, the surface looking as if covered with little fragments of glass. An ill-defined halo is first seen to surround the colo- nies, which has a peculiar reddish tint by transmitted light. In gelatin stab cultures at the end of twenty- four to thirty-six hours a small funnel-shaped depres- sion appears on the surface of the medium, which soon spreads out in the form of an air bubble above, while below this a whitish, viscid mass is seen. The funnel .now increases in depth and diameter, and in from four to six days may reach the edge of the tube; in from eight to fourteen days the upper two-thirds of the gelatin is liquefied; and in a few weeks com- plete liquefaction takes place. Upon agar plates the growth is not so character- istic, a moist, shining, grayish-yellow coating develop- ing on the surface in the incubator. Blood serum is rapidly liquefied at brood tempera- ture. In bouillon the growth is rapid and abundant, the liquid being diffusely clouded, and on the surface a wrinkled membranous film is often formed. On potato having an acid reaction no growth, as a rule, takes place; but if the potato be rendered alka- line with a solution of soda or cooked in a three-per- cent, solution of common salt, development takes place in the incubator as a thin, semi-transparent brown or grayish-brown layer. Milk is a favorable culture medium, but is not changed, as a rule, though it is coagulated by some varieties of cholera spirilla. Vitality. — The comma bacillus does not usually ex- hibit much resistance to outside influences. In pa- tients suffering from the disease the organisms have, as a rule, disappeared from the contents of the intes- tines in from four to eight, or more rarely in from ten to 870 fifteen days; though in a few cases living spirilla have been found after forty-seven days. They have been observed in cholera dejections for from one to three and occasionally from twenty to thirty days; in one recorded case after one hundred and twenty days. Even in cultures the spirilla of Asiatic cholera are rather short-lived. They have been found, however, to retain their vitality in pure bouillon cultures for three or four months and in agar cultures for six months or more, when protected from drying. I Q unsterilized water they may live for a considerable time apparently, though the observations on this vary from one day to one year. In sterile water they develop to some extent and retain their vitality for several weeks. Low temperatures, absence of light, and presence of salt in the medium would seem to favor their preservation. In well or river water they usually die in from three to eight day-. In food they retain their virulence for a period varying from a few hours to a few days. The comma bacilli are rapidly destroyed by desiccation. Exposed in cultures on a cover glass to the action of the air at room temperature they are killed in two or three hours unless spread in a very thick layer. This fact indicates that infection is probably not usually produced through dust or other dried objects contaminated with cholera bacilli. They are destroyed by moist heat at 60° C. in ten minutes. They resist cold fairly well, withstanding repeated freezing without being killed, though their growth is inhibited. They have but little resistance to the action of chemicals, especially mineral acids, which have thus been employed for the disinfection of waterworks to which these germs have gained access. For disinfection on a small scale 0.1 per cent, solution of bichloride of mercury or two to three per cent, solution of carbolic acid may be used. Milk of lime is a good general disinfectant on a large scale. The wash and linen of cholera patients, floors of dwellings, etc., may be disinfected by a five per cent, solution of carbolic acid and soap water. Chemical Effects. — The spirilla of cholera produce pigment in small amount only on potato. The peculiar disagreeable odor given off from cholera cultures in bouillon has been thought by some to be of diagnostic value, but it is not specific. Milk sugar is decomposed with the production of lactic acid without gas. In lactose-litmus agar the cholera spirillum forms on the surface of the medium a blue film, below this a red coloration, while lower down the medium is decolorized. When a small quantity of chemically pure sulphuric acid is added to a twenty-four-hour-old bouillon cul- ture of the cholera spirillum containing peptone, a red- dish-violet color is produced — known as the " nitroso- indol reaction" — which is due to the production of indol and the reduction of nitrates in the culture to nitrites. Brieger separated the pigment thus formed, called " cholera red." For a long time it was believed that the nitroso-indol reaction was peculiar to the cholera spirillum, and great weight was placed upon its production as a diagnostic test. But it has been shown that it is by no means specific, many other bacterial species giving the same reaction under similar conditions. The reaction, never- theless, is a constant and characteristic property of this bacillus, and is of undoubted value in differen- tiating this from other similar organisms which do not give the reaction. For the test it is best to employ a culture not of bouillon, but a distinctly alkaline solution of peptone (1 per cent, peptone + 0.5 per cent, sodium chloride — Dunham's solution), from which more constant results are obtained. Several toxins have been obtained from cholera cultures, but all of them much less poisonous than the original cultures. According to Pfeiffer these toxins are to be considered as secondary products i;i I i;i:i:\i i: nwiHionK <>r Tin: MKDIC'AL SCIENCES Bacteria modified by the action of the chemical reagents em- ployed in separating them. Very much more power- ful toxic products have ln.ii obtained from tin- bodies of the bacilli cultivated on agar and carefully killt d by chloroform or heat. Three times the minimal fatal dose thus obtained from an agar culture (about 0.5 ingiii.) kills a guinea-pig in from sixteen to eight- een hours, when injected into the peritoneal cavity. tin- effect being exactly t lie same as that produced by the living organisms, viz., rapidly beginning symptoms of the algid stage, muscular weakness, collapse, and death. Pathogt in six. — None of the lower animals being naturally subject to Asiatic cholera, there is little reason to expect that inoculations of pure cultures of the spirillum should give rise to typical cholera infection. It has been shown, moreover, that the comma bacillus is extremely sensitive to the action of acids, being quickly destroyed in the stomach by the acids of the gastric juice. Nevertheless, numer- ous attempts have been made to produce cholera in test animals by inoculation of pure cultures of the organism, usually with negative or unsatisfac- tory results. Koch, however, succeeded in producing an approximation, at least, to the symptoms of cholera in man by the infection of guinea-pigs by the following method: First, o c.c. of a five per cent. solution of sodium carbonate is injected into the stomach by means of a pharyngeal catheter, in order to neutralize the gastric contents; and then, after a while, 10 c.c. of a liquid containing one or two drops of a bouillon culture of the bacillus is administered in a similar manner, and at the same time the animal receives int raperitoneally 1 c.c. of laudanum per 200 gm. weight, to control the peristaltic movements. As the result of this treatment the animals are nar- cotized for about half an hour, but recover without showing any ill effects from the opium. _ In about twenty-four hours the temperature begins to fall, weakness and paralysis set in, and, as a rule, death occurs within forty-eight hours. On autopsy the intestines are found to be congested and filled with watery fluid containing large numbers of spirilla. Unfortunately, however, other morphologically simi- lar spirilla (the spirilla of Finkler-Prior, Deneke, and Miller) act very much in the same way, though somewhat less powerfully. Intraperitoneal injec- tions of large quantities of cholera cultures also often produce death in rabbits and mice with similar symptoms. With regard to the pathogenic properties of the cholera spirillum for man, there are quite a number of cases on record of accidental infection by pure cultures, which furnish the most satisfactory evidence of its being capable of producing the disease. In 1884 a student in Koch's laboratory in Berlin became ill with a severe attack of true Asiatic cholera while working with cholera cultures at a time when there was no cholera in Germany. In 1S92 Pettenkofer and Emmerich experimented on themselves by swallowing small quantities of fresh cholera cultures, with the result that both of them were taken, sick with typical cholera, one with mild and the other with severe symptoms. Since then other similar experiments have been reported, most of the persons taking the cultures having neutralized the acidity of the stomach previously by means of soda solution; and several fatal cases have occurred from accidental infection. At the same time, however, some negative results from experiments on the human subject have also been recorded — which only goes to show that in cholera, like other infectious diseases, an individual susceptibility is required, in addition to the presence of the germs, to produce infection. According to Pfeiffer, cholera in man is an infective process due to the destruction of the epithelial layers of the intestines by the spirilla and the products of their growth, whereby intoxication results from absorption of the poisonous i ' ' . The larger the surface of the mucous membrane affected, tie- more abundant will be the development of bacilli and the production Of toxins, and the more pro- ed, iu consequence, will be the intoxication. The cholera spirilla have been frequently found in water (wells, water pipes, rivers, harbors, etc.) which has become contaminated with the evacuations of cholera patients. Hut to prove their presence beyond question in water is by do means easy, as there are o many other water bacti ria imulating cholera bacilli from which they mii-i be differentiated; hence - e of the reported findings may not have been genuine cholera spirilla. The comma bacillus has been quite often observed in the feces of healthy per-.. us without producing, apparently, any pathogenic symptoms whatever. Abel and Claussen thus found cholera spirilla present in the stools, for days at a time, of fourteen out of seventeen healthy persons in the families of seven cholera patients. Jn Hamburg, during the last epidemic of cholera in Germany, twenty-eight such cases were observed in which the stools were absolutely normal. The cholera spirillum, however, has been found in no other disease than true Asiatic cholera, occurring in this affection chiefly in the contents of the intestinal canal and especially in the mucous flakes of so-called " nee-water" stools, existing in pure culture fre- quently, and usually present in greatest, numbers at the height of the attack. The spirilla are not, as a rule, found in the interior organs in recent cholera ca except perhaps occasionally in the intestinal glands. In rare instances, nevertheless, both in cholera patients and in inoculated animals, they have been met with in the organs — lungs, liver, kidneys, spleen and occasionally the heart's blood. The more virulent the organism is, the more apt, apparently, is it to gain access to the interior organs. Immunity. — Recovery from an attack of cholera produces a certain degree of immunity to the disease. Lazarus in 1S92 observed that the blood serum of persons who had recently had cholera possessed the power of protecting guinea-pigs from infection by the cholera spirillum; while the serum of healthy persons or those affected with other diseases had no such effect. He attributed this to the presence, in the serum of convalescents from cholera, of antitoxic substances which neutralized the action of the toxins produced by the growth of the spirilla, in the same manner as the antitoxins of diphtheria and tetanus neutralize their respective toxins. Pfeiffer, on the other hand, maintained that this serum contained bactericidal substances which killed the spirilla so rapidly when injected into the animal that they were not able to produce their specific poisons, and that thus the animal was protected. It is now generally admitted that the serum is strongly bactericidal and feebly antitoxic. These specific substances present in the blood of cholera-immune men and animals act only upon organisms similar to those with which they were originally infected — producing immobilization and agglutination of the bacilli. Pfeiffer, who first observed this peculiar reaction in cholera serum, has shown, however, that the specific relation existing between the antibacterial and protective substances produced during immunization and the bacteria employed to immunize the animals is not confined alone to cholera. This discovery has given us an apparently reliable means of distinguishing the cholera and typhoid bacilli especially from all other similar organisms, and the diseases which they produce from other infections which may be mistaken for them, which has proved to be of great practical value as an aid to clinical diagnosis. There are two methods, known as Pfeiffer 's and Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Gruber's reactions, whereby genuine cholera spirilla may be differentiated from other similar vibrios: 1. Pfeiffer's reaction is produced as follows: The blood serum of an animal rendered immune to cholera, by inoculation of attenuated or dead cholera cultures, is mixed with ordinary bouillon in the proportion of 1 to 100, and in 1 c.c. of this mixture a platinum loopful (about 2 mgm.) of the species under investiga- tion is added, and this then injected into the periton- eal cavity of a guinea-pig weighing about 200 gin. Every five minutes some of the peritoneal effusion is removed by means of a capillary pipette and examined microscopically both stained and unstained. If it is the true comma bacillus, the bacilli will be observed to become at first non-motile, then agglutinated into clumps, and finally (in about twenty minutes) to become disintegrated and loosened. When the above phenomena are absent, the organism belongs to another species. A control experiment should be made with a known cholera culture to avoid possible error. 2. Gruber's reaction is founded upon this, but he deserves the credit of having determined the amount of dilution required to agglutinate and immobilize the cholera spirilla when mixed with cholera-immune serum for microscopical examination in the hanging drop, without injection into guinea-pigs, thus simpli- fying the method for practical use. For this purpose the blood serum of a person suffering from a case of suspected cholera, or of an animal immunized against the species to be investigated, is mixed with a pure cholera culture in the proportion of 1 to 50 and upward, and the mixture at once examined in the hanging drop. If the spirilla become immobilized and agglutinated into clumps within twenty or thirty minutes, then they are genuine cholera spirilla; if not, the result is negative. Immunity. — Within the last few years Haffkine in India has succeeded in producing an artificial im- munity against cholera infection in man by means of subcutaneous injections of dead cultures of the cholera spirillum; and Nolle has found that the blood serum of persons thus inoculated gave a reaction similar to that of persons who had recovered from cholera, showing bactericidal and agglutinative substances from the fifth day, but most distinctly on the twentieth day and for months after the protective inoculation. In over 200,000 persons inoculated with Haffkines' vac- cine the results obtained would seem to show a distinct protective influence in the preventive inoculations. Spirilla Resembling the Spirillum Cholera Asiatic.e. — When Koch's comma bacillus was first discovered its properties seemed so characteristic that it was considered an easy matter to distinguish it from all other bacteria. Since then, however, more and more similar organisms have been met with by various investigators, until now they have ceased to be designated even by special names. The following are among the best-known species: 1. Spirillum or Finkler and Prior (Vibrio pro- teus). — This organism was obtained by Finkler and Prior from the dejections of patients with cholera nostras which had been allowed to stand for some days. It has since been found to bear no etiological relation to the disease, and is of interest only on account of its resemblance in some respects to the cholera spirillum. It occurs as more or less curved rods, usually some- what longer and thicker than the cholera spirilla and not so uniform in diameter. Involution forms are common in unfavorable culture media. It is actively motile, a single flagellum being attached to one cud of the rods. It does not form spores. (See Plate N., Fig. 6.) It grows equally well, in the presence and absence of oxygen, on the usual culture media at room temperature. On gelatin plates small, white, punc- tiform colonies are developed at the end of twenty- four hours, which under a low power are seen to be finely granular and yellowish in color; liquefaction of the gelatin around the colonies progresses rapidly and is usually complete in forty-eight hours. Isolated colonies on the second day form cup-shaped depres- sions. In stab cultures on gelatin liquefaction proceeds much more rapidly than with the cholera spirillum, a stocking-shaped pouch appearing in two days, while the entire gelatin is liquefied in about a week; a whitish film forms on the surface. Upon agar a moist, shining layer covering the entire surface is quickly developed. Blood serum is rapidly liquefied. On potato at room temperature a shining, grayish- yellow layer is formed, soon spreading over the surface. The cholera spirillum, on the other hand, produces no growth on potato at room temperature. The cultures of the Finkler-Prior spirillum give off a strong putrefactive odor; in media containing sugar they produce acid; they do not form indol, and they have a greater resistance to desiccation than the cholera spirilla. The absence of the agglutinative reaction with a dilution of the serum of an animal immunized to cholera is a valuable differential sign. This organism is pathogenic for guinea-pigs when introduced into the stomach after previous injection of soda solution and tincture of opium, similar symptoms being produced, only somewhat less marked, as with the cholera spirillum. Although originally observed in the dejections of persons affected with cholera nostras, it probably has no relation to this disease, having been seldom found since under such conditions by subsequent observers. 2. Miller's Spirillum. — In 1SS4 Miller observed a curved bacillus in dental caries which, from its microscopical appearances in cultures and from animal experiments, has been thought to be identical with the Finkler-Prior spirillum. The Vibrio helio- genes of Fischer and the Vibrio lisbonensis o/Pestana, and other similar spirilla met with from time to time, are also probably identical. 3. Deneke's Cheese Spirillum (Vibrio tyro- genes). — This organism was obtained by Deneke from old cheese, but has since been rarely observed. Morphologically and culturally it shows greater resemblance to Koch's comma bacillus than does the Finkler and Prior spirillum. It occurs in curved rods and long spiral filaments, the diameter of the segments being uniform throughout. On the other hand, it is somewhat more slender than the comma bacillus and the spiral turns are closer together. In its power of liquefying gelatin it stands between the cholera spirillum and the vibrio proteus, and its other char- acters are also so intermediary between these two species that they are scarce worth describing. It is said to form a thin, yellowish coating upon the surface of gelatin and agar stab cultures, and not to give the indol reaction; but these characteristics are not constant. The chief means of differentiating it from the cholera spirillum is by the serum reaction. 4. Spirillum Metchnikovi. — This spirillum was discovered by Gamaleia in 1SSS in the intestinal contents of fowls dying of an infectious disease com- mon to certain parts of Southern Russia, and pre- senting symptoms like those of fowl cholera. It has since been found by Pfeiffer in the waters of the Spree and by Kutcher in those of the Lahn. In the affected animals it is almost always found in the intestines, but also in the blood, producing septicemia. This interesting microorganism cannot be morphologically distinguished from the cholera spirillum; it occurs as curved rods somewhat thicker, shorter, and often EXPLANATION OF PLATE X. EXPLANATION OF PLATE X. Fig. 1. — Bacillus Anthracis from Cellular Tissue of Inoculated Mouse. Stained with gentian violet. X 1,000. Photomicrograph from Sternberg's "Bacteriology" by permission. Fig. 2. — Anthrax Spores from a Bouilion Culture. Double-stained preparation — with carbol-fuchsin and methylene blue. X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. 3. — Bacillus of Tetanus from an Agar Culture. X 1,000. Photomicrograph from Sternberg's " Bacteriology" by permission. Fig. 4. — Bacillus of Glanders. X 1,000. Photomicrograph from Sternberg's "Bacteri- ology" by permission. Fig. 5. — Spirillum of Asiatic Cholera (Comma Bacillus). From a culture upon starched linen at end of twenty-four hours, stained with fuchsin. X 1,000. Photomicrograph from Sternberg's "Bacteriology" by permission. Fig. 6. — Spirillum of Finkler and Prior with Flagella. Agar culture. X 1,000. Photo- micrograph from Bowhill's "Bacteriology" by permission. Fig. 7. — Bacillus of Bubonic Plague from Agar Culture, showing Irregular Forms. X 1,000. Photomicrograph. Fig. 8. — Bacillus of Bubonic Plague from Bouillon Culture, Showing Rods in Chains with Polar Staining. X 1,000. Photomicrograph. Reference Handbook OF THE Medical Sciences Plate X J ,- ■-■ Bacillus Anthracis VI. Spirillum Finklcr Prioi <-: . *x- Anthrax Bacillu with Spores V ,* 4, Cholera Spirillum III. Tetania Bacillus. VIII. Plague Bacillus. (Broth Culture) Pathogenic Bacteria. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria ,,, iv decidedly bent than the comma bacillus. It queues gelatin, as a rule, much more rapidly than he cholera bacillus does, but this varies. It gives lie nitroso-indol reaction without the addition of litrites, and coagulates milk with acid reaction. It [oes not give the serum reaction with cholera- mmune serum. The Spirillum mclchnikori is characterized by its >athogenic action for chickens and pigeons; a minute [uantity of a culture injected into the breasl muscles of hese animals causes their death with the local and gen- ;ral symptoms of fowl cholera, except thai I he contents )f the intestines have more the appearance of cholera md the spleen is rather diminished than enlarged. la the blood and edematous fluid about the necrotic loint of inoculation, the organisms are present in large iiumbers. Gamaleia has claimed that by passing the aolera spirillum of Koch through a series of pigeons, upon which this organism is said to act similarly to the Vibrio metchnikovi, by successive inoculations, its pathogenic power may be greatly increased, and thai when sterilized cultures of this virulent variety of bacillus are injected into pigeons they become immune to the Vibrio metchnikovi, and vice versa. But PfeifTer denies this — and the negative results obtained from the serum reaction with Metchnikoff's spirillum and cholera-immune serum show that the organisms are not identical. The Spirillum op Relapsing Fever (Spirochosta or Spirillum obermeieri*) . — First observed by Ober- meier (1873) in the blood of a patient suffering from febris recurrent. Bacteriologically very little is known of this microorganism. It occurs as long, slender, flexible, motile spirals or wavy filaments, with pointed ends usually from 20 to 30 /< long. Flagella and spores have not been observed. Typically the organisms are found only in the blood and spleen, not in the secretions of patients with relapsing fever, and chiefly at the height of the disease, seldom or never during the intermissions. They stain readily with the ordinary aniline colors, especially with fuehsin and Loeffler's methylene blue solutions; they do not stain by Gram's method. They have never been cultivated in artificial media. When preserved in blood serum and 0.5 per cent, solu- tion of salt, they retain their vitality for a considerable time. Inoculation experiments have been successfully made on man and monkeys. Monkeys when inocu- lated with human blood containing the spirilla take sick after about three and one-half days, but exhibit only the initial febrile attack; no relapse such as is characteristic of the disease in man occurs. Extirpa- tion of the spleen renders the disease more dangerous for these animals. Infection may be transmitted by inoculation also from one monkey to another. Al- though so little is known of this organism from a bacte- riological standpoint, the fact of its constant occurrence in relapsing fever and of the communicability of the disease from man to monkeys by inoculation of the blood gives us grounds for assuming that this is the cause of the affection. Spiroch/ETA Pallida (Treponema pallidum). — This organism is found in large numbers in syphilis or infectious diseases of human beings, characterized by its long course and by the definite stages of its clinical history. It was first observed by Schaudinn working together with Hoffmann, in 1905, in the fresh exudates of chancre, and as it possessed many of the characteris- tics of the spirochetes he named it Spirochata pallida. ♦These organisms are classed with the spirochetes as pro- tozoa by Schaudinn, Hartmann, and others, but by Norris, Novy, and others they are still placed with the bacteria. In this article, therefore, the two most important of the group, only, will be described, viz., Spirochceta obermeieri and Spiro- chmta pallida. Later, because it showed individual characteristics (.having no undulating membrane, though possessing a flageUum), he classed it as a separate genus, Trepo- nema pallidum. Since the investigations of Schau- dinn and Hoffmann, extensive studies on human and experimental syphilis have abundantly corrobor- ated their findings, and this organism IS OOW recogn- ized to be the specific can c of the disease. Microscopical Appearances. — Very delicate in struc- ture. 4 to 20 /! long (average, 10 p) and | to * /« in diameter. It has four to twenty sharp deep spirals. I lagella like anterior and posterior prolongations are often seen. The double flagella occurring rarely at one end are interpreted by Schaudinn aing Longitudinal division, which then takes place very quickly. In the living condition tin' organism is not very refractive and is seen at first with difficulty. Motility. — Its characteristic vements are rota- tion on its long axis which is comparatively rigid, slight forward and backward motion, and bending of the entire body. By the use of the ultramicroscope the motility of the organism is clearly seen. Stamina'. — It stains red by Gram's method, while most- of the oilier spirochetes stain blue. Biological Characters. — Cp to 1909 numerous attempts were made to cultivate this organism in artificial media without success. Schereschewsky, Miihlens, and others, now employ as media (1) collo- dium sacs in tubes of fluid horse serum, (2) horse or human serum heated to 75° C. The spirochetes are not obtained in pure culture, but in what are termed "pure-mixed cultures," as with amebae. Pathogenesis. — So far as known, syphilis in nature appears only in man. Kle.bs in 1879, and since then others, have reported that syphilis could be produced in monkeys by the inoculation of human virus, show- ing many of the lesions characteristic of the disease. Sehaudinn's spirochetes have been demonstrated in practically all lesions of syphilis in man (primary, secondary, and tertiary), including the congenital types, in such numbers and position as to make the majority of workers in this field look upon them as the true cause of the disease. Immunity. — After the development of the primary lesions in syphilis man is usually insusceptible to reinoculation during the active stage of the disease, but during all the stages both man and monkeys can, in some cases, be reinoeulated. Efforts to obtain an attenuated virus to be used for inoculation have been unsuccessful. Fresh material loses its virulence in six hours, and the results of inoculation with such virus have been entirely nega- tive. Passage through monkeys does not attenuate the virus. The injection of large quantities^ of the serum of syphilitics into monkeys has failed to produce definite immunity, although some animals after such treatment did not take syphilis. Wassermann, Neisser, and Bruck, have applied the so-called "Bordet-Gengou phenomenon" as a diag- nostic test for syphilis, usually spoken of as the " Wassermann reaction." This test will be described in detail elsewhere. The Glanders Bacillus (Bacillus mallei). — This bacillus was discovered by Loeffler and Schiitz (1882) in the tissues of animals affected with glanders. It was isolated in pure culture by several bacteri- ologists, almost simultaneously, and was proved to lie The cause of the disease with which it is associated. Microscopical Appearances. — Small bacilli (2-3 a long and 0.4 ft broad) with rounded or slightly pointed ends; they usually occur singly, but sometimes in pairs, and they rarely grow out to long filaments. Involu- tion forms are common in old cultures. (See Plate X., Fig. 4.) Motility. — Non-motile. Spore Formation. — Absent. 873 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Staining ReactioJis. — Stains with difficulty with the ordinary aniline colors; does not stain by Gram's method. The bacilli often exhibit a granular appear- ance (metachromatic bodies) which are especially visible with Neisser's stain. Biological Characters. — Aerobic and facultative anaerobic, growing both with and without oxygen, but best in the presence of oxygen and at brood tem- perature, though it develops slowly at 2.5° C; does not grow at over 40° C. It may be cultivated on all the usual artificial media, but best on five per cent, glycerin agar. On glycerin agar at the end of twenty-four to forty- eight hours it forms whitish, transparent colonies which in six or seven days may attain a diameter of 7 to S mm. On blood serum a moist, opaque, shiny layer of a yellowish or dirty-brown color is developed. The serum is not liquefied. On potato the growth is very characteristic. At the end of twenty-four to thirty-six hours at 37° C, a moist, yellow, transparent coating develops, becoming deeper in color and denser in consistence until it finally presents a reddish- brown color, and the surrounding surface of the potato acquires a greenish-yellow tint. The cultures often exhibit long, felt-like, interlaced filaments not unlike the threads of the bacillus anthracis, and finally club- like enlargements. In bouillon a diffuse clouding takes place, a tenacious, ropy sediment being ulti- mately formed. Milk is coagulated with the produc- tion of acid. Vitality. — The resistance of cultures of the bacillus of glanders is not very great. They lose their viru- lence quickly by natural weakening as early as the fourth or fifth generation; therefore in order to retain virulence it is necessary after two or three generations of cultures to pass the virus through a susceptible animal. According to Bonome the glanders bacillus dies in ten days when exposed to a temperature of 25° C; but other authorities find that it may live for three months under similar conditions. Exposed to heat the bacilli are killed at 80° C. in five minutes, and at 100° C. in three minutes. Corrosive sublimate solution (1 to 1,000) destroys the bacilli in fifteen minutes, and five per cent, car- bolic acid in one hour. The virulence is quickly lost in distilled water (six days); it is not destroyed by putrefaction. Pathogenesis. — Among domestic animals, horses, asses, cats, dogs, goats, sheep are the most susceptible; less so pigs. Cattle and birds are immune. Among test animals, the field mouse, wood mouse, and guinea- pig are the most susceptible, the rabbit being less so, while white mice and house mice are comparatively immune. When pure cultures of the Bacillus mallei are injected into horses and other susceptible animals true glanders is produced. The disease in the horse is characterized by the formation of ulcers upon the nasal mucous membrane. These ulcers have irregu- lar, thickened margins and secrete a thin, virulent mucus; the submaxillary glands become enlarged and form a tumor; other lymphatic glands also become inflamed, and some of them suppurate and open ex- ternally, leaving deep ulcers; the lungs are finally in- volved and the breathing becomes rapid and irregular. In farcy, which is a more chronic form of the disease, circumscribed swellings appear in different parts of the body, especially where the skin is thinnest, which sup- purate and leave angry-looking ulcers with abundant purulent discharge. Pure cultures can be obtained from the interior of the suppurating nodules and glands which have not yet opened to the surface; but the discharge from the nostrils or from an open ulcer contains comparatively few bacilli, and these are asso- ciated with so many other bacteria which grow more readily than the glanders bacilli on culture media that it is difficult to obtain pure cultures in this way by the plate method. Here test animals are useful 874 In guinea-pigs subcutaneous injections are fol- lowed in three or four days by swelling at the point of inoculation, and a tumor with caseous contents soon develops, then ulceration of the skin takes place. The lymphatic glands become inflamed, and in from two to three weeks symptoms of general infection appear. In male animals orchitis and epididymitis are present, while the internal organs (lungs, kidneyB, spleen, and liver) are generally the seat of character- istic nodular formations. From these pure cultures may be obtained. The specific ulcers produced upon the nasal mucous membranes of the horse are rarely present in guinea-pigs. The process is often prolonged, and the animals may live from six to eight weeks after inoculation; or it remains localized in the skin. Intraperitoneal injection of guinea-pigs is usually followed by death in from eight to ten days, and in males the testicles are invariably affected. In female animals the disease may be communicated to the fetus. The bacillus of glanders has never been found out- side of the animal body nor in healthy individuals. The disease occurs as a natural infection only in horses and asses, but it may be communicated to man by contact with affected animals, and usually by inoculation through wounds of the skin or mucous membranes. In man, where the virus enters, a local swelling appears, which spreads rapidly, accompanied by suppuration and cording of the neighboring lymphatics. Multiple abscesses are formed in the skin, muscle, and internal organs, and there are often suppurative changes in the joints, the disease at this stage resembling pyemia. Characteristic glanders nodules a,ppear in the mucous membranes, particu- larly of the nose, which soon disintegrate, forming ulcers. The disease not infrequently terminates fatally, death resulting from general infection carried by means of the lymph circulation. It is transmissible from man to man. Washer- women have been infected from the clothes of a patient. Among horses it is by no means an uncommon disease, particularly in Southern countries, sometimes taking a mild course and remaining latent for a considerable time. Horses apparently healthy, therefore, may possibly spread infection. It is often difficult to demonstrate microscopically the presence of the glanders bacillus in the nodules which have undergone purulent degeneration, or in the discharge from the nostrils, ulcers and glands. Strauss has proposed the following rapid method of diagnosis by inoculation of test animals: Some of the suspected material or culture is introduced into the peritoneal cavity of a male guinea-pig, making the inoculation directly in the middle line of the abdomen, to avoid introduction into the vesiculae seminalis. If it is a case of glanders, the testicles begin to swell within thirty to forty-eight hours, and the skin over them becomes hyperemic, shiny, and finally degener- ates and shows evidences of pus formation. The diagnostic symptom is the tumefaction of the testicles. The diagnosis of glanders in horses, in which the clinical symptoms of the disease may be obscure, as in chronic or subacute cases, may often be made by the use of mallein. Mallein consists of the filtered pro- ducts of the glanders bacillus — albuminous com- pounds bearing a similar relation to glanders that Koch's old tuberculin bears to tuberculosis — pre- pared by evaporating a six-weeks'-old culture in five per cent, glycerin nutrient veal broth to ten per cent, of its original bulk. The dose of mallein is about 1 c.c. subcutaneously injected, which usually gives good reactions. An injection of mallein under the skin of a healthy horse has no effect or at most produces a slight local swelling and rise of temperature. Following an injection of mallein into a glandered horse two reactions are produced: a large and painful swelling at t lie point of inoculation and a rise of tem- perature to 104° or even 106° F. The rise of tempera- REFERENCE II WDI'.ot )|< • )K THE MEDICAL SCIENCES Bacteria ture, however, should not be taken alone as con- clusively iiuliciiting glanders; it must be considered iii connection with the local swelling and the general condition of the animal which is profoundly affected by the injection. The practical value of this test has been demonstrated by numerous experiments by veterinarians. No ill effects have been found to result from the injection of mallein in healthy horses. On the contrary, not only production of immunity, but some cures have been reported from its use. An agglutination test may also be made for glanders by the macroscopic or microscopic method. In the macroscopic method (Mcissner and Schultz) a forty-eight-hour glycerin agar culture of Bacillus mallei is washed off with normal salt solution, to which sufficient carbolic acid has been added to make a 5 per cent, solution. This is incubated for two hours at 60° C, then filtered and enough of the earbolized normal salt solution is added to give the emulsion a slight, milky appearance. The serum is then made up into the required dilution, 1:50, 1:100, etc., and 1 c.c. of each dilution is pipetted into stoppered sterile tubes, an equal amount of the emulsion being added to each tube. The tubes are incubated at 37° C. for twenty-four to forty-eight hours. If a reaction occurs the upper part of the fluid will be clear and a fine granular sediment will be found at the bottom or fine clumps clinging to the sides of the tubes. In the microscopic or hanging-drop method a twenty-four-hour glycerin broth culture which has been heated to 60° C. for one minute, is used and the test is made as in the Widal test for typhoid fever. The cover glass and slides must be sterilized and the hanging drops made carefully and quickly to avoid contamination. The slides are left at room tempera- ture or at 22° C. for eighteen to twenty-four hours and then examined microscopically. In this method the reaction can be observed earlier than in the tubes, and it is not necessary to wait for precipitation which at times takes place slowly. The microscopic method also gives a higher reading than the macro- scopic method and includes more horses which are doubtful. The agglutination is 1:500, but many apparently healthy horses will agglutinate the Bacillus mallei in dilutions as high as 1:5,000 to 1 :10,000. The cause of this is not understood. Such horses then should be subjected to the mallein test from time to time, with a view to the possibility of a slight infection taking place. Very rarely a horse in the last stages of glanders will fail to give a reaction, but the disease symptoms will then be well defined. The agglutination reaction has been found also to be a valuable guide to the use of mallein. In human cases the reaction of 1:100 and above is considered positive, the normal blood not reacting above 1 :50. The Bacillus of Bubonic Plague (Bacillus Testis bubonica?). — This organism was discovered by Kitasato and Yersin, independently, during an epidemic of the bubonic plague at Hong-Kong, China, in 1891. This disease, like anthrax and leprosy, has a long historical record behind it. It is probably the disease which under the names of "Black Death" or "The Great Plague" decimated the population of Europe in the Middle Ages. Microscopical A p pearances. — Short rods, with rounded ends, about twice as long as broad, occurring singly, in pairs, or in short chains (especially in bouillon cultures), and often surrounded by a capsule. Involu- tion forms are common. (See Plate X., Figs. 7 and 8.) Motility. — Non-motile, possessing no flagella ; though Kitasato claims that it has very sluggish, scarcely perceptible movements, and Gordon states by a special method of staining (Van Ermengen's method) he found polar flagella. Spore Formation. — Absent. Staining Reactions. — Stains with the ordinary aniline dyes, but in preparations made from ; cultures the character) tic bipolar staining, which is observed in preparations fr blood and pus, is not readily obtained. Hoes not .-tain by Gram's method, Biological Character Strongly aerobic, growth being inhibited in the all I nee "I oxygen. Develops on i he u uaJ culture media, but be I on bl I erum al 37° C; also fairly well at room temperature. ( >n gelatin plates small, darkly defined granular colonies of a grayish-yellow to greenish color develop; the gelatin i not Liquefied, in gelatin stab cult it grows slowly on the surface and along the track of the needle. On glycerin agar it grows rapidly, form- ing a moist, grayish-white coating on the surface. i in blood ■ i r a in in the incubator, at the end of twenty- four to forty-eight hours, white, moi I tran parent, and iridescent colonies are formed. Bouillon becomes diffusely clouded, but if inoculated with a cohesive mi of bacteria from an agar culture the bacilli develop as a granular or grumous deposit on the walls and bottom of the tube, the upper portion of the liquid remaining clear, similarly to what is observed in the growth of some varieties of streptococci. There is a scanty growth on potato and milk; milk is not coagulated. The Bacillus of bubonic plague forms no gas in media containing sugar, and but little indol. It produces toxins, and the serum of animals immunized against the bacillus yields antitoxic substances. Vitality. — The bacilli of bubonic plague withstand desiccation for from three to seven days: in water they die in from three to eight days according to its composition; in buried cadavera they retain their vitality for twenty-eight to thirty-eight days. Ex- posed to the action of direct, sunlight they are de- stroyed in from three to four hours. They are killed by heating at 55° C. in ten minutes, and at 80° C. in five minutes. Corrosive sublimate (1 to 1,000) de- stroys the bacilli immediately. Pathogenesis. — This bacillus is pathogenic for almost all animals, only pigeons being immune. Guinea-pigs, rats, and mice are the most suceptible animals; somewhat less so are monkeys, rabbits, cats, and horses; and still less so are dogs and cattle. Guinea-pigs when injected intraperitoneally with pure cultures die in about two days of acute septicemia, few bacteria being found in the tissues. At the point of inoculation there will be seen a hemorrhagic infiltration and edema, with enlargements of the mesenteric glands and parenchymatous congestion of the organs. The spleen sometimes shows minute nodules resembling miliary tubercles, which contain zooglea-like masses of the bacilli. Guinea-pigs are also easily infected through the digestive tract. Flies, bedbugs, fleas, and other insects take up the organisms with the blood of plague-infected animals, and the disease is frequently transmitted through them, especially fleas, to man. Hankin and Yersin have repeatedly found non- virulent plague bacilli in the dust of infected houses and in the soil. They have never been found in healthy individuals. Among animals the bubonic plague is known to occur spontaneously in rats, which often are affected previously to human epi- demics. Ground squirrels in California have been shown also to be susceptible to infection and they are supposed to help spread the disease. In patients suffering from plague the bacilli are found chiefly in the pus of the characteristic buboes and also in the sputum from the pneumonic forms of the disease; more rarely in the internal organs and the blood. This organism is the specific cause of true Oriental bubonic plague, the mortality from which is from fifty to eighty per cent, of cases. It gains access to the body (1) through the skin. Here the bacilli may remain localized and multiply at first in the neighboring lymph glands; frequently at the point S75 Bacteria REFERENCE HANDBOOK OF THE MEDICAL SCIENCES of inoculation a pustule is formed which takes on the nature of a furuncle or carbuncle containing many bacilli. Death may occur without further diffusion of the organisms, but ordinarily they are distributed throughout the entire body, producing death by septicemia. (2) Through the lungs. This constitutes the so-called pneumonic form, or plague pneumonia. The bacilli are present in the sputum and sometimes in the blood; other pus cocci are found in association. (3) Through the digestive tract. This mode of infection has been demonstrated in animals, but is uncertain in man. Immunity. — Yersin. Calmette, and Borrel have succeeded in producing passive immunity against the plague bacillus in animals, and also to a certain extent in man, by subcutaneous inoculations with the serum of horses which were previously immunized by intravenous inoculation of dead cultures. Such serum possesses also some curative effect in men and animals suffering from the plague, if inoculated with large quantities and within twelve hours after infec- tion. Roux maintains that this serum contains only antitoxic, not bactericidal, substances. Active immun- ity may also be produced, and apparently without danger, by Haffkine's method of preventive inocula- tion in the same manner as with cholera. This method consists in the subcutaneous injection of 2.5-3 c.c. of a fully grown bouillon culture heated for one hour at 70° C. to kill the organisms. The reac- tion caused (fever and pain) is usually slight, and the injection is best repeated after ten days. This treat- ment is essentially protective rather than curative, and although the immunity afforded is not absolute and lasts only for a month or two, the majority of those inoculated are protected or have the disease only in a mild form and recover. By means of these two methods of inoculation, along with strict quarantine regulation and the destruction of rats and fleas, it is to be hoped that this disease which, under the name of Black Death, once decimated the population of the earth and which in the East still causes a great mortality may be finally exterminated or greatly restricted. The German Plague Commission considered puncture of the unopened bubo for diagnostic purposes some- what dangerous, on account of possible infection of the blood; but the English physicians in India make a long incision in the affected gland, which is afterward dressed with antiseptics. In this way material is obtained for cover-glass specimens, plate and other cultural methods. The pus of the buboes, and es- pecially the sputum in the pneumonic forms, contain numbers of bacilli. In these cases microscopical examination alone suffices often to make a probable diagnosis of the plague from the peculiar bipolar staining of the organisms. Microscopical examination of the blood is attended with success only in cases of general infection, and here cultures yield better results. It is recommended to make streak cultures on gelatin plates at 22° O, at which temperature the plague bacillus grows fairly well, while the streptococcus and other associated bacteria usually exhibit only scanty growth. According to Hankin, wdien the bacilli are grown on agar containing 2.5 to 3.5 per cent, of salt at 31° C, in twenty-four to forty-eight hours inoculation forms, consisting of pear-shaped bodies and spheres. are developed, which he considers characteristic enough to form a means of diagnosis. Finally, the serum of men and animals affected with the plague possesses the power of agglutinating the bacillus pestis. This reaction is said to be present in the second week, and is most pronounced in the second and third weeks of the disease. Arthur R. Guerard. Reff.rentf.s Park and Williams: Pathogenic Bacteria and Protozoa. Sternberg: Text-Book of Bacteriology. Fliigge: Die Kficroorganiamen. Lehmanii utul Neumann: Bacteriologische Diagnostik. 876 Bacteria Carriers. — It has been known for several years that persons convalescent from certain acute infectious diseases may thereafter carry and excrete the exciting organisms from their bodies for a variable length of time. Almost coincidently it was discovered that not only those who have suffered from a specific infectious disease may harbor the causative organisms but also others who have been in direct contact with either such patient or the infectious material. These persons are apparently in normal health, or do not show any symptoms of the specific disease. Recently the general term "bacteria carriers" or "bacilli carriers" has been applied to such persons. It is difficult to define strictly what constitute true bacteria carrier. The term is subject to broad interpretation, but, as commonly understood at the present time, certain restrictions may be made to fix proper limitations. Therefore we may say provi- sionally that a "bacteria carrier" is one who, while apparently in good health, or at least not showing any symptoms of a particular specific infectious disease, is harboring and excreting the infectious agent of such virulence that, when transmitted directly or indirectly to a second person, or to an experimental animal, it is capable of causing the disease in question. The carrier may or may not have given a history of a previous attack of the disease. According to Novy, carriers may be classified under three types— convalescent, chronic, and healthy carriers. But, as he points out, perhaps the so-called healthy carriers in most instances are individuals who have had the dis- ease unknown to themselves at some previous time, therefore they are really "chronic carriers''. In other cases, while apparently healthy, the individual may be in the incubation stage of the disease which de- velopes later. After excluding these possibilities a group remains which may fulfill the required qualifi- cations for a strictly healthy carrier. As evident, the term "healthy carrier" is one which can not be correctly applied in certain cases, so must be used with reservation. The first observations upon carriers were made in connection with epidemics of cholera, diphtheria, and cerebrospinal meningitis. This list of infectious diseases is being constantly added to as investigations continue along this line. Asiatic Cholera. — It has been found by a number of workers in epidemiology that in cholera epidemics there are healthy persons in the infected district who carry virulent vibrios in their intestines, but who are themselves apparently insusceptible to the disease. Abel and Claussen reported an extreme case in which they found cholera vibrios in the dejecta of fourteen out of seventeen persons belonging to families wherein there were cholera patients. In some instances the organisms persisted as long as fourteen days. In the Hamburg epidemic there were reported twenty-eight cases of healthy persons with normal stools containing cholera vibrios. Cholera vibrios are usually found in the dejecta of patients for only a few days, but Kolle found virulent organisms in the stools of convalescents up to forty-eight days. A case has been reported in which the organism was found one hundred and twenty days after the attack. It is evident from the above that the dissemination of cholera comes about not only through contamina- tion of water, food, etc., from the discharges of those acutely ill of the disease, but also from the discharges of certain convalescents and healthy "carriers," who may play an important role in spreading the ili-ease. For efficient quarantine purposes laboratory examinations of the feces, as well as clinical examina- tions, must be directed toward those who have come from infected regions, or have been exposed »ther- wise to the disease. Diphtheria. — As early as 1S94 Park and Beebe ex- amined the throats of three hundred and thirty REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteria Carriers healthy persons. In eight subjects virulent diph- theria bacilli were found, and two of those afterward developed the disease; twenty-four subjects in this aeries showed non-virulent or attenuated forms of the organism. In further studies upon the persistence of the virulent organisms in the throats of convale cent a large series of consecutive cases were examined. It was found that in approximately fifty per cent, of the cases tin' bacilli disappeared within three days after loss of the pseudomembrane. A majority of the remaining patients showed the disappearance of the organisms in rapidly decreasing numbers over the following two weeks. But in a few cases the bacilli persisted from the fourth to the ninth week. Park later reported the ease of a patient who carried fully virulent organisms for eight months. Prip reported a case in which the virulent organisms persisted for twenty-two months. IVnnington has published the results of his ex- amination of the throats of a large number of well school children in Philadelphia. The summary of his findings is very interesting in this connection. He found that approximately ten per cent, of these children harbored in their throats bacilli which cor- responded morphologically with the organism of diphtheria. One-half of these organisms were without effect upon guinea-pigs. About thirty per cent. behaved like attenuated forms, and fourteen per cent, killed the animals with a fair degree of prompt- ness. In the examination of the throats of well persons in contact with diphtheria patients, Kober found that eight per cent, carried virulent bacilli. It is generally considered that the bacilli found in well persons recently exposed are more likely to be virulent than others. .Many more studies along these lines have been made which confirm the findings just mentioned. All these observations point to the fact that not only convalescents but apparently well individuals may serve as carriers of virulent diphtheria bacilli, and under favorable conditions can infect others. Specific antitoxic serum, likewise medicinal treat- ment, apparently exerts little if any influence in correcting this condition in diphtheritic convalescents. Cerebrospinal Meningitis. — The Diplococcus intra- cellularis meningitidis of Weichselbaum is another or- ganism which is found in normal persons. In the examination of twenty-seven healthy persons Schiff found in the nasal secretions of seven an intracellular diplococcus; in three cases of this group Weichsel- baum identified the organisms as being meningococci. Weichselbaum and Ghon isolated the same organism from three persons who had been in contact with the disease. Goodwin and von Scholly found the meningococcus present in about ten per cent, of the people who were in close contact with patients suffer- ing from the disease. Others have found the menin- gococcus in the throat and nasal cavities of healthy persons, during an epidemic of meningitis. The organism may persist a considerable length of time in convalescents. Goodwin found the organism per- sisting sixty-seven days after the onset of the disease. Evidence seems to indicate that cerebrospinal meningitis is not highly contagious. Those who con- tract the disease usually have had their general resis- tance lowered by unhygienic environment, hardships, exposure, etc. Individual susceptibility is an im- portant factor. The organism may set up an acute rhinitis without further invasion or harm. This partly explains how the infection may be carried and distributed, as it is well known that the organism Eossesses a low degree of vitality; it is rapidly killed y drying, sunlight, etc. Therefore, immediate or mediate transmission of the infected secretions from one person to another seems to be necessary in most cases in Dwelling infections arc not proved The fluence oi "bacteria carriers" in the spreading of thi dises aci ounl foi the out bn afa and finement to one family, -mall ana in a community, •«■ ingle regiment. P cerebrospinal meningitis in ba origin from "bacteria carriers." instances arc on record which would indicate that tl Influenza. — The influenza bacillus may be barb in the respiratory and na al pa ages of mat ell ons, « bo seem u o 1 heir act ii • iject 3 who have had the disease may harbor the bacillus for I d ome ei i ca es n I In- frequent, po ably due to an autoreinfection. They maj also 11 ndary infection in many other conditions. Williams quite early observed tnem in sputum from pulmonary tuberculosis; they present in great numbers in a large portion of the • -i es, and in somi almo 1 pure cult u Moreover, they were found not only during the wintx r but also during the summer, when no influenza was known to be prevalent. There is no doubt that tuberculous patients act as influenza bacilli carriers. ■ certain healthy persons play a similar r61e. Typhoid Fever. — Perhaps the most thorough studies upon "bacilli carriers" have been carried out in connection with typhoid. fever. Several exten reports have recently appeared upon this subject. Although these conditions have been recognized only within the last few years, the investigations prom- ise to throw much light upon certain outbreaks of the disease of obscure origin. At the present time considerable work upon this phase of the epidemio- logy of typhoid is being pursued both in this country and abroad. It has been known for a number of j T ears that typhoid patients and convalescents might carry pure cultures of the bacillus in the bladder for an inde- finite period of time. Petruschky in 1898 reported typhoid bacilli in the urine of convalescents, as tongas two months after the attack. Richardson soon after mentioned a case, observed by Cushing, of a man who had had typhoid fever five year-, previously, but returned to the hospital for treatment of cystitis. Bacteriological examination revealed a pure culture of typhoid bacilli, which would indicate that the in- fection had been carried five years, following the typhoid-fever attack. The above observations have been fully confirmed. In certain cases typhoid convalescents carry the bacilli a variable length of time as bladder infections, and thus become a source of infection to others by discharging the organisms in the outer world. Donitz and others have reported cases which fully support the claim that infections can originate from such a source. As early as 1902 Frosch suggested that convales- cents from typhoid fever in some instances might carry the bacilli in their bodies as saprophytes, and their dejecta might give rise to new infections. In this way the mystery of "typhoid houses" or "ty- phoid localities" might be explained. Sound persons might be "bacilli carriers" and be the source of infection. Drigalski and Conradi in the same year reported the isolation of typhoid organisms from the dejecta of four healthy persons who had been in contact with cases of the disease. Drigalski in 1904 reported a case in which the organisms were observed for nine months in the stools. The next year Lentz and others confirmed the supposition of Frosch and the findings of Drigalski and others. Since then many more contributions have been made on the subject winch give further support to the views concerning " typhoid- bacilli carriers." Lentz (1905), in making an extensive review of the 877 Bacteria Carriers REFERENCE HANDBOOK OF THE MEDICAL SCIENCES results obtained at several laboratory stations engaged in the investigation of typhoid fever, stated that out of a large number of examinations ninety-eight chronic "bacilli carriers" were found. At one station it was found that about four per cent, of the cases examined became bacilli carriers. In one instance Lentz found that out of twenty-two carriers sixteen were women. He observed that a definite relationship existed be- tween gallstone disease and "bacilli carriers," as the two conditions might be associated, and suggested that gall-bladder infections might give rise to the typhoid bacilli in the feces. Neiter has called attention to the influence of bacilli carriers in causing institutional epidemics. In a certain German insane asylum were found thir- teen " bacilli carriers, " all women. Friedel traced the cause of a series of typhoid outbreaks in the institu- tion, to a " carrier" who was a helper in the kitchen of the asylum. Kayser reported small outbreaks of typhoid fever which could be traced to the milk in use. In two in- stances the milk was traced back to the respective dairies. In each case a "carrier" was found in connection with the dairy, proof being furnished by the isolation of typhoid bacilli from the feces. Kossel describes a similar outbreak which had its origin from milk supplied from a certain dairy. Upon investiga- tion it was found that -one of the laborers was a "bacilli carrier," although he was not aware that he ever had the disease. He was removed from the dairy work, with the result that no more cases developed from the milk supply. Later, he returned to the work and a second outbreak followed. Besides the German cases cited, similar cases have been reported in this country recently. These examples prove very instructive, as they show the danger of em- ploying "bacilli carriers" as workers about such places. Soper records a most interesting and instructive case of a typhoid-bacilli carrier. He was called upon to investigate a household epidemic of typhoid fever, where, in close succession, six out of eleven were stricken with the disease. The water and food sup- plies were fully examined, with the result that they could be excluded as sources of infection. Finally, suspicion was directed to a cook who had been em- ployed by the family shortly before the outbreak of the disease. She left shortly afterward. Soper succeeded in locating the cook again, but was unable to derive any useful information from her. She was a woman of apparently good health, about forty years of age, of Irish descent, single, and had no knowledge of ever having had typhoid fever. She refused to give further information concerning her past life, and the investigator therefore found it necessary to look up her past history. During the previous ten years it was possible to trace her where- abouts with the exception of two years. It was found that in the time accounted for she had been employed in eight families, and in seven of these typhoid fever had followed her. She had always escaped the epidemics herself. In all, twenty-six cases and one death occurred in the series of outbreaks. The last position she held was with a family in New York City, and the outbreak in this instance was followed by the only fatality. Soper called the attention of the Department of Health to the cook, who was suspected of being a chronic carrier and a menace to public health. She was placed in the Detention Hospital March 19, 1907, where she was kept under constant observation for almost three years. Bacteriological examinations were carried out, under the directions of Dr. Park of the Research Laboratory, by Goodwin and Noble which showed that the urine was free from typhoid bacilli, but the feces were rich with the organisms. Examinations were continued during the period of detention which showed that typhoid 878 bacilli were present in the stools (in varying numbers) off and on at irregular intervals while under observa- tion. The blood showed a positive Widal test early in the course of the examination. This side of the' in- vestigation was not followed along with the feces examination, owing to the vigorous protests of the carrier. It is not necessary to dwell upon this case further than to call attention to the havoc which a carrier can produce when coming in direct contact with the food supply of non-immune individuals. Klingler divides typhoid-bacilli carriers into two groups: (a) those who have had typhoid fever at some time or other, and (6) those who have no knowledge of ever having had the disease. In a series of twenty- three cases which came under his observation, he found that six men and five women fell in the first group, while in the second group there were three men and nine women. The discharge of typhoid bacilli in the feces of carriers may be quite irregular in some cases, while regular in others. This seems to depend on temporary conditions in the intestinal tract. It has been observed that sometimes the discharge of bacilli will suddenly stop without recurrence. Also there may be all degrees of gradation as to the length of time the bacilli continue to be present in the feces after the acute attack. They may not be found at all after convalescence, or they may be present weeks, months, or years thereafter. Lentz mentions one case in which the organisms were present forty-two years after the attack. From this we can easily see that there may be no age limit. Klingler in his series found bacilli carriers between the ages of eighteen months and sixty years. The infant cases may have been contracted through the mother. The focus of infection is generally considered to be in either the gall-bladder, chronic ulcers of the intes- tines, or the normal intestinal tract. Wasserman and Citron are of the opinion that a local immunity exists in the gall-bladder and intestinal wall of the carrier,, which protects the body from general infection. A number of workers report that there is no raising in value of the specific agglutinin, nor in specific .bac- tericidal substances; but others have reported that such substances are increased. It is desirable that more work be done in regard to these particular points. Medicinal treatment or immunization, according to Forster and Kayser, seems so far to have been attended by practically no favorable results, in the intestinal cases. But in the bladder infections Richardson found urotropin very efficacious. The use of this drug might be of service in the gall-bladder infections in some cases. A successful use of urotro- pin in gall-bladder infection was reported from the Johns Hopkins Hospital soon after this type of carrier was recognized. But, beneficial results have not always followed its use. When the infection in these cases can be localized by such evidence as concomitant gall-stone disease, operative means may in some cases lead to cure. Dehler in 1907 operated upon a patient who was a chronic bacilli carrier, with the purpose of relieving the condition. Perhaps this is the first operation on record which was undertaken for the cure of a typhoid carrier. The patient, an insane woman, had infected a number of persons before it was discovered that she was a carrier. Previous to the operation typhoid bacilli were found in the feces in thirty-seven out of thirty-nine examinations. The operation consisted in making a section, freeing the gall-bladder from adhesions, opening it, and removing the gallstones, then giving free drainage for some time. The patient made an uneventful recovery, and with the exception of once shortly after the operation, the stools were reported to be free from typhoid bacilli. Later on Dehler operated upon a second patient REFERENCE HANDBOOK OF THE MEDICAL BCIENCES Bacteria Canieri i-ho was a bacilli carrier, and removed a lew small tones from the gall-bladder. Subsequent examin- tions of the feces showed the absence of typhoid lacilli. In the same communication he reported luil thr dejecta of I he previous case still remained ree from typhoid organisms. Both patients showed hi improvement in their general condition. Dehler 11 ■ It 1 the opinion that operative moans wore justifiable ii those oasos in which no relief from the condition an be brought about by medication or immuniza- ion. Albert in a recent study upon the subject of chronic yphoid-bacilli carriers, stated that probably five per ■cut. of all typhoid patients become chronic carriers. it her writers place the percentage from one to five per int. Albeit also slated t hat ten per cent, of all cases ire traceable to carriers, and called attention lo (lie menace which chronic carriers are to public health. The hitler fact is being more fully recognized by the health authorities now, and attempts are being made for the control of the problem in so far as is i ical. A number of eases have been reported in which the dejecta of chronic carriers have shown a mixed infection of the paratyphoid with the typhoid bacillus. Also paratyphoid bacilli carriers have been .. -ported by Gaehtgensand others. Bacillary Dysentery. — As compared to typhoid fever, a limited amount of work has been done which will throw light upon the subject of bacilli carriers among convalescents from dysentery or of healthy carriers. But, taking up the closer study of certain epidemics of this disease, it seems possible that there are carriers in some instances. However, the investigations of Shiga, Flexner, Goodwin, and others, carried out in a large number of cases, have failed to show the presence of B. dysertteriw in normal Mi.nl- In tivs disease, as in those discussed previously, the so-called latent types apparently may be a means of spreading the infection. Park is of the opinion that paradysentery bacilli are distributed by carriers and may in some cases give rise to epidemics. Duval reported that he had found in two instances the B. parady sentence in the normal stool of milk-fed infants. Collins also found in a few cases the organ- ism in the normal stools of babies. Gonorrhea. — Many of the so-called cases of chronic gonorrhea may be considered in the sense of being gonococci carriers. A certain percentage of the so- called chronic or latent cases do not show any clinical manifestations after a certain length of time following the acute infection. Yet these persons are quite capable of infecting others, and there seems to be no decrease in the virulence of the organism. Moreover, the person is subject to superinfection from other sources with acute clinical symptoms following. Apparently there is no limit to the time a man may carry the infection in chronic cases. Park mentions a ease in which the organisms were abundantly present after an exposure dating back twenty years. Another class of carriers may be those who have experienced slight if any clinical symptoms primarily, but who carry the organisms and are able to infect others. Malta Fever. — Convalescents from malta fever in some cases may carry, and excrete from the bladder the Micrococcus melitensis for a considerable time after an attack of the disease. Bruce quoting the work of Kennedy states that theorganism is excreted with the urine in ten per cent, of the cases. This is continued in some instances as long as two years after the patient is convalescent. Shaw also made similar observations. The organism has been found in the gall bladder of man (Horrochs and Kennedy). Since the urine not infrequently shows the organism for considerable time after the patient's convales- cence, it is not improbable these carriers may be a i: " toi in i he I"- ad of tin- disease; i he organ! m tains its vitau'l j and \ irulem , • for some I ime. Plague— H is que tionable ii pe I bai illi can in i In- en i- that we i on ider t\ phoid bai illi < for example, are to be recognized. In the bul type ol the 'ii ea e, com ale cent i nl Inue to eliminate virulent organisms from the affected gk for a .-,.,, iderable time after i he otl ptom have abated. But such a condition could hard] included under our definition of bacilli carriei ( In 1 be oi her hand, the pneu nic type of the disea e may in some rare in tance afford examples which simulate true bacilli carrier Got i hlicn reported i hree except lonal ca e b hicb can oder hi obs vation during the Uexandria pesl epidemic in 1899. These cases were of the pneumonic type, and each made a recovery; two were complicated with bul while the third showed no bubo. The sputa from these cases showed virulent pi- t bacilli fort v-ee twenty and thirty-three days after complete di ap- pearance of the fever. As evident, the one case in particular without bubo, (3rd) might easily bave escaped detection, without tl»- bacteriological exami- nations, been discharged, and readily spread the infec- tion. Padlensky states that in an epidemic of plague of the pneumonic type, the specific organism maj be found On the tonsils of well people, 1 1ms in- dicating that heal l hy carriers may l bus exist. Bacilli isolated from such carriers, wen- slightly virulent for guinea-pigs, but after an animal passage I lie vi nil- increased, lie called attention to the importance of carriers in pest epidemics, and the need of further in- vestigations. ( )l her observers have noted the presence of pest bacilli in the sputum for some time after con- valescence of the patient. While probably very rare, the possibility still exists that in plague, among the recovered, certain eases may be considered bacilli carriers for a short time. Other Infectious Diseases. — Pncumococci and strep- tococci are quite frequently found in the throats and air passages of normal persons. While these organ- isms are nearly as virulent to susceptible animals as when obtained from diseased eases, we are not yet certain whether they are as capable of producing disease in man. Many cases of pneumonia are undoubtedly due to autoinfection. Concerning the tubercle bacillus we need further investigation. There may be certain persons who may harbor the bacilli and still give no evidence of any pathological condition caused by this organism. But this supposition seems to be improbable. As concerns the group of diseases caused by filtrable virus little as yet has been done in relation to the human carrier. The work of Osgood and Lucas upon poliomyelitis, showed that in monkeys the virus remained viable and infectious in the naso- pharyngeal mucosa several months after the acute paralytic stage of the disease. But the central nervous system did not retain the virus, for the same length of time, in a virulent condition. It is possible that a parallel state may exist in the human con- valescent from this disease, and may act as a source of infection to others under certain conditions. Bacteria carriers, or bacilli carriers, as stated, are a constant, menace to public health when allowed unrestricted freedom. It is imperative that such cases bo recognized if possible, and the necessary steps taken, so far as is feasible, to combat the con- dition, or to prevent the spread of the disease by prophylactic means. Patients recovering from these diseases should be thoroughly examined before being discharged in order to a certain whether or not they are free from virulent organisms. It is essential that more than one examination should be made of fecal discharges from suspected typhoid or cholera carriers, when the lirst examination has given negative results. As the 879 Bacteria Carriers REFERENCE HANDBOOK OF THE MEDICAL SCIENCES organisms do not appear constantly in the dejecta in many of these cases, it is evident that a single examination will not always reveal the true condition. Medicinal treatment, immunization, or surgical intervention may relieve certain cases, but when these means are not applicable it may be necessary to quarantine the patient. In all cases in which the dejecta carry infectious organisms complete steriliza- tion should be employed. In safeguarding a water supply these bacilli carriers must always be kept in view. When investigating the origin of an outbreak of an infectious disease, it is always important to bear in mind the possibility of a bacteria carrier as the source. L. W. Fa.uulener. Bacteriacese. — A family of Schizomyeetes, or fis- sion-fungi, comprising cylindrical, more or less elon- gated, straight (never spiral) forms, with or without flagella, with or without endospores, dividing only in one, the transverse, plane. It includes three genera: 1. Bacterium, without flagella: 2. Bacillus, with peri- trichal flagella: 3. Pseudomonas, with polar flagella. Bacteriological Technique. — The methods for the artificial cultivation of bacteria are of fundamental importance in bacteriology, and for that reason de- serve very careful consideration. Nutrient media of various kinds are used, but the three most commonly employed are bouillon, gelatin, and agar. These in turn may be variously modified as the needs of the work may require. In addition, other media are used, such as blood, serum, exudates, eggs, urine, milk, potatoes, and the like. These will be severally considered. Bouillon. — To prepare beef tea, or bouillon as it is called, 500 grams of lean, chopped beef (Hamburger steak) are placed in a suitable enamelled vessel or in a one-and-a-half-liter flask and 1,000 c.c. of ordinary tap water are added, and the whole is thoroughly mixed. This may now be set aside in an ice-box for twenty-four hours so as to bring the soluble constitu- ents into solution; or, what is preferable, it may be placed in a water-bath and warmed at a temperature not exceeding 60° C. for an hour. In this way the nutrient substances are dissolved out and much time is saved. It is not desirable at this point to heat the fluid above the temperature given, inasmuch as that would lead to the coagulation of the albuminous, constituents, which, if they are allowed to remain in solution, will facilitate the subsequent clarification of the medium. When the digestion is completed, whether carried out at a low temperature or in the water-bath, the liquid is strained through well- washed, starch-free muslin, or the juice may be expressed by means of a meat press. The liquid thus obtained is of a dark red appearance, due to the presence of hemoglobin. One thousand cubic centimeters of the meat extract are then placed in a clean flask or vessel, and ten grams of dry, powdered peptone ( Witte's) and five grams of common salt are added and the whole is then warmed at about 55° to 60° C. till the peptone has dissolved. The next step is to render the medium suitably alka- line, since bacteria as a rule require a slightly alkaline soil. This manipulation requires special care, for, if improperly done, the finished product may be cloudy, or may have a deposit, or may even be unfit for the growth of bacteria. The clouding and the formation of a precipitate can be avoided by boiling the meat extract after adding just enough alkali to neutralize the fluid. For this purpose 5 c.c. of normal sodium hydrate (four per cent, solution) are added to the liter of meat extract. This amount is usually sufficient to make the extract neutral to litmus. The liquid is then heated in a boiling water- 880 bath or over a free flame for about fifteen minutes after which it is filtered through a moist plaited filter and allowed to cool to about 50° C. As stated bacteria thrive best when the medium is slightly alkaline. Hence 10 c.c. of the normal sodium hydrate are now added to impart the desired alkalinity, after which the liquid is again boiled for twenty to thirty minutes, and finally filtered through moist paper. Inasmuch as considerable water is usually lost by vaporization during the preparation of the medium it is advisable either to indicate the volume at the beginning of the operation by a suitable mark on the vessel, or, better, to take the weight of the fluid before and after heating. The difference in the volume or weight is finally made up by the addition of the corre- sponding amount of distilled water. The finished bouillon should make up to the original volume of meat extract, that is, 1,000 c.c. The beef tea thus prepared is now filled into tubes or into flasks, as the case may be, and sterilized by steam. This process will be described later. It is hardly necessary to add that the bouillon after being tubed and sterilized should be perfectly clear, without a deposit, and should have a slight alkaline reaction. For cultivating the gonococcus Thalmann recom- mends using the ordinary bouillon, to which has been added two-thirds to three-fourths of the amount of alkali necessary to make it neutral to phenolphthalein. Bouillon may be prepared by substituting meat ex- tract in place of the meat infusion. The preparation of the meat extract bouillon will be considered later. Sugar-free Bouillon. — The bouillon as just prepared always contains some sugar derived from the muscle tissue employed. For many purposes this sugar con- tent is undesirable, and must be removed in some way. One procedure is to allow the meat extract to ferment at a low temperature, 10° to 15° C, for two days. Another is to place the meat extract at 37° C. for twenty-four hours. Neither one of these methods will give results which can be relied upon. The best procedure is to add to the meat extract a rich fluid culture of some acid-producing organism, such as Bacillus coli (Smith), or B. lactis aerogenes (Dunham), and then set it aside to ferment at 37° C. for twenty- four hours or longer. The frothy liquid is then carefully neutralized by the addition of normal sodium hydrate, peptone and salt added, then boiled, cooled, and rendered alkaline according to the directions given under the preparation of bouillon. The sugar-free bouillon thus prepared does not con- tain indol, as might at first be supposed. It is pref- erable to the Dunham peptone solution mentioned below for testing for the presence of indol, since a good reaction is given in sixteen hours, whereas the cultures in Dunham's solution often require several days before giving a positive test. Martin's Bouillon. — The thoroughly mixed meat suspension (500 grams of chopped beef and 1,000 c.c. of water) is set aside at about 37° C. for twenty hours so as to destroy the sugar normally present. The liquid is then strained through well-washed muslin, and to 1,000 c.c. of the filtrate five grams of common salt are added, after which the liquid is neutralized and finally rendered alkaline by the addition of 7 c.c. of normal alkali per liter of bouillon. Ordinary peptone is not added, inasmuch as it is likely to con- tain sugar. Instead, Martin adds to this bouillon an equal volume of a rich peptone solution made by digest- ing the stomach of a pig. This latter solution is pre- pared as follows: A pig's stomach is cleaned and cut up into small pieces, and to 200 grams of this finely divided tissue 1,000 c.c. of water and 10 c.c. of con- centrated hydrochloric acid are added and the mix- ture is set aside at 50° C. for about twelve hours. The digested fluid is then decanted through a filter of absorbent cotton and the strongly acid reaction is reduced by the addition of 25 c.c. of a sixteen per cent, solution of sodium hydrate. The liquid is then RKIT.KI'.XCK HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique carefully neutralized, after which ii is rendered alka- line by the addition of 7 c.c. of normal sodium hydrate per liter. The mixture of equal volumes of (lie sugar- free bouillon and the peptone solution is heated, filtered, and tubed or placed in flasks. Peckliam's Bouillon. — This is made by taking finely chopped beef, which must be as old as it can be obtained in order that it may be free from muscle sugar, ami adding 225 grams of it to 500 c.c. of water. The mixture is rendered slightly alkaline with sodium Carbonate, after which it is placed in a water-bath at 40° C, and four grains of trypsin are added. After digesting for an hour the fluid is again rendered alka- line with sodium carbonate. In from one to oik 1 and a half hours the digestion should be arrested, other- wise traces of indol may be detected. At the end of this period the mixture is boiled and strained through gauze and filtered cold through wet filter paper to remove the fat. Five grams of salt and enough water to make up to one liter are then added. The acidity of the clear straw-colored filtrate is then reduced to the desired point. The most suitable reaction for tin' development of colon and like bacilli is when the medium contains such an amount of free acid as to require from 20 to 30 c.c. per liter of a decinormal sodium-hydrate solution to bring it to a point neutral to phenolphthalein. Artificial digestion of muscle tissue by means of pepsin and trypsin is resorted to in the preparation of Deycke's agar. Dunham's Peptone Solution. — This is prepared by dissolving ten grams of Witte's peptone and five grams of common salt in 1,000 c.c. of ordinary tap water. The solution is then tubed and sterilized by steam. This medium is used to detect the formation of indol by bacteria, but inasmuch as many organisms fail to grow in it and others require several days before giving a reaction, it has not been found to be as Suitable as the sugar-free bouillon given above. Glucose Bouillon. — This is used to test for acid and gas production. It is made by adding to the ordinary bouillon, or better to that which is sugar-free, one or two per cent, of glucose. The two per cent. solution is most commonly employed. The steriliza- tion of sugar-containing media by steam requires special care to prevent oxidation of the carbohydrate present. As a rule the steaming should not exceed ten or fifteen minutes each day on three successive days. Instead of glucose other carbohydrates, such as lactose, maltose, saccharose, dextrin, etc., may be added to the bouillon in one or two per cent, con- centration. Mannite-peptone Bouillon. — The alcohol mannite is added to sugar-free bouillon in sufficient quantity to give a one per cent, concentration. This medium is especially useful in differentiating organisms which otherwi. e closely resemble each other. For example, the different varieties of dysentery bacilli may be separated, since certain ones ferment mannite, while others do not. Glycerin Bouillon. — This is especially used for cultivating the tubercle bacillus. It is made by adding five per cent, of glycerin to the ordinary bouillon. The mixture is then tubed and sterilized in the usual way. Carbolic Bouillon. — This is made so as to contain 0.1 per cent, of carbolic acid. One gram of acid may be added to one liter of bouillon. The better pro- cedure is to add 1 c.c. of a one per cent, carbolic acid to 9 c.c. of bouillon. It is advisable to incubate the tubes for several days so as to eliminate any possible contamination. The medium is useful for examining water for the colon bacillus, especially when the bacterial contents are very high. The presence of the antiseptic serves to check or prevent the growth of many organisms which would otherwise develop. It should be borne in mind that weak colon and typhoid bacilli are likewise restrained. Vol. I. — 56 i he tubes after inoculation with the water are Incu- bated for twentj -four lenu al 3g i ■ , ft ft< r which lai tose litmus agar plate in m uie, which are I i camined for red colonies, < if com ,• all red colonies are not to be regarded without further stu.lv OS the colon bacillus. Parietti's Bouillon. — A mixture of carbolic acid and hydrochloric acid is first prepared l>v adding i c c. of the latter to 100 r.v. of a li pel cent, carbolic solul ion. I hi i olution after s tanding a fe added in portions of o.l, 0.2, 0.3 c.c. to portioi 10 c.e. each of Sterile bouillon. Nitrate Bouillon. — The Laboratory Committee of the American Public Health \ ociation recommi that this medium be prepared by dissolving one gram peptone in one liter of tap water 1 amnion ia-ftv I , and then add two grams of nitrite-free potassium nitrate. Ten cubic ceiiti lei's of I he dium are placed in test-tubes and sterilized in the usual manner. It is be I to prepare the medium fresh before using. Calcium-salt Bouillon. Bolduan found that the addition of certain calcium salts to plain broth gave a medium nearly equivalent to time containing serum or ascitic fluid for the cultivation of the pneu- mococcus, lueningococcu .etc. It has I he advantage of being easily and rapidly prepared. Calcium chloride can be used in solution of I to 2,000 in plain broth, while calcium carbonate (marble) or calcium sulphate (gypsum) is broken into small pier. ., washed with water, added to broth in test-tubes, and sterilized in the regular manner. Pneumococci as a rule grow readily upon this medium, live approxi- mately as long as upon ascitic broth, and retain their virulence equally well. Hiss, working inde- pendently of Bolduan, discovered the same advan- tages of calcium broth when cultivating the above- mentioned organisms, his publication appearing later. MacConkey's Bile-salt Media. — Bile salts and various sugars enter into these media. A stock solution may be prepared without sugar, then the sugar may be added as desired. This solution is pre- pared by dissolving twenty grams Witte's peptone in 1.000 c.c. distilled water heated to 00° C, then to this are added five grams sodium taurocholate (com- mercial product). For the medium one-half per cent, of a freshly prepared one-per-cent. solution of neutral red and the sugar are added. If glucose is used, one- half per cent, is added; in the case of other sugars, one per cent. The medium is sterilized in a steam sterilizer at 100° C. on three consecutive days. Care must be exercised in order not to overheat and split the constituents in sterilizing. Instead of using distilled water as a solvent for the ingredients, beef broth may be used, thus giving a bile salt bouillon. These media are especially applicable in the differ- entiation of intestinal bacteria. The formation of both acid and gas may be observed if the organisms under cultivation possess such proper! ies. Colored Bouillon. — Various coloring agents are added to the nutritive media in order to bring out the acid-producing or the reducing properties of bacteria. The substances which are most commonly used for this purpose are litmus, neutral red, fuchsin, saffranin, and sodium indigo sulphate. The first two are particularly useful, and are prepared the same as the corresponding agar or gelatin media, which see. Gelatin. — The ordinary nutrient gelatin is really nothing more than bouillon to which ten per cent, of gelatin has been added so as to impart solidity with the additional advantage that the medium is trans- parent. The method of preparation is as follows: To 1,000 c.c. of the meat extract, prepared according to the directions given under bouillon, 100 grams of the best sheet gelatin are added; likewise ten grams of Witte's peptone and five grams of common salt. The whole is then warmed in a water-bath at 00° C. 881 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES until the gelatin has passed into solution. The liquid is then neutralized and enough alkali added in excess so as to impart a suitable alkalinity. As ordinarily prepared the nutrient gelatin requires from 30 to 35 e.c. of normal alkali to effect neutralization. An additional 10 c.c. will give the desired alkalinity. Hence 40 c.c. of the normal alkali may be added at once and the liquid tested with litmus paper. If the liquid is not distinctly alkaline more of the reagent may be added until the desired alkalinity is obtained. The method of standardizing media by means of phenolphthalein will be given later. When the proper amount of alkali has been added to the gelatin solution the latter is placed in a water-bath, the water of which is then raised to the boiling temperature. The gelatin is kept immersed in the actively boiling water for about three-quarters of an hour. Prolonged heating or sterilization at high temperature (autoclave) lowers the solidifying point of gelatin; therefore this must be avoided, since it impairs the medium. The albuminous con- stituents of the meat extract coagulate in flakes, and at the same time clarify the liquid so that on subsequent filtration the gelatin will be perfectly clear. In case the coagulation of the albumin results in minute particles, which cannot be readily removed by filtration through paper, egg-albumin may be added and precipitated by again heating. This is brought about by allowing the medium to cool down to 60° C. and to each liter add the whites of two eggs, then thoroughly mix by stirring. Gradually bring the temperature up near the boiling-point, without stirring, and keep there about fifteen minutes. A heavy coagulum results, the greater part of which will rise to the surface. This may be removed by straining through several thicknesses of cheese cloth or a layer of absorbent cotton placed in a funnel. The gelatin is then filtered through a plaited filter, which should, however, be first warmed by passing through it several hundred cubic centimeters of boiling water. If the paper and funnel are sufficiently warmed in this way there is no likelihood of the gela- tin solidifying on the filter. The filtered gelatin should be perfectly clear, should possess a slight alka- line reaction, and should solidify when cooled under running tap water. If it meets these requirements it is then filled into sterile tubes to a depth of one and a half to two inches, and finally the tubes are sterilized by steaming for a quarter of an hour on each of three consecutive days. Whenever nutrient gelatin is mentioned in bac- teriological work it is understood to be a ten per cent, solution. This medium melts at about 23° C. That is warm summer temperature, and for that reason it is sometimes advisable to add more gelatin to the preparation in order to make it more solid. A twelve or even a fifteen per cent, solution of gelatin is used under these conditions. Again, at other times it is desirable to employ a gelatin which is relatively quite soft, and in that case a five or eight per cent, solution may be made use of. Obviously the amount of alkali necessary to neutralize such media will vary from that required for the ordinary gelatin. The great value of the gelatin medium lies in the fact that it can be readily melted and again solidified, and in its transparency. Moreover, many bacteria give rise to soluble ferments or enzymes which pep- tonize or liquefy the gelatin, whereas others are not able to do this. It becomes possible therefore to divide bacteria into two large groups, according as to whether they liquefy or do not liquefy gelatin. Glucose Gelatin. — This is made by adding to the clear filtered gelatin, prepared as above, two per cent of glucose. The material is then tubed and sterilized the ~ame as ordinary gelatin. This medium is par- ticularly useful for the cultivation of anaerobic bacteria. Glucose Litmus Gelatin. — To the glucose gelatin a concentrated solution of litmus is added so as to impart to the medium a deep blue color. This is then tubed and sterilized. During the steaming of this medium the litmus is usually decolorized, but on subsequent cooling the blue color returns. If such a medium is overheated in the process of sterilization the sugar will be altered, and as a result the color of the litmus will change to more or less of a red. For special purposes other sugars may be added to the gelatin, as in the case of bouillon. A lactose litmus gelatin is very useful in differentiating various organ- isms. The amount added is usually one or two percent. Eisner's Medium. — The addition of gelatin to a potato extract, instead of to a meat infusion, was first resorted to by Holz. Eisner's medium is essentially Holz's potato gelatin, to which one per cent, of potas- sium iodide is added. It can be used to good advan- tage in differentiating between the typhoid and the colon bacillus, but at the same time it should be re- membered that it does not afford an absolute means of detecting the former organism. The method of preparation is as follows: 1,000 grams of well-cleaned potatoes are cut up into lumps which are then mashed as fine as possible, best done by passing the material through a fruit press. The fineh 7 mashed potatoes are then placed in a meat press and pressure is applied. In this way about -400 c.c. of a dark liquid is obtained from the kilogram of potatoes. The potato juice is then set aside in an ice chest overnight, after which it is filtered through cotton. Ten per cent, of gelatin and one per cent, of potassium iodide are then added to the dark liquid, and the mixture is warmed at about 40° C. until the gelatin melts. Inasmuch as the reaction of this material varies considerably it is necessary now to determine the exact degree of acidity present, and then to reduce this by the addition of the proper amount of alkali, so that the resulting medium has an acidity such that it would require the addition of 20 c.c. of normal alkali per liter to make the solution neutral. The acidity of the gelatin is determined by titrating a portion, say 10 c.c, with decinormal sodium hydrate, using litmus paper as an indicator. If, for example, 10 c.c. require 3.2 c.c. of the decinormal alkali, it will be necessary to reduce the acidity by adding 1.2 c.c. of decinormal alkali, or better 0.12 c.c. of normal alkali for every 10 c.c. of gelatin made. When the proper degree of acidity has been imparted to the medium, the gelatin is placed in a boiling water-bath for three-quarters of an hour until all the proteins have coagulated, after which it is filtered through peper, filled into sterile tubes, and sterilized by steaming for fifteen minutes on each of three consecutive days. Fish Gelatin. — Five hundred grams of chopped fish are added to 1,000 c.c. of water, and the material is digested the same as given above for ordinary gelatin. To the strained liquid 100 grams of gelatin, forty grains of salt, five grams of glycerin, and five grams of aspara- gin are added, and the mixture when perfectly fluid is rendered slightly alkaline. It is then heated, tubed, and sterilized as above. This medium is particularly useful for the growth of phosphorescing bacteria. Nutrient Agar. — One drawback to the ordinary gelatin is that it cannot be used as a solid medium at temperatures above 23° C. This has led to the introduction of agar-agar as a stiffening agent. This substance is a seaweed gathered off the coast of Asia. It has no nutritive qualities of its own nor is it lique- fied by bacterial ferments. Therefore it becomes a very useful addition to media for special purposes. The preparation of nutrient agar is very simple. Ordinary bouillon is first made according to the direc- tions already given. The agar may be obtained as a powder or in threads; in the latter case the agar is cut up into very small pieces, and twenty grams itwo per cent.) is then added to the liter of bouillon, which should be in a large flask, or, bettor, in an enamelled jar. The vessel and contents should then be weighed, 882 REFEREXCF. HANDBOOK OF Nil: Minn \I. 51 II II ii ti ri..i.iuii il Technique after which the liquid should be gently boiled until the agar has completely dissolved. The vessel is now again weighed, and the difference I i the two weights is made up by the addition of the proper amount of distilled water. It is advisable to place the agar now in a water- bath at about 50° C. for several hours in ordi allow the sediment to settle as much as possible. The filtration of a two per cent, agar is a very slow and tedious process even when carried out in a steam sterilizer. It is sufficient for practically all purposes to tiller through a layer of cot- ton. The filtrate thusobti is almost, if not entirely, clear; ordinarily whatever little sedi- ment may be present .Iocs n ,,i interfere with the usefulness of the medium. If much sedi- ment is present in the filtrate, it may be clarified by the ad- dition of egg-albumin as men- tioned under the preparation of gelatin. The filter is prepared by plac- ing a piece of ordinary cotton, about two inches square, in the angle of a large funnel, and then while it is held down by means of a glass rod, a liter Fig. 543. — Filtration Through Cotton Or SO of Very hot Over a Porcelain Plate. (Novy.) water is passed through, once or twice, so as thoroughly to warm the funnel. Event- ually the sedimented agar is carefully and slowly decanted on to the cotton filter. If desirable the agar can be filtered a second time. A very con- venient arrangement for the rapid filtration of agar through cotton is shown in Fig. 543. This consists essentially of a Witte's perforated porcelain plate, which is steadied in place in the funnel by means of a glass rod which passes through the center. The plate is covered with a layer of cotton on which a similar porcelain plate is placed to prevent the cotton from floating. The funnel is inserted into a strong vacuum flask, which is connected with a Chapman air pump. Boiling water is first passed through the filter to warm it thoroughly, after which the agar is added and suction applied. As soon as the pump begins to act the top plate can be removed. When it is desired to make a perfectly clear medium it should be made with only one or one and a half per cent, of agar instead of two per cent., as given above. Such agar is softer and can be passed through a previously moistened filter paper, especially if the funnel is placed in a steam sterilizer or in a funnel- shaped copper water-bath, such as is shown in Figs. 544 and 545. The filtered agar is then tubed and sterilized by steaming one-half hour on each of three consecutive days, after which it is kept in an upright position; or sterilization may be rapidly accomplished by plai ing the tubes in an autoclave (Fig. 559) and keeping at a temperature of 120° C. for fifteen minutes. Agar media modified by addition of sugars (or certain chemicals) cannot be sterilized at this high tempera- ture since those constituents are altered. When it is desired to make inclined or slant agar tubes, as many of these as are needed are melted in a water-bath and then inclined so that the agar comes within an inch of the cotton plug. Thtdmann's Agar. — Five hundred grams of meat are boiled for one-quarter of an hour with 1,000 c.c. of distilled water, after which the mass is made up to the original weight and strained through muslin. One per cent, of peptone and 0.5 per cent, of salt are then added and the liquid is boiled, after which it is again made up to the original weight, cooled, filtered. < ine and one-hall i then added and the weighed liquid i In a concen- trated salt-water bath for about three-quart hour, after which it is again made up to the original weight. Thirty cubic ei are then titl with normal sodium hydrate, using phenolphtha as an indicator. The amount of alkali necessary to neutralize the entire a unl of agar is ascertained, and two-thirds of this quantity fa then added, in portions and while shaking, to the agar. After heat- tug fifteen minutes the material i- filled into tu According to Thalmann and others this medium is adapted for the cultivation of the gono eially for diagnostic purposes. A httli ms is d with the water of condensation, and then by s of a wire, rod, or cotton swab the suspension is thoroughly spread over the surface of a series of inclined tubes or over Petri di-hes. The-,, when kept for twenty-four hours at 36 37 I mall, glistening colonies, which are single or confluent and : like highly refract i\ 6 dl The medium is not suitable for subcultures, and Thalmann recommends thai the colonies be trans- planted to serum bouillon. This is prepared by adding to some bouillon two-thirds to three-fourth's of the amount of alkali needed to neutralize the liquid. After heating and filtering, an equal volume ot serum is added and the mixture tubed. The tubes are inclined and heated for one to two hours at 70° C. on the first and also on tin' second day. and for one hour at 100° Con the third day. According to Wa mann hog serum is just as good as human serum for cultivating the gonococcus. Glucose Agar. — This is made by adding to the filtered agar, or to so much of it as may be wanted, two per cent, of glucose. The medium is then tubed and sterilized by -teaming for twenty or thirty min- utes on three consecutive days. It is used especially for the growth of yeasts and anaerobic bacteria. If desired, it may be colored with litmus as in the case of gelatin. Lactose, maltose, saccharose, or other sugars may be used as a modification, instead of glucose. The medium in either case is made in the same manner, with similar percentages of sugar. i'n. 544. — Double-Walled Hot-Water Funnel. 1 io. 545.— Single-Wall Hot-Water Funnel with Ring Burner. Rnthhrrgcr's Xcutral-red Agar. — This can be made by adding to a 0.3-per-cent. glucose agar one per cent, of a saturated aqueous neutral-red solution. The typhoid bacillus does not change the color or produce gas, whereas the colon discharges the red and leaves a fluorescing color. The inoculation can be made either by planting a shake culture or by making a stab culture, which can then be covered with a layer of agar to exclude air changes. The addition of neutral red to bouillon is of service in water examinations (Irons. Jordan). SS3 Bacteriolostical Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Endo's Fuchsin Agar. — When properly prepared, this medium ranks among the first as a reliable means of differentiating the Bacillus typhosus. It is prepared as follows: To 1,000 c.c. neutral three per cent, agar (made in the regular way) add ten grams chemically pure milk sugar (lactose); 5 c.c. alcoholic solution of fuchsin (freshly filtered); 25 c.c. ten per cent, solution sodium sulphite; 10 c.c. ten per cent, solution of soda. The milk-sugar solution and fuchsin solution are added first to the dissolved agar and well mixed. The solution of sodium sul- phite is added gradually until the color of the medium disappears. On solidifying, the medium should re- main colorless. Put in tubes (about 15 c.c. each) and sterilize in steamer for thirty minutes on three consecutive days. Keep tubes in the dark until ready for use. Endo ascribes the resulting color changes to the fact that fuchsin is a hydrochloric-acid combination of rosanilin. Rosanilin is a colorless leucobase, but, in combination with acids, gives colored compounds. The sodium sulphite used in the medium is just sufficient to reduce to the colorless base, thus giving a practically clear medium. In the presence of sugar of milk such organisms as B. coli liberate lactic acid, which in turn acts upon the Leucobase, and gives a deep red combination. But the colonies of B. typhosus developing in this medium do not produce an acid, therefore they have a clear glassy appearance, or slightly bluish in transmitted light. Plates are made and inoculated in the ordi- nary manner from infective material. Incubation is canied out at 37° C. and, when suspected colonies develop, they may be fished out, transplanted, and given the agglutination test with specific serum to identify positively. The Malachite-green Enriching Method of Lent:. — This method has also been used extensively in the separation of the typhoid bacillus, especially in the cultivation from feces. The use of malachite green for this purpose was first introduced by Loelfier. Lentz and Tietz have modified and improved the method. They direct that three pounds of chopped lean beef be macerated in two liters of water for six- teen hours. Express the extract, cook for one-half hour and filter, add three per cent, agar to the filtrate and cook slowly for three hours to dissolve. Then add one per cent, peptone, 0.5 per cent, sodium chlo- ride, and one per cent, nutrose (may be omitted). Make neutral to litmus with soda solution, boil, and filter into small flasks of 100 c.c. to 200 c.c. capacity. Before adding the malachite-green solution, test with neutral litmus paper, and slowly alkalinize with sterile soda solution until the litmus strips give a distinct red violet. The crystals of malachite green (Hoechst) should be used to make this solution. Lentz used different concentrations of the dye in preparation of the medium, but Simon recommends a concentration of 1:22,000 as being the most favor- able. In such case make a fresh solution of 1:22(1, and of this add 1 c.c. to each 100 c.c. of the hot agar, thus obtaining the required concentration. The me- dium is poured in Petri dishes, and allowed to cool for use. Inoculations may be made upon its surface. The dye inhibits the growth of B. coli and many other organisms but in the above concentration the B. typhosus develops slowly, usually from two to four days. When kept in the incubator at 37° C. typhoid colonies give the agar a yellow color. Test by specific agglutinating serum to identify. Results obtained by different observers have varied. It seems to be difficult to secure a uniform preparation of malachite green. Lactose Litmus Agar. — This medium was intro- duced by Wurtz, and is very useful in differentiating between typhoid and colon bacilli. Acid formation in the case of the latter is indicated by a change in the reaction of the litmus. If this medium is made by the addition of two per cent, of lactose and litmus to the ordinary agar it will be found that even typhoid bacilli will give a slight acid reaction. This, however, is not due to the fermentation of the lactose, but to the small amounts of muscle sugar derived from the meat. It is therefore desirable that the agar for this purpose should be made out of sugar-free bouillon, which can be prepared accord- ing to the directions already given. Prolonged boil- ing of the agar must be avoided, inasmuch as the agar itself, since it is a complex carbohydrate, may split off some sugar. It is often preferable to make the plain lactose agar and to add to the tubed and sterilized medium, whenever needed, by means of a sterile pipette, a sterile litmus solution. Obviously other indicators, such as rosolic acid, neutral red, etc., may be added in the same way. Glycerin Agar. — To the ordinary nutrient agar pre- pared as above, five per cent, of glycerin is added. The addition of glycerin serves to keep the surface of the medium moist, and at the same time imparts nutritive qualities to the agar. This medium is very valuable for the growth of diphtheria, glanders, pneumonia, and tubercle bacilli. Glycerin Potato Agar. — In the culturing of the glanders bacillus this medium has been found to be especially valuable. It may be prepared as follows: well-selected potatoes are peeled, washed in clean water, then finely grated on a bread-grater; 500 grains of the potato gratings are added to 1.000 c.c. tap water, and allowed to macerate about eighteen hours in the ice box; then heat to the boiling-point for fifteen minutes; strain through several layers of cheese cloth, or better a layer of absorbent cotton; to the measured fluid add two per cent, of Witte's peptone, and one-half per cent, of sodium chloride, dissolve by heating; one and one-half per cent of agar is now added and dissolved by heating in the autoclave for one hour; the mixture is made neutral, using phenol- phthalein as an indicator; when cool, add the whites of two eggs, mix thoroughly, heat in Arnold sterilizer for forty-five minutes; five per cent, of glycerin is added to the filtered solution, then the medium is tubed and sterilized in the autoclave for thirty minutes. Mannite Agar. — Mannite, which like glycerin is a polyatomic alcohol, was first used by Norris and Hiss as a means of differentiating the typhoid from the dysentery bacillus. The latter organism (Shiga type) does not give rise to acid production when grown on mannite media, whereas the typhoid bacillus does. The agar should be prepared from sugar-free bouillon, and to it one or two per cent, of mannite is then added. Litmus may be added to the bulk medium before it is tubed, or the sterile litmus solution may be added to the sterile tubed agar by means of a pipette whenever needed. Pfeiffer's Blood Agar. — This is made by spreading over the surface of ordinary inclined agar a few drops of human blood. On. the surface thus prepared one is able to cultivate the influenza bacillus. The blood from the lower animals can be used in like manner to good advantage. The human blood required for this and similar pur- poses can be drawn without difficulty by means of a sterile syringe from the large median vein just below the flexure of the elbow. The superficial circulation should first be impeded by means of a rubber tube tied about the middle of the arm. The surface of the skin over the vein to be punctured is thoroughly cleaned by means of a disinfecting solution, such as mercuric chloride or lysol. The needle of the sterile syringe is then introduced into the vein, and as the piston is slowly withdrawn the syringe fills with blood. Five or ten cubic centimeters of blood can thus be obtained in a few minutes. When the needle is withdrawn a compress of cotton, soaked in mercuric chloride, should be applied to the wound. The blood 884 REFERENCE HANDBOOK OF THE MEDICAL S( II \< 1 - Hi. i .-i iiii.it: l<:i! Tecbnlqne must be al unci' transferred either to the surface oi inclined agar or to previously melted agar, cooled t" ,50° C. In the lal ter case it is mixed at once, and I lie tube is then set aside in an inclined position to solidify. Thalhimer's Blood Agar. — This medium is a simple modification of former methods for the preparation of blood near. It is prepared as follows: fre hly drawn beef blood is collected in a suitable jar, contain- ing a number of medium-sized marbles, and defibrin- ated by thoroughly shaking. To the defibrinated blood an equal volume of distilled water is added and laking is brought about. The laked blood is passed through a sterile Reichel filter to remove bacteria. Of the clear, red filtrate 20 to 30 c.c. are added to a liter of sterile, melted agar at 45° C. The resulting medium is clear, and bright red in color. The in- fluenza bacillus grows readily upon this medium. Also, the pneumococcus, streptococcus, and the gonococcus grow luxuriantly. This medium is not applicable to the study of the hemolytic properties of an organism. Blood-agar Mixture. — As mentioned above, human blood may be mixed with melted agar, cooled to 5(1° C, after which the mixture may be allowed to solidify in an inclined position. For diagnostic purposes this procedure has been utilized to detect the presence in the blood of typhoid bacilli, gonococci, and other organisms. Instead, however, of allowing the blood mixture to solidify in the tube it is poured out into a sterile Petri dish, and in this way a blood-agar plate is obtained, on which eventually colonies of the sus- pected organism may develop. The presence of a very few organisms can thus be detected in 1 or 2 c.c. of blood, which would not be possible by direct examination or by staining. The amount of blood which is added to the agar may be varied according to circumstances. Thus it may be one to four, one to two, or even one to one. Blood from the lower animals can be drawn under strictly aseptic conditions into sterile Nuttall's blood pipettes, or into the modified form of Novy, shown in Fig. 546. This can be easily made from test-tubes of various sizes, according to the kind of animal to be bled. Thus a five- eight lis by five-inch test-tube may be used for bleeding a mouse or rat, while a one by eight- inch tube would be used in the case of a rab- bit. The bottom of the test-tube and the end of a piece of glass tubing are softened in the flame of a blast lamp and then brought to- gether. A narrow blast flame is then directed against the test tube about an inch from the bottom. On slow rotation in a horizontal position a thickened constriction results, and as soon as this is sufficiently thick the two ends are drawn apart slowly. A tapering capillary results, which is then sealed in the flame at a point about two inches from the tube proper. The tube is then plugged with cotton and sterilized by dry heat. When it is desired to prepare sterile defibrinated blood a drawn-out tube or a narrow glass rod is passed through the center of the plug. By moving this about, after the blood has been received in the pipette, complete defibrination can be obtained, and that without any contamination from the outside. In the case of the larger animals the blood is best drawn from the carotid artery. For this purpose the animal is anesthetized and the artery exposed for about an inch. After the first incision it is advisable to avoid the use of cutting instruments, and instead to separate the tissues with the fingers. Pressure forceps is then applied at the distal end of the artery. Another pair is then applied about an inch below this point. A finger is then placed under the clamped portion of the artery and a very slight opening is Fio. 546. — Blood Pipette, Novy Form made into the bl l-ve • I. 'I be blades of a very narrow-pointed pair of forceps are then Introduced into the opening, and, when distended, the tip of the sterile blood pipette can readily be ced. Be- fore i his is done, hou-e\ i T , thi tip ehed with a file, then broken off, and the ope,, end sh< be il: id for a moment to u round off I lie -harp edge. \ oon B I he pipi tte is in position the lower clamp is removed, when the blood rapidly rises in the tube. If defibrinated bl 1 i desired, the blood should be stirred by an a \\ he,, serum is wanted, this si irring is' omitti d. oi m as blood ceases to flow . i he pipe! te i- rem.. and the tip is sealed in the bias! lamp. Obviously in the case of small animal the mouse or rat, this procedure is nol applicable. The blood may be drawn up into a syringe from the art A much better way, however, i- to take the blood directly from the heart into a small pipette oi the same form as that used for the larger animals. For this purpose the thorax is opened, the heart is f from the pericardium and rai ed by mean of oval- tipped forceps. The tip of the pipette i- thi duced into the right ventricle. Suction may be applied to the other end of t he pipette in order to obtain the fullest possible yield. I'l 1 can be drawn from very large animals, such as the horse, by introducing a linear into the jugular vein. This is the procedure which is followed in the preparation of antitoxins. The trocar is connected by means of a short rubber tube with a glass tube, which is inserted into the receiving cylinder. In this way several liters of blood can be drawn from the horse at each bleeding. In ordinary laboratory work the blood which lias been collected in the glass pipettes is then transferred to melted agar, which has been previously cooled in the water-bath to 50° C. The amount of blood which is added to each tube will vary with the purpose in view. It may be one part of defibrinated blood to ten of agar or one to five, one to two, or one to one, as the case may be. Exceptionally mixtures of two to one and three to one are used. The blood is then mixed with the agar and the tubes are set aside to solidify in an inclined position. The transfer of the blood to the tubes is best accomplished by means of a sterile drawn-out bulb pipette, such as is shown in Fig. 578, e. The blood agar thus prepared requires no further sterilization, for if the operation has been properly carried out no organisms will be present. The tubes can be used for culture purposes at once, or the}' may be kept for several days to allow any organisms which might be present to develop. This blood medium is invaluable for the cultivation of various pathogenic organisms. On such media it has been possible, for example, to grow for the first time pathogenic protozoa — Trypanosoma lewisi of rats and Trypano- soma brucei the cause of nagana or the tsetse-fly disease (Novy and McNeal). In studying the hemo- lyzing properties of bacteria, it is more satisfactory to prepare blood-agar plates. Usually one part of sterile, defibrinated or cit rated blood is added to nine parts of sterile agar at 45°-50 o C, well mixed, then poured into Petri dishes to harden. The cit rated blood is prepared by bleeding directly into a sterile solution of sodium citrate of such concentration that the resulting blood mixture will contain one per cent. of the salt — this prevents coagulal ion. The organisms under investigation may either be mixed with the blood agar while at a temperature of l~>° C. before plates are poured, or may be streaked over the sur- face of the medium after hardening has taken place in the dish. Nory and McNi al's Blood Agar for Trypanisomes. — Novy and McNeal have succeeded in cultivating a number of the Trypanosoma!:! [Tr. lewisi, Tr. brucei, Tr. evansi, and others) upon a specially prepared SS5 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES artificial medium. It is made as follows: 125 grams of rabbit or beef meat are extracted in 1,000 c.c. of distilled water; add two per cent, of Witte's peptone, one-half per rent, of salt, and two per cent, of agar. Then make alkaline by adding 10 c.c. of normal sodium carbonate. The agar thus prepared is tubed and sterilized in an autoclave at 110° C. for thirty minutes. When cooled to about 50° C, two volumes of defi- brinated rabbit's blood are added and the mixture is allowed to solidify in an inclined position. After the agar has solidified, the water of condensation which settles at the bottom of the tube is inoculated with a drop of freshly drawn blood from the infected animal. The above investigators found that even the first generation thrives upon this medium, and transfers grow luxuriantly. Dieudohne's Blood-agar Medium. — This selective medium has proved to be of high value in the isola- tion of the cholera vibrio from intestinal discharges. Owing to its alkalinity it exerts an inhibiting influence on the growth of fecal bacteria other than the spirilla group. It is usually prepared as follows: 30 c.c. of defibrinated ox blood are added to 30 c.c. of "NaOH solution, thoroughly mixed, then heated forty-five minutes at 100° C. in the steam sterilizer. While still hot mix with 140 c.c. hot nutrient agar, and pour thick plates. The nutrient agar is prepared in the ordinary way, excepting it contains three per cent, of agar, and 'must be neutral to litmus. After pouring the plates they are partially dried by first leaving the dishes open at room temperature for twenty minutes, then placing them in an oven for twenty to thirty minutes at 50°-60° C; finally, the partially covered plates are placed in an incubator at 37° C. over night. This treatment is necessary before the cholera vibrio will grow upon the medium. Several modifications of the medium have been reported. It has been found that the meat infusion may be omitted from the nutrient agar with the advantage that the reaction need not be corrected (Pergola). Pilon found that by using a twelve per cent, solution of sodium carbonate (crystals) instead of the sodium hydrate the plates could be prepared for immediate use without the heating of the blood mixture. Krumwiede found that whole egg might be sub- stituted for the ox blood, and recommends the follow- ing formula, which includes the modifications men- tioned above, for a medium: equal parts of water anil whole egg are thoroughly mixed, then add a like volume of 12-13.5 per cent, sodium carbonate solu- tion, shake mixture, then filter through a thin layer of cotton: steam twenty minutes in the Arnold ster- ilizer. Thirty parts or this product are added to seventy parts of boiling hot agar, well mixed, then medium thick plates are poured. The agar is meat free, and is composed of peptone and salt as commonly prepared, and three per cent, of the agar. The plates are dried at room temperature for twenty to thirty minutes, then surface inoculations may be made at once. This modification offers several advantages; it is a translucent medium which may be quickly pre- pared for use, and gives distinctive colonies of the vibrios. Serum Agar. — This is made by adding variable amounts of sterile serum to the melted agar, which has been cooled to 50° C. in the water-bath. The serum can be obtained by collecting the blood, as given above, in sterile pipettes. The blood is allowed to clot, and eventually when the serum has separated it can l>e drawn up into sterile bulb pipettes and transferred to the melted agar. The largest yield of serum is obtained by using t lie Latapie pipette shown in Fig. 547. This consists of an inner tube, which is freely perforated and the narrow outer end of which is drawn out into a capillary for insertion into the blood-vessel. This tube is held in position within the outer one by means of a rubber stopper. The outer receiving tube, which is about an inch in diam- eter, is provided with two side tubes, one of which is drawn out and sealed while the other is plugged with cotton. The entire pipette is first sterilized by steaming in an autoclave. The tip of the inner tube is then broken, flamed, and inserted into the carotid artery of a rabbit or other animal. The blood should not fill the pipette beyond the inner tube. The tip is then sealed and the pipet te is allowed to remain in a vertical position until the blood has firmly clotted. It is then inverted and the serum, as it is squeezed out of the clot, falls to the bottom. The purpose of the perforated inner tube is to allow more com- plete shrinking of the clot. The serum drains away at once from the clot, and is therefore perfectly clear. When it is desired to re- move the serum the tip of the side tube is scratched with a file, then broken off, and the end is flamed to insure absence of bacteria. The tube is then inserted into a sterile test-tube or flask and by blowing into the other side tube the serum is forced out. It can then be dis- tributed to the agar tubes by means of a sterile bulb pipette. These are ^_^^ then allowed to solidify " * '■ in an inclined position. As in the case of blood agar the medium prepared in this way is perfectly sterile if the manipulation is properly carried out. Inasmuch as sterilization by heat is avoided, the protein constituents of the serum remain in as near to the native condition as possible. Such serum agar makes an excellent medium f or Fio. 547 —Blood Pipetto the pneumococcus and for other Latapie. organisms. Obviously, serum-agar plates can be prepared, if it is so desired, in which case the melted and cooled agar is inoculated with the organism to be cultivated, after which the serum is added and mixed with the agar, which is then poured out into sterile Petri dishes. Serum agar, made by adding human blood serum to melted agar, has been used for the cultivation of the gonococcus (Wertheimer). Ascitic or pleuritic fluid may also be added to agar in the proportion of one part of the fluid to two parts of the agar. Such agar is used especially for the cultivation of the gonococcus. The ascitic, pleuritic, or hydrocele fluids may be sterilized by fractional sterilization or by filtration through a Berkefeld filter underpressure. Wassermann's Serum-nutrose Agar. — This also has been found useful for cultivating the gonococcus. Five cubic centimeters of hog serum are added to 30 to 35 c.c. of water, 2-3 c.c. of glycerin, and 0.8-0.9 grams of nutrosc. Nutrose is a sodium-phosphate casein compound, and when added to serum prevents coagulation on boiling. The solution is boiled for twenty minutes, after which it is added in equal parts to two per cent, peptone agar in test-tubes. This mixture is then poured into Petri dishes. Nu- trose has been used also in the preparation of the Drigalski-Conradi agar. Hog serum, which is said to be as good as human serum for cultivating the gonococcus, has been employed also by Thalmann. Drigalski-Conradi Agar.— This is a meat-peptona nutrose agar containing lactose, litmus, and crysta violet. The preparation is as follows: 1. A mixturi of three pounds of meat and two liters of water is SS6 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriology :.i Ti-cimiquo allowed h> stand for twenty-four hours; the expressed meal juice is then boiled for one hour and altered, To (lie filtrate arc added JO grams of \\ itte's pep- tone, 20 grains of nutrose, lit grams of -odium Chloride, and the whole is boiled for One hour and fil- tered. To this filtrate sixty grams of agar are added and the liquid is boiled for three hours, or < hour in an autoclave. It is then rendered alkaline to litmus paper, boiled half an hour, and filtered. L\ A sol ut ion of litmus is prepared according to Kubel-Tiemann as follows: The powdered commercial litmus is repeatedly ex- tracted with hot distilled water. The liquid is acidu- lated with dilute acetic acid and evaporated to syrupy consistence on a water-bath. The thick fluid is then diluted by the gradual addition of ninety- per-eent . ali ill ml, transferred to a flask, and an excess of ninety-per-eent. alcohol is added. Tins precipi- tates I lie blue pigment, while the red dye and I lie potassium acetate remain in solution. The precipi- tate is filtered and washed with alcohol, then dis- solved in distilled water, after which the solution is wanned and filtered. The filtrate is then added gradually to very dilute sulphuric acid (one or two drops of acid to 200 c.c. of water) till the color changes to a wine red. The concentrated blue is then added till the blue color is restored; 200 c.c. of this litmus .solution is boiled for ten minutes, then thirty grams of pure lactose are added, and the boiling is continued for fifteen minutes. 3. The hot litmus is added to the hot agar, mixed, and the reaction is made slight ly alkaline; 4 c.c. of a hot sterile solution of ten-per-cent. anhydrous soda and 20 c.c. of a freshly prepared solution of 0.1 gram of crystal violet in 100 c.c. of warm sterile water are then added, after which the material is filled into tubes or flasks. Excessive heating should be avoided, inasmuch as it alters the lactose. The crystal violet is intended to restrict the development of the unimportant bacteria. The Drigalski-C'onradi medium has been recom- mended for the isolation of the typhoid bacillus. For this purpose the feces should be diluted with ten to twenty volumes of salt solution. The authors employ large plates, fifteen to twenty centimeters in diameter. The agar is poured into the dishes to a depth of at least two millimeters and the cover is then kept off till the moisture has dried from the surface of the agar. By means of a five-millimeter glass rod, bent at right angles and previously dipped in the suspension, a series of streaks are made over a number of the dishes. The inoculated plates are then kept at 37° C. for twenty-four hours. The colon colonies are large, opaque, and red, while the typhoid are small, glassy, and resemble dewdrops. The further identification of the suspected colony is made by applying the agglutination test and by growing in Rothberger's neutral red agar. MucConkey's Bile-salt Agar. — This medium is pre- pared by dissolving one and one-half or two per cent, of agar in bile-salt bouillon stock solution (see bile-salt medium). If necessary it is cleared with egg-albumin. Neutral red and a given sugar are then added, as in the case of the broth preparation. It is used in the examination of feces, sewage, etc., for intestinal bacteria. The method of procedure is practically the same as that given under the Drigalski and Conradi medium. The growth of most bacteria is inhibited, while that of B. coli and B. typhosus is not. Colonies of acid-producing bacteria appear rose-red in color. Alkali gives a yellow-red with this indicator on plates. Other modifications are used by water analysts. Esculin Bile-salt Agar. — This medium is recom- mended by Harrison and van der Leek in water analysis for the detection of B. coli and certain other excretal organisms. For its preparation they give the following method: 15 grams of agar, 2.5 grams of commercial bile salt, and 10 grams peptone (Witte) are dissolved by boiling in 1,000 c.c. distilled water. The solution I neutralized with normal solution of sodium In. Irate. After cooling dl below tin 1 ( '. t lie v. hite ,,f i wo e L ' L -- ai i -It i Mi ii i i heated |,i boiling to coagulate I he albumin; i he coagulum i- removed by filtration. If i it is neutralized again, and to the hoi filtrate are added 1 gram esculin (Merck) and I gram iron citrate scales (Merck). After solution of tl substances the a< idity is taken with decinormal oda solution, if the acidity proves high, alkali is added to bring down to , 0.6, if too low. more iron citral added until I he react ion is t 0.6. Sterilize by steaming twenty to thirty minutes on three consecutive d [f the direct it 1 1 efully followed in the prepara- tion of this medium it is claimed that ati factory and even results will be obtained. The reaction with a. and some other organisms is due to the splitting of the esculin into glucose and e culetin; the esculetin unites with the iron in the medium to form a dark- brown salt. The medium must be sugar-free in order to give the reaction. Ik lactis aerogenes gives the nin lion but if may be included in "pre uinptive tests" as an excretal organism. Some moulds and laet,.-e fermenting yeasts also gives the test, a fact which must be considered in certain examinations. /;. re// coii uiies in this medium appear black with a black halo about them. While />'. typhosus grows well upon this medium, it does not produce the color reaction. Matzuschita's Liver-gall Agar. — This medium is especially recommended for the cultivation of the intestinal flora. It is prepared a follows: Take 500 grains of finely chopped ox-liver; 30 grams peameal; add 1 liter of distilled water and cook until the soluble constituents are extracted. The residue is removed by straining through muslin, and to the filtrate add 7 grams peptone, 5 grams sodium chloride, and 0.2 gram hydrochloric acid. The whole is carefully shaken and then allowed to stand at 37° C. for three hours. After this 600 grams of ox-gall are added, and the whole is again allowed to stand for three hours at incubator temperature. It is then heated for some time, filtered, and sufficient agar (two per cent.) is added to give solid medium. Filter, place in tubes, and sterilize. This medium, notwithstanding the addition of the hydrochloric acid, remains slightly alkaline. Matzuschita recom- mends, for the culture of intestinal bacteria, that the medium be neutral or very slightly acid. Placenta Glycerin Agar. — Duval and WeUman found that a medium containing untreated placental juice was valuable for the cultivation of B. I from the tissues. Of the different media employed for this purpose, this was the simplest, and one most easily prepared. Its special value seems to be due to the large amount of amino-acids present in pla- cental tissue. According to these authors, the medium is prepared by taking a fresh human placenta and washing out the contained blood by running sterile saline solution through the blood-vessels; after this the placenta is ground up in a meat chopper, To each pound of the chopped up tissue, 0.5 liter of sterile salt solution is added; the mixture is placed in an ice bos and allowed to stand for forty-eight hours; the fluid portion is separated and passed through a pre- viously tested No. N. Berkefeld filter for sterilization; to the clear, amber-colored filtrate, a two-per-cent. sterile agar is added at a lemperat i ire of about 11 ( '.; the addition of t hree-per-cent. glycerin to the agar before sterilization is recommended; the ingredients are thoroughly mixed, placed in tubes and slanted to cool. Placental fluid alone also serves as a good medium for the leprosy organism. It is claimed that transplants of macerated leprosy tissue containing the ai id-last organism will show a visible growth in five to seven days upon this medium. /»'. tubi - culosis and other acid-fast organisms (rat leprosy) grow readily on the placenta medium. a, latin Agar. — Several formulas have been pro- ssr Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES posed for the preparation of this medium. Each rinds its special application. That of C'apaldi was recommended for the isolation of the typhoid bacillus from feces. It is made by dissolving twenty grams of Witte's peptone, ten grams of gelatin, ten grams of glucose or of mannite, five grams of sodium chloride, and five grams of potassium chloride in 1,000 c.c. of water. The solution is filtered and two per cent, of agar is added and dissolved by boiling, after which it is rendered alkaline by the addition of 10 c.c. of normal alkali. The filtered solution is then tubed and sterilized by steaming. Bccr-wort Agar. — Wort is of particular value in the cultivation of yeasts and it is also used in the study of certain bacteria. It may be used in the fluid form, or solidified by means of either gelatin or agar. Eyre recommends its preparation by taking 250 grams of crushed malt and placing it in a two-liter flask with 1,000 c.c. distilled water. The mixture is first heated up to 70° C. in the stoppered flask, then placed in a constant-temperature water-bath, and allowed to macerate at 60° C. for one hour. The fluid portion is separated by straining through muslin; then it is heated for thirty minutes in a steam steril- izer and followed by filtration. The natural reaction of the resulting wort is left unchanged. In case the solid preparation is desired, add two per cent, agar and proceed the same as in the prepara- tion of nutrient agar. Sterilization is carried out by placing in a steam sterilizer at 100° C. for twenty minutes on each of three consecutive days. Stoddart's medium is a gelatin agar which con- tains five per cent, of gelatin, one per cent, of peptone, and a half per cent, each of agar and of salt. A liter of meat extract is prepared in the usual way. In this ten grams of peptone and five grams of salt are dis- solved, and the solution is then divided into two parts. To one portion ten per cent, of gelatin is added, and when this has dissolved, the solution is neutralized and an excess of 10 c.c. of normal alkali per liter is added. The other half of the meat extract is likewise neu- tralized, and then 10 c.c. of the normal alkali are added per liter to impart the requisite reaction. The liquid is then measured or weighed, boiled, and filtered. Five grams of cut agar are added to the bouillon, which is then boiled until the agar dissolves. Dis- tilled water is added to make up to the original volume or weight, after which the two liquids are combined and allowed to sediment. The entire product is finally filtered through cotton or, better, through paper. The medium is filled into tubes which are then steamed for fifteen minutes on each of three consecutive days. To use this medium, it is poured out into sterile Petri dishes, and when solidified the center is touched with the organism to be tested. The typhoid bacillus, on account of its motility, spreads rapidly over the surface as an almost transparent growth whereas that of the colon bacillus spreads less and is easily visible. Guarnieri's gelatin agar is made in a somewhat similar manner. Three grams of powdered agar are emulsified with 50 c.c. of distilled water, and this is then added to a solution of fifty grams of gelatin in 750 c.c. of meat extract. The whole is boiled till the agar has dissolved, when a solution of twenty-five grams of Witte's peptone and five grams of salt is added. The entire liquid, which now makes up to one liter, is then carefully neutralized with normal alkali, using litmus as an indicator. The medium is tubed and sterilized as usual. It has been used to advantage in the culti- vation of the pneumococcus. Weil's Meat-potato Agar. — The potato juice is pre- pared as in the method of Holz or Eisner; 300 c.c. of this are added to 200 c.c. of slightly alkaline bouillon; 3.75 grams of agar is then dissolved in the liquid, thus yielding a 0.75-per-eent. agar solution. The typhoid "bacillus presents threaded colonies on this medium, the same as in Eisner, Hiss, and Piorkowski media. Noguchi's Ascitic-fluid Tissue Agar. — Noguchi has succeeded in making direct cultures of Treponema (Spirochete) pallidum, and other spirochetes from fresh infectious material from man. For this pur- pose a medium is prepared as follows: two parts of two per cent, slightly alkaline agar (at 50° C), are added to one part of ascitic (or hydrocele) fluid, thoroughly mixed in a tube in the bottom of which is a fragment of sterile tissue. Rabbit kidney or testicle is preferable, although other tissues as human pla- centa, sheep-testicle, etc., may be used. The culture medium is allowed to solidify in the tubes, then a layer (three centimeters) of sterile paraffin oil is added to prevent evaporation, and exclude the. air. The material (tissue) for inocidat ion containing the organ isms should be immersed immediately after removal in sterile phy- siological salt solution, containing one per cent, of so- dium citrate, and cut into small bits, some of which are rubbed up into an emulsion in the citrate solution. Each tube is inoculated with some of the bits of tissue by pushing them to the bottom of the culture tubes with a heavy platinum loop, also some of the emul- sified material is deeply inoculated into the same tube by means of a capillary pipette. Care must be taken not to break up the medium. The contami- nating bacteria which are present in first inocula- tions appear to grow along the line of the stab, while the spirochetes grow out into the medium for a distance. The culture may finally be purified by taking transplants from the distant outgrowths and carrying over to fresh medium several times. Noguchi has found this method applicable to the isolation and cultivation of other spirochetal. He succeeded in separating Spirochicta refringens from infected tissue, and growing it in pure culture by the procedure just outlined. Likewise, he isolated in pure culture certain mouth spirochetal (Treponema microdentium, Tr. macrodentium). In these cases, it was necessary to enrich the material by growing one or more generations in a special fluid medium. This medium was composed of a large quantity of sheep serum water (1 part serum and 3 parts of distilled water) in a tube containing sterile tissue (kidney or testicle of rabbit or sheep), and covered with a layer of sterile paraffin oil. The inoculated tubes were incubated at 37° C. for about ten days, during which time the medium became more or less coagulated by the contained bacterial growth. A small amount of the impure culture was removed from the bottom of the tube by means of a capillary pipette, and inocu- lated into a solid medium composed of sterile serum agar (in ratio of 1 to 3) and containing sterile tissue (sheep or rabbit). The procedure was quite the same as mentioned for the inoculation of tubes for the cultivation of Treponema pallidum. After inocula- tion the medium was covered with a layer of sterile paraffin oil to exclude the atmospheric oxygen. Noguchi's Method for Cultivating Treponema Palli- dum in Fluid Media. — Experience has demonstrated that Treponema pallidum cannot be cultivated con- stantly in fluid media (even when they contain fresh, sterile tissue), by the ordinary anaerobic methods. Noguchi has overcome this difficulty by a method in which both solid and fluid media are used in combina- tion for simultaneous cultivation of the organism. The method is as follows: A culture tube is first pre- pared by fusing a short piece of strong glass tubing (0.7 cm. bore) to the perforated bottom of a test-tube 1.7 cm. wide and 20 em. long, thus giving an outlet; after thoroughly cleaning, the larger end of the tube is plugged with non-absorbent cotton, the smaller end (fused in tube) is passed through a perforated rubber Stopper (No. 5), which in turn is fitted into a test-tube 2.5 cm. wide and 15 cm. long. The double tube, as now set up, is sterilized in the autoclave in the regular manner. When cool, the rubber stopper together with the smaller (upper) tube is removed, one or two pieces of sterile, fresh rabbit kidney are placed in the larger 888 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique (lower) till"', then the two pails arc tightly fitted together and not again taken apart. A piece of the tissue, of such size that it will not pass I he bottom outlet, is placed in the upper tube. .Next the Lower tube is tilled from above through the upper tube with ascitic fluid or a mixture of ascitic fluid and bouillon, by means of a sterile hull) pipette. ] hi pipette must have a small outlet tuhe which will easily pass through the connecting tube of the double culture tube, for delivery of the fluid, and freely per- mit the escape of air. The lower tube must be com- pletely filled to exclude till air bubbles. The next step IS the inoculation with 77. pallidum, which should be taken from a well-growing, pure culture. A portion may be aspirated into a long capillary glass pipette (sterile) by means of a syringe connected with a piece of rubber tubing — a part of the material is dis- charged into the fluid in the lower tube, the rest sur- rounding the tissue in the upper tube. After the inoculation the upper tube is almost filled with a solid medium compound of one part of ascitic fluid and two parts of a sterile, slightly alkaline, two per cent, agar, mixed at a temperature of about 42° C. and poured on while still fluid. Finally the surface is covered with sufficient sterile paraffin oil to give a depth of about three centimeters over the solidified agar. The culture is incubated at 37° C. Utmost care must be taken to prevent bacterial contamination during the above manipulations. Noguchi's Method for Cultivating the Spirochetal of Relapsing Fevers. — Noguchi succeeded in growing in pure cultures, four different species of spirochaetffi (.s'/>. duttoni, Sp. kochi, Sp. obermeieri, Sp. novyi) which give rise to the diseases classed as relapsing fever. For this purpose he employed a fluid medium with sterile fresh tissue, and proceeded as follows: a piece of sterile fresh tissue (usually rabbit kidney) was placed in each of a number of sterile test tubes, two by twenty centimeters, to which were added a few drops of citrated blood, drawn aseptically from the heart of an infected mouse or rat; at once about 15 c.c. of sterile ascitic or hydrocele fluid were added to each tube; to some of the prepared tubes a layer of sterile paraffin oil was added others were left without the oil. The presence of some oxygen seems necessary for the growth of the organisms. The blood for inocu- lation of tubes is best when taken from the animal between forty-eight and seventy-two hours after it has been artificially infected. It is essential that ascitic fluids, which are to be used in this medium, must contain no bile, but have the power to form a loose fibrin when added to the fresh tissue in the tube. The maximum growth at 37° C. in the inoculated tubes was reached after seven to nine days. Substitutes for the Meat Infusion. — In the prepara- tion of the foregoing media a meat infusion serves as the basis in each case. In special instances, but not as a routine procedure, these media may be modified by using the commercial Liebig's beef extract in place of the meat infusion. The chief advantage lies in the fact that the beef extract can be kept always on hand. At the same time it must be remembered that media made up with such extract are by no means as nutri- tious as those made up with the meat infusion. The amount of Liebig's extract which is used varies with different workers. In general, from one to three grams are added to one liter of water; five and even ten grams may be used. To this solution peptone and salt may be added in the usual amounts. The liquid when ren- dered alkaline and filtered constitutes a Liebig's- extract bouillon. In the same way gelatin and agar media are prepared. Peptone Substitutes. — Several compounds have been suggested as substitutes for Witte's peptone. In Mar- tin's and Pcckham's bouillon and in Deyeke's agar this peptone is replaced by that which is formed by the digestion of the muscle tissue. In other media derivatives of albumin or casein are employed. Heyden's "Nahrstoff " i ed egg albuminate, while nui rose i a casein compound I he addition of lecil hin, |n gen, he globin, etc., i made with the object ot improving the nutritive qualitii tofthe media. Hiss' Tube Medium. — This is u ed a a meai g for the typhoid bacillus. It i made by add- ing 5 grams of Liebig's extract 5 grams of salt and S grams of agar to 1,000 c.c. ol water. I he mi is then heated until the agar ha di olved, after which the water which i, [ s( by evaporation is replaced and then eight per cent. 'gelatin i added. As soon as the gelatin has di olved, the liquid is partially neutralized by the addition of normal alkali. The reaction is left acid, and to such an e ti ni that ii would require 15 c c. of normal alkali per liter to make the solution neutral to phenolphthalein. The licpiid is then cooled to 60° (', and cleared by the addition of the white of an egg stirred up in about 25 c.c. of water. The liquid is then boiled for a few minutes, after which ten grams of glucose are added. After sedimentation at 50 C. the medium can be filtered through paper or cotton and tubed. This medium is used only for slab cultures. Diffusion of the growth through the medium in the case of very motile organisms, such as the typhoid bacillus, anil the production or absence of gas, are the criteria sought lor. Hiss' Plate Medium. — Hiss utilized the tendency of the typhoid bacillus to form threaded colonies when grown on soft media, as a means of differentiation from the colon bacillus. The medium, as first pro- posed, contained 1.5 grams of agar, 15 grams of gelatin, 5 grams each of Liebig's extract and of sodium chloride, 10 grams of dextrose, and 1,000 c.c. of distilled water. This was cleared by the addition of the whites of two eggs and filtered through absor- bent cotton. The reaction was left acid, and of such extent that it would require the addition of 2 c.c. of normal alkali to make it neutral to phenolphthalein. Subsequently Hiss made various modifications of this formula, eliminating the unnecessary constitu- ents. The simplest combination, which was found to give excellent results, was made by adding 15 grains of agar and 5 grams of Liebig's extract to 1,000 c.c. of distilled water. No acid or alkali was added. The medium was cleared by the whites of two eggs and filtered through cotton. Plate cultures, made at 37° C, show excellent differentiation between the colonies of typhoid and colou bacilli in twenty- four hours. The former show threaded colonies, the latter do not. Hesse's Nahrstoff-Heyden Agar. — The "Nahrstoff- Heyden" is an albumose made from egg-albumin. It should first be stirred up in a beaker with a little water, and then added to the liquid. For cultivating the tubercle bacillus the medium consists of: 5 grams nahrstoff-Heyden, 5 grams salt, 30 grams glycerin, 10 grains agar, and 1,000 c.c. of distilled water; 5 c.c. of normal soda solution are added. The latter repre- sents a 14.3 per cent, of the crystalline salt t Xa t'0 3 + 1011,0) and not 28. G per cent., as stated by Hesse. The Hesse-Niedner agar, wdiich has been recom- mended for the study of water bacteria, is made by dissolving 7.5 grams of nahrstoff-Heyden and 12.5 grams of agar in 1,000 c.c. of distilled water. Gage and Phelps dissolve one per cent, each of agar and of the nahrstoff in 1,000 c.c. of distilled water, and make the solution neutral to phenolphthalein. Blood Serum. — The preparation of serum from small animals has been described at length under serum agar. When it is desirable to use large quantities of serum it is advisable to collect ox blood at a slaughter-house. The more care taken in collecting the blood under aseptic conditions the less troublesome will be the subsequent sterilization. A convenient receptacle is a half-gallon battery jar covered with paper and pre- viously sterilized. The spurting blood is received ssi) Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES directly into the jar, after which the paper cap is replaced and the blood set aside until it firmly clots. It can then be transported to the laboratory and set aside in a cool place for the serum to separate. The serum can then be drawn up by means of an aspirator into a sterile globe receiver, such as is shown as a part of Fig. 551. It can then be conveniently filled into test-tubes or into flasks. The earliest method of sterilizing blood serum is that of Koch by fractional heating. The tubes are placed in an inclined position in a serum coagulator shown in Fig. 548. The Roux water-bath, shown in Fig. 554, is particularly useful for this purpose. The serum tubes are immersed in the water at 58° C. and are heated for an hour at 58° C. on each of seven successive days. This low temperature is selected in order to accomplish the sterilization and yet keep the serum in a fluid condition. Unfortunately bacteria may be present in the serum which will actually grow at the temperature employed, and in that case this method of sterilization is inapplicable. Fig. 54S. — Koch's Blood-serum Coagulator. Some have endeavored to obviate this difficulty by filtering the serum through a Berkefeld bougie. Martin suggested that one to two per cent, of chloro- form be added to the serum, which is then set aside for several months, after which the chloroform can be driven off by heating at 05°. Fraenkel dispensed with the sterilization, relying entirely upon the asep- tic collection of the serum. When the serum is collected with the care outlined above, it will be found that very few bacteria are present. Consequently after the tubes have been filled with the serum they may be incubated for several days, and at the end of that time the contaminated ones can be discarded. This procedure is preferable to those just given. The sterile serum is then coagulated in an inclined position by raising the temperature of the sterilizer to 65° C, and keeping it there until the serum has become solid. The medium thus prepared is trans- parent and solid. When a higher temperature is used, the serum coagulates to an opaque white mass. Inasmuch as the above methods require much time and skill and are in themselves very tedious, they have been largely supplanted by fractional steriliza- tion in steam. For this purpose the tubes are first placed in an inclined position, either in a dry-heat oven, or, better, in the coagulator, and then heated to 85° to 95° C. until firm coagulation results. If this is not looked after, the medium will be torn up by gas bubbles during the next step. The coagulated- serum tubes are then placed in wire baskets and steamed, as in the case of agar, for half an hour on each of three consecutive days. The medium thus prepared is fully as useful as that which is transparent. LdJJlcr's Blood Serum. — This consists of one part of a one-per-cent. glucose bouillon and three parts 890 of blood serum. The mixture is filled into tubes and sterilized in the manner just given. It is used verv extensively for the diagnosis of diphtheria. Alkaline Blood Serum (Lorrain Smith). To each 100 c.c. of blood serum add 1.0-1.5 c.c. of a ten-per cent, solution of sodium hydrate, and shake gently" Place in tubes and sterilize as mentioned under blood serum. A clear solid medium results, consistine principally of an alkali-albumin. This medium i< also used in the cultivation of B. diphtheria Glycerin Serum.— Five per cent, or more of' glycerin is added as in the case of glycerin agar. The sterilize tion is the same as that just given. It is used fur the cultivation of the tubercle bacillus. Serum-water Media.— When serum is diluted with five to ten parts of water it can be sterilized by steam- ing without coagulation taking place. Hiss employed such a medium in differentiating between the pneu- mococcus and streptococcus; also in distinguishing between the dysentery and allied organisms He prepares the medium by adding one part of' clear beef serum to two parts of distilled water The mixture is first heated to 100° for a short time so as to destroy the glycolytic enzyme which is present after which one per cent, of the sugar desired is added' Dextrose, galactose, mannite, maltose, lactose sac- charose, inulin, and dextrin have been thus 'used The medium is colored by the addition of one per cent, of a five-per-cent. aqueous litmus solution The medium is then tubed and steamed for ten mini utes on three consecutive days. Marmorck's Media. — In order to maintain strepto- cocci at their maximum virulence Marmorek used several media, preference being given to them in the following order: 1. Human serum 2 parts, bouillon 1 part. 2. Pleuritic or ascitic fluid 1 part, bouillon 2 parts. 3. Serum of mule or ass 2 parts, bouillon 1 part. 4. Horse serum 2 parts, bouillon 1 part. These media can be sterilized by fractional heating at low temperature, or, better, by nitration through a Berkefeld bougie. Thalmann's serum bouillon for cultivating the gono- coccus has been mentioned in connection with his agar. Milk. — This is an excellent medium for diagnostic purposes. It is advisable to use centrifugated milk if possible. Otherwise the whole milk is placed in a beaker or flask and steamed for about half an hour. When partially cooled it can be poured into a large separatory funnel, or into a bulb receiver shown as part of Fig. 5072, and allowed to stand thus overnight. The underlying layer of fat-free milk can then be filled directly into tubes. These are then sterilized by steaming half an hour on each of three consecutive days. When time is an object the whole milk may be filled directly into tubes. If desired the milk may be colored with litmus. Instead of milk, whey may be used to good advantage. This can be pre- pared by coagulating the milk with rennet. The liquid is first separated by means of cheese-cloth and finally put through paper. It is then colored with litmus, filled into tubes, and sterilized. Care must be taken not to overheat the milk lest the lactose undergo more or less oxidation. Whey-gelatin and whey-agar are used for special purposes. Petrusehky's Litmus Whey. — Very dilute hydro- chloric acid is added to slightly warmed, fresh milk. The casein is precipitated and removed by filtration. The acid is just neutralized by the addition of dilute sodium hydrate solution, then the fluid is steamed for two or three hours, thus throwing out any acid albumin which might have been in the solution. The fluid when filtered off through paper should be just neutral and colorless. Litmus solution is added in sufficient quantity to give a distinct tint. Sterilize as in ordinary milk tubes. Urine. — By discarding the first portion of urine REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique which is passed, the remainder can l»> collected in sterile flasks and will l>c free from bacteria. Such urine may be used directly for studying the various fermentations which it may undergo. To prepare a urine gelatin the secretion should be diluted so as to have a specific gravity not to exceed 1.010. Ten per cent, of gelatin is then added, and when il dissolved the reaction is made to correspond to that of the original urine. Heller's urine gelatin is pre- pared in the same way, but has one per cent, peptone and a half per cent, of salt. After solution the Liquid is rendered faintly alkaline, then filtered and tubed. Piorkowski Urine Gelatin. — Normal urine of 1.020 specific gravity is collected for two days, and is allowed to become slightly alkaline in reaction. Then 1.5 per cent, peptone and 3.3 per cent, gelatin are added, and the mixture is heated for one hour on the water-bath, after which it is filtered and tilled into tubes. These are sterilized by heating at 100° ('. for fifteen minutes on the first day, and for ten minutes on the second day. The medium is used to differen- tiate the typhoid from the colon bacillus. Petri plates are made and developed at 22° C. for twenty- four hours. While the colon colonies are roundish, finely granular, sharp-bordered, and yellowish, the typhoid colonies are small and show a more or less marked threaded border. This method has given good results in connection with the examination of typhoid feces. Urine Agar. — This can be prepared by adding to the freshly passed urine two per cent, of finely cut agar. The mixture is then boiled until solution results, when it is filtered through cotton or paper as in the case of ordinary agar. This agar is then filled into tubes and sterilized by steaming. Another way of preparing a urine agar is to collect the urine, after discarding the first portion which is passed in a sterile flask, and then to transfer it by means of a pipette, as in the case of blood or serum, to the melted and cooled agar. One part of urine to two parts of agar is ordinarily used. Normal or albuminous urine may be used for this purpose, and with very little care the urine can be collected entirely free from bacteria. Such urine agar has been used to advantage for growing the gonococcus. Ox-bile Medium. — Conradi, Coleman, and Buxton, as well as others, have recommended ox-bile media in making direct cultural examinations of blood from typhoid-fever patients. Ox bile possesses certain advantages for this particular work since it prevents coagulation of blood, inhibits the bactericidal action of freshly drawn blood, and at the same time serves as an excellent culture medium for B. typhosus. Coleman and Buxton prepare their medium by adding two grams peptone and 10 c.c. glycerin to 90 c.c. ox bile. The mixture is placed in flasks of '20 c.c. each and sterilized. The blood (3 c.c.) from the patient is placed in flask, then incubated. The organisms develop rapidly, usually in from twelve to fourteen hours. Transplants are made to other media for further growth and diagnosis. Jackson's Lactose-bile Medium. — This medium has been found to be especially useful in the isolation of B. coli. and B. typhosus from water, milk, etc. It is prepared from undiluted ox-gall (or, an eleven per cent, solution of dry fresh ox-gall), to which is added one per cent, of peptone and one per cent, of lactose. The medium (40 c.c.) is placed in fermen- tation tubes and sterilized by the fractional method. The suspected water or milk is added in varying amounts up to 10 c.c. to the sterilized medium in the tubes. In this medium B. coli and B. typhosus rapidly overgrow other organisms; the B. typhosus may finally overgrow the B. coli. It is valuable as an enriching medium. Internal Organs. — For special use the several media, such as bouillon, agar, and gelatin, may be made up with the finely divided organs in place of the minced meat. At times the -olid organs •,,,• terilized and u-ed as such. For this purpose the spleen, li panel,., . brain, intestinal mucosa, etc., have I used. Matzuschita recommends their use in agar preparations (as a substitute for th, ■ beef) fop the pecial study of the flora of thi ,-,al. 'I"he steamed brain, for example, v. he,, cu( Up slices and sterilized, can I i for cultivating rele bacillu I er) and also the goi (Thalmann I. Egg Media.- Hueppe fir-t suggested tic use f fresh eggs as a culture medium. For this purpos, shell is thoroughly cleaned and disinfected with mer- curic chloride. A small opening j s then pun through the shell, anil through this the organism I,, lie tested is introduced into the inside. The opening is then sealed will, a bit oi t' rile pap, ,- and collodion. Another procedure is to insert through the opening in the shell a rather wide, drawn-,,,,1 tube pipette. On applying suction, especially with the aid of an aspirator, the contents of the egg can be drawn up into the bulb, and can then be distributed to t (Novy). The egg may be used as a solid opaque medium according to Wesener. The egg is thoroughly agi- tated so as to mix the yolk with the albumin. It is then coagulated at 75° to 80° C, after which the shell is removed and the egg is cut up into slices and placed in suitable dishes and sterilized by steam. In like manner the coagulated white of the egg may be cut up into slices and tubed. A transparent, coagu- lated egg albumin may bo prepared by converting it into an alkali albuminate, as suggested by Tar- chanow and by Karlinski. for this purpose the egg is placed in ten-per-cent. potash for fourteen davs, after which the shell is removed and the solidified egg is cut up into slices, tubed, and sterilized. Dorset's Egg Medium. — Dorset introduced this medium for the direct cultivation of /(. tuberculosis from tuberculous animal tissues; it is prepared from the whole egg alone or in Some instances with the addition of ten per cent, of water. It, was found that the whole egg content gave a more 1 satisfactory medium than either the white or the yolk, and that its reaction proved very favorable for the growth of the tubercle bacillus. The medium is prepared as follows: perfectly fresh eggs are cleaned, the shells sterilized, openings made at each end. then emptied into a sterile wide-mouthed bottle by carefully blow- ing out the contents. By gentle agitation a homogen- ous mixture is produced without causing any foam to arise. About 10 c.c. are placed in each "test-tube under aseptic precautions, then inclined in a blood- serum oven, where they are hardened at 70° C. Dorset states that this usually requires four to five hours each day for two days, and sterilization takes place at the same time. Before inoculation thr >r four drops of sterile water should be added to each tube, if the medium is dry, to supply sufficient mois- ' ture for growth. Lubenau's Glycerin-egg Medium. — This medium is composed of a mixture of a five-per-cent. glycerin bouillon (neutral or slightly alkaline to litmus) with wdiole egg contents. It is prepared by adding the contents of ten eggs to 200 c.c. of the glycerin bouillon. The same technique, as to sterility, etc., is employed in handling the eggs as mentioned above under "the Dorset egg medium. To the egg contents in a sterile flask, the sterile glycerin bouillon is added, and a homogenous mixture made by gently agitating. The medium is tubed, placed in slanted position in the blood-serum oven, and hardened at 70° (', the same as the plain egg medium (Dorset) already outlined. This medium also is used for the cultivation of tubercle bacilli. Potatoes. — These may be prepared in several ways. The old method, introduced by Koch, is still used where mass cultures are desired. The potatoes are 891 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES scrubbed clean under the tap, and any bad spots carefully removed by means of a knife. They are then placed in boiling water or steamed for three- quarters of an hour. By means of a knife, which has been sterilized in a flame, they are then cut into halves and placed in a large moist chamber or suitable pan provided with a lid. The bottom of this vessel should first be covered with a piece of filter paper which has been moistened with water or with mer- curic chloride solution. The cut and sterile surface of the potatoes can then be inoculated with the or- ganisms to be cultivated, either by spreading the material over the potato with a sterile knife or by making parallel streaks. Inasmuch as there are several sources of contamination in this method, it has been largely displaced by the modified procedures. In Esmarch's modification the potato is pared and cut into slices about a third of an inch thick, which are placed into small glass dishes about seven centi- meters in diameter and one centimeter high, known as Esmarch dishes. These are then sterilized by steaming in the usual way. The best way of using potatoes for culture purposes is that introduced independently by Bolton and Globig. The cleaned potato is placed in boiling water for about half an hour. By means of a cork- borer or a test-tube the end of which has been cut off, cylinders of potato may be punched out. The skin is removed from the ends of the cylinders, after which these are halved by a diagonal cut. The wedge-shaped semicylinders are now placed in sterile test-tubes and sterilized by steam. Another method which possesses certain advantages over the above consists of taking a large uncooked potato, punching out cylinders, and cutting wedges as just men- tioned. These wedges are placed in a suitable vessel and tap water is allowed to flow over them about twenty-four hours. This removes certain soluble constituents of the potato, which if allowed to re- main might discolor the finished medium after it has stood for some time. Also, the washing removes much of the acid which fresh potato contains. After re- moving the washed potato wedges from the running water, they are placed in Roux tubes and auto- claved at 120° C. for fifteen minutes. This cooks the potato and also sterilizes t h o r - oughly. Roux intro- duced a Fig. 549. — Roux Tube for Potato Culture. very use- A con- ful modification of the test-tube method, striction is made in the lower part of the tube, about an inch from the bottom. This compartment may be filled with water or, when cultivating the tubercle bacillus, with five-per-cent. glycerin. These tubes can be readily prepared from the ordinary test-tubes. A narrow blast flame is directed horizontally against the tube, which is rotated in a vertical position. The Roux tube is shown in Fig. 549. A good sub- stitute for this tube may be made by placing on the bottom of the test-tube a layer of absorbent cotton, which may be soaked with the glycerin solution. Glycerinated potato may be prepared by soaking the thoroughly washed, prepared potato wedges (see above) in a twenty-five-per-cent. solution of glycerin, from one quarter to one-half hour. Then they are placed in tubes and autoclaved at 120° C. for fifteen minutes. Mashed potatoes spread over the bottom of a flask have been used, but this offers no special advantage over the methods given. The preparation of potato gelatin with or without potassium iodide has already been described. Bread Medium. — Ordinary bread is toasted to a crisp, then powdered, in which condition it may be kept in stock. For use the powder is placed on the bottom of small flasks and thoroughly moistened with water, then sterilized by steaming. This me- dium is particularly useful for cultivating moulds. Plant Infusions. — These are useful for growing certain bacteria and also amebas. Infusions of hay straw, fruits, grains, etc., take the place of meat extract. By the addition of agar or gelatin, solid media may be prepared. Beer wort, either as such or as a gelatin, is valuable for the cultivation of yeasts. Protein-free Media. — With the exception of urine all the media described thus far contain some proteid matter. The latter, however, is not essential, for it is possible to grow bacteria on media which contain sulphur, nitrogen, and phosphorus in inorganic com- bination. Such a solution was used, for instance, at a very early date by Pasteur. It consisted of one part of ammonium tartrate, ten parts of candy sugar, the ash of one part of yeast, and 100 parts of water. The botanist Cohn employed a similar solution, con- sisting of 0.1 gram each of potassium phosphate and magnesium sulphate, 0.01 gram of tribasic calcium phosphate, 0.2 gram of ammonium tartrate, and 20 c.c. of distilled water. Naegeli's solution was made by adding 1 gram dibasic phosphate, 0.2 gram magnesium sulphate, 0.1 gram calcium chloride, and 10 grams of ammonium tartrate to 1,000 c.c. of distilled water. After the lapse of many years these non-albuminous fluids were again brought into use in a modified form by Uschinsky. His solution consisted of: Water, 1,000 parts; glycerin, 30-40 parts; sodium chloride, 5-7 parts; calcium chloride, 0.1 part; magnesium sulphate, 0.2-0.4 part; potassium phosphate, 2-2.5 parts; ammonium lactate, 6-7 parts; sodium aspara- ginate, 3-4 parts. Fraenkel's modification of this solution contains 5 grams of sodium chloride, 2 grams of potassium phosphate, 6 grams of ammonium lactate, and 4 grams of sodium asparaginate. These substances are dissolved in 1,000 c.c. of water and the solution is then rendered slightly alkaline. Similar solutions have been used by Maassen and by others. Thus Proskauer and Beck cultivated the tubercle bacillus on the following solution: Com- mercial ammonium carbonate, 0.35 per cent.; potassium phosphate, 0.15 per cent.; magnesium phosphate, 0.25 per cent.; glycerin, 1.5 per cent. For cultivating the nitrous and nitric-acid organ- isms Winogradsky employed wholly inorganic solu- tions. The nitric-acid producers were grown in a solution consisting of 1,000 c.c. of water, 1 gram potassium phosphate, 0.5 gram magnesium sulphate, 0.01 gram calcium chloride, 2 grams sodium chloride. This is filled into flasks in portions of 20 c.c. each, together with a little freshly washed magnesium carbonate. To these flasks, after sterilization by steam, 2 c.c. of a two-per-cent. solution of ammonium sulphate are added, after which they are incubated to eliminate contaminations. For the nitrous-acid organisms the solution consists of 1 gram ammonium sulphate, 1 gram potassium sulphate, and 1,000 c.c. of water. It is filled into flasks, magnesium carbonate added, after which they are sterilized by steam. As a substitute for gelatin Winogradsky employed silicic-acid jelly, which was added to solutions of essentially the same composition as those just given. 892 REFERENCE HANDBOOK OF THE MEDICAL SCIENl ES Bacteriological Technique A number of simple, synthetic i lia I ia \ . • been suggested for the isolation of B, coli in water analysis. Dolt has recommended two such media for this purpose, which he claims possess certain advantages over the ordinary standard lactose-litmus agar. They are prepared as follows: In one, a solution composed of 5 grams glycerin and 1 gram ammonium phosphate, dissolved in 500 c.c. distilled water, is used; in the oilier medium, 5 grams ammonium lactate and 1 gram disodium phosphate are substi- tuted for the above ingredients — the salts are dis- solved in the same volume of distilled water. In either case the solution is then added to 5(10 c.c. of three-per-cent. purified agar, and neutralized with sodium hydroxide, using phenolphthalein as an indicator; one per cent, of lactose i- added just before sterilization. One-per-cent. azolitmin (Kahl- baum) solution is to be added to the medium; this is prepared by adding one gram azolitmin to 1U0 c.c. distilled water, boiling for fifteen minutes, then ready for use. Standardization of Media. — The procedure as introduced by Koch, and still followed in many laboratories, is to add a saturated solution of sodium carbonate, in portions of a cubic centimeter or more, to the nutrient medium to be neutralized until a drop of the mixture, transferred by means of a glass rod, turns red litmus paper promptly blue. In some laboratories a strong solution of sodium hydrate is used in the same way. Obviously this method lacks quantitative precision, and the duplication of the same reaction in several batches of material is out of question. Moreover, it is an established fact that the reaction of a medium has a very important influ- ence upon the development of bacteria. For these reasons the bacteriological committee of the American Public Health Association, adopting Fuller's work, recommended the following method for the titration of nutrient media. The reagents necessary are: 1. Five-tenths-per-cent. solution of phenolphtha- lein in fifty-per-cent. alcohol. 2. Normal sodium hydrate (N. NaOH). A liter of this solution contains forty grams of NaOH. 3. Twentieth normal sodium hydrate ("NaOH). A liter of this solution contains two grams of NaOH. 4. Normal hydrochloric acid (N.HC1). A liter of this contains 30.5 grams HC1. 5. Twentieth normal hydrochloric acid (." IIC'l) . liter of this contains 1.825 grams of HC1. The preparation of these solutions requires some familiarity with the methods of quantitative analysis. The solutions can be built up by starting from a twentieth normal solution of oxalic acid or, better, succinic acid. The titration is carried out as follows: To 5 c.c. of the filtered medium in a six-inch porcelain evapo- rating-dish add 45 c.c. of distilled water and 1 c.c. of the phenolphthalein solution; boil for three minutes to expel carbonic acid, then run in the twentieth normal alkali, drop by drop, with constant stirring, until a bright pink color results. The number of cubic centimeters of the twentieth normal alkali required to neutralize 5 c.c. of the medium gives directly the number of cubic centimeters of normal alkali (i.e. percentage) required by 100 c.c. of the medium. Thus if 5 c.c. of the medium requires 2.8 c.c of " alkali, then 100 c.c. would need 56 c.c. ,": or 2.s"cc. of N. NaOH. The quantity of the medium remaining is now meas- ured and the amount of alkali needed for neutraliza- tion is calculated and added. After the addition of the alkali the liquid is boiled and a portion is then titrated as before. It should be neutral, and if it is not, as often is the case on account of unknown changes, the requisite amount of alkali to make it so is added to the bulk. The medium which is neutral with to phenolphthalein is very alkaline « ithn pect to litmus. Thus a bouillon which is neutral to litmus will re- quire about 25 C.C. of normal alkali per liter to inn I ■• it neutral to phenolphthalein. In general the addi- tion of in c.c. of normal alkali to a medium which is neutral to litmus imparl the most favorable di of alkalinity. Hence the optimum reaction with reference to phenolphthalein is obtained by adding 15 c.c. of normal acid to the liter of neutralized medium. It is customary to u e the ign I to indi- catean acid reaction, and — for one thai i.^ alkaline. Thus + 15 means (hat the rear-lion is acid with respect to phenolphthalein, and that one liter of the medium would require 15 C.c. of normal alkali for neutralization. The titration with litmus as an indicator is 1" i carried out in the following way: Port ions of ."> r.c. of the medium are measured out into each of four or five large test-tubes. In the case of bouillon the amount of ^alkali needed to neutralize this amount may vary from 0.3 to 0.0 c.c. Hence to lube 1 add 0.3 c.c; to tube 2 add 0.4 c.c; to tube '■', add 0.5 c.c, ele. The contents of each tube are 1 hen boiled for a minute, after which a slip of red and one of blue lit- mus paper an' dropped into the hot liquid and allowed to remain there for about a minute. The papers are then drawn out, side by side, on the walls of the tube when the colors can lie compared. In this way the amount of alkali necessary to neutralize 5 c.c. with respect to litmus can be determined. Bouillon, as well as agar, usually requires about .5 c.c per liter for neutralization while gelatin needs from MO to 35 c.c. Having determined the amount needed for neutralization, this amount, together with an excess of 10 c.c. per liter to impart a suitable alkaline reaction, is then added to the medium. Neutral red is sometimes used as an indicator to determine the reaction of media. It reacts sharply with weak acids and weak bases near the absolute neutral point. For ordinary purposes it is hardly necessary to resort to these rather complicated methods. It is sufficient to add directly to bouillon and to agar 15 c.c. of normal alkali per liter. Gelatin will require about 40 c.c. In general, sodium carbonate is pref- erable to the hydrate. Preparation and Filling of Tubes. — The cheaper grades of test-tubes should be avoided. They are very thin and therefore break easily, and, moreover, on heating they will often frost because of the separa- tion of silicic acid. The best test-tubes are the "blue-lined" or "resistant glass" quality, or those of genuine Bohemian glass. The size used varies with the purpose and the individual taste: 12X125, 15 X 150, and 20X150 millimeters are convenient. The new tubes of the better glass can be used after being swabbed out with warm water. The cheaper grades are very alkaline, and for that reason should be first soaked in very dilute warm hydrochloric acid, after which they should be rinsed or swabbed thoroughly in clean warm water; or what is still better, immerse the tubes for about one hour in the following cleaning mixture: 300 parts of a hve-per-cent. solution of potassium bichromate in water, to which is slowdy added 400 parts of con- centrated sulphuric acid while constantly stir- ring. This mixture removes all organic matter, and is especially useful as a cleaner for old glassware. The glassware is washed in running water to remove all traces of the acid. The cleaned tubes are allowed to drain, and when dry are plugged. Used tubes should be sterilized by steaming for a half-hour after which they may be filled with water and again heated, so as to bring the more or less dried contents into solution. The simplest way of plugging is to place over the S93 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Fig. 550. — Wire Basket for Sterilizing Tubes. mouth of the tube a piece of cotton, about two inches square, which is then pushed within by means of a narrow glass rod or a pair of smooth forceps. Such plugs answer all ordinary purposes. They are, how- ever, rather loose, and permit evaporation of the media, and cannot be used when the tubes are to be sealed with wax. A firm solid plug is made by taking a piece of cotton about three inches square. This is folded into thirds and _^ii^ : tSSSM then roll' 1 ' I up from the end into ^^^™^^^ra||j as firm a cylinder as possible. By a twisting motion the plug is inserted into the tube, and only enough cotton is left on the out- side to permit grasping of the plug. The plugged tubes are then placed in a wire basket, such as is shown in Fig. 550. These baskets are made of heavy galvanized netting. The usual size is twenty-four centimeters high and eighteen centimeters square. Smaller baskets, 10 X 12 and 18 centimeters high, are very useful. Cir- cular baskets of a size to fit the sterilizer are also used. Flasks, bulbs, etc., should be prepared for steriliza- tion in the same way. After the tubes have been sterilized by heating in the dry-heat oven at 150° C. for one hour, they are ready to be filled with the nutrient media. This can be done by the aid of a small funnel. When large quantities of media are to be tubed much time can be saved by using a large funnel or globe receiver, such as is shown in Fig. 551. The lower end of the bulb is connected with a drawn-out glass tube and is provided with a pinch-cock. In this way the media can be rapidly filled into the tubes. Another simple method con- sists in using the ordinary Flor- ence flask, containing the me- dium and securely fitting a two-bore rubber stopper in its mouth. Through one of the openings pass a straight thistle tube, of such length that it almost touches the bottom of the flask, and plug the external bulbular portion with cotton to act as an air filter. Through the second opening pass a straight glass tube about ten centimeters long so that it projects from two to three centimeters into the neck of the flask. To this tube attach a drawn-out glass tube, by means of a piece of rubber tubing, to permit the use of a pinchcock. For filling test- tubes the flask is inverted, and supported neck downward in a ring retort-stand of suitable size. This simple apparatus admits of complete sterilization intact together with the me- dium. But in such case the pinch-cock must first be removed to allow air or vapor a means of escape from the flask during the heating. By this method a sterile medium is ready for use as soon as prepared. Ordinarily the tubes are filled to the depth of one and one-half or two inches. In special cases in which definite quantities are desired, the simple apparatus shown in Fig. 551 can be used. The containers, Fig. 551.— Globe Re- ceiver for Filling Media into Tubes, with Burette Attachment. (Novy.) Fig. 552. — Treskow's Apparatus for Measuring Media into Tubes. with the media to be filled, can first be sterilized by steaming, after which the media can be measured out into sterile tubes, which will not require further treatment. A less desirable apparatus is that of Treskow, shown in Fig. 552. Sterilization. — By sterilization is meant the total destruction or removal of all organisms in or about a given object. This can be accomplished in a variety of ways. 1. By Direct Flaming. — This method is applicable for the sterilization of glass rods, slides, cover-glasses, platinum wiresj searing irons, and rough instru- ments. Valuable surgical in- struments would of course be damaged by this procedure. 2. By Means of the Dry-heat Sterilizer. — The form mosl often used is that of Koch, shown in Fig. 553. This is made of sheet iron, is double walled, and the outer wall may be lined to advantage with thick asbestos board. The form as shown is designed to sterilize not only tubes and flasks but also glass tubing, pipettes, and the like. The oven is used for sterilizing only glass and metal ware. It must not be used for sterilizing media. A temperature of 150 C. should be maintained for one hour. Usually it will be sufficient to allow the temper- ature to rise, and as soon as it has reached 200° C. the gas is turned off. The cotton should show a slight tinge of yellow after this heating. If the plug browns consid- erably and powders it is due more to the fact that the cotton has been chemically treated than to the heat. 3. Fractional Sterilization at 56°-5S° C— This method was introduced by Tyndall, and has been used for the sterilization of liquid serum, milk, and other fluids which are liable to be altered more or less by heat. It is based upon the fact that the actively vegetating forms of bacteria are readily destroyed as a rule by exposure for some minutes to this temperature. The resting forms or spores are not in the least affected by such exposure. It is necessary to wait until the spores have germinated into the vegetating forms, which can then be destroyed by a second like heating. As ordi- narily practised, the tubes are placed in an apparatus, such' as that shown in Fig. 554, and are heated for one hour at the given temperature on each of seven or eight consecutive days. This method sometimes gives good results, at other times it fails. The reason for this lies in the presence Fie,. 553 h's Dry-heat Sterilizer. Sill REFERENCE HANDBOOK OF THE MEDICAL BCIEN( ES 11.11 terloloclcal Technique It absence of the so-called thermophilic bacteria. 'licM- organisms actually grow best at the temperature mployed, and hence, if they chance to be present, he method is inapplicable. A temperature of 70° C. r**3 Fig. 554. -Rous Water-bath for Sterilizing Serum, with Metallic Regulator. may be used in like manner, but this causes coagula- tion of the serum. By pasteurization is meant the partial destruction of the organisms which are present in milk. This is accomplished by exposing the milk for half an hour, or more, to a temperature of about 68° C. (155° F.). While this temperature does not destroy the spores which may be present, it does kill the lactic-acid and other bacteria, which do not produce spores. As a result, milk treated in this way will keep for several days without coagulating. If a higher temperature is used, the taste of the milk is likely to be impaired. 3. Sterilization in Flow- ing Steam.— Several forms of apparatus have been devised for this purpose. Fig. 555. — Koch's Steam Sterilizer. Among the earliest is the well-known form which bears Koch's name. This apparatus is used almost entirely in Germany, and to a considerable extent in this country. It is shown in Figs. 555 and 556. It con i t of a cylinder of galvanized iron, or better of copper, which can be given such dimei may be desired. Ordinarily ii is about half a meter high ami about twenty-five centimeters in diameter. It is surrounded by a thick covering of fell M, to prevent loss of heat by radiation. In the interior of the cylinder at R i placed a grate whicl a a support for the pail and other ve els to be disinfected. The water in the lower com- part llli Ml i llealeil liy one or more large gas-burners. \l>n\e ii i closed with a cover I), which isalso covered with felt. A central opening permits 1 he escape of steam, and can be u ed for I he in sertion of a thermometer. The pail -hou □ to the right of t he sterilizer has a gral ing for a bottom, to allow free ai ess of the steam, and in it are placed the articles to be sterilized. The nutrient media are as a rule sterilized by steam. A single heating for one hour in steam at 100° C.ls usually sufficient to render the media sterile. Prolonged heating, however, tends to alter the media, and for that reason fractional or discontinuous sterilization is resorted to. The latter has the additional advantage that it renders the medium more surely sterile. can withstand steaming for one and even five or six hours, and if such forms chance to be present it is evi- dent that the material cannot be sterilized by the single heating for one hour. In the other procedure the media are steamed for fifteen minutes or half an hour, according to the nature of the medium, on each of three consecutive days. The first heat serves to destroy the vegetating germs that may be present. In Fig. 556. — Section of Koch's Steam Sterilizer. There are spores which Fig. -Arnold's Steam Sterilizer, Sectional View. the interval which elapses between the first and second heating, the spores which are probably present will germinate and are thus converted into t he much weaker form, which is then destroyed by the second steaming. The second interval allows any remaining spores, which may have failed to germinate the first day, a chance to do so, and the third heating is expected to dispose of these last organisms. As a rule all media S95 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES should be incubated for one or two days to make sure that they are perfectly sterile. If any growth develops in the tubes or flasks these should be discarded, and only those which are free should be preserved for use. Failure to secure sterilization by this procedure is due to one of the following conditions: The tempera- ture which prevails during the twenty-four-hour period which elapses between the consecutive heats may be so high that the spores which are present not only germinate, but the vege- tating forms in turn give rise to spores, so that a larger number of resistant forms are present on the second or on the third day than were present in the begin- ning. Again, it may happen Fig. 55S. — Novy Steam Sterilizer. that the temperature is too low, in which case the spores cannot germinate, and hence will be found to resist sterilization. Another source of error, though much less common, was pointed out by Smith. If the spores of anaerobic bacteria are present in a bouillon, they cannot from their very nature germinate under the ordinary conditions, that is in the presence of the air, and may therefore escape de- struction. In this country and even in Ger- many, the Arnold steam sterilizer has met with a very favorable re- ception. The apparatus is shown in Fig. 557. It consists of: (a) a flat, shallow boiler, holding but a small amount of water, and therefore requiring but a minimum amount of heat to produce steam; (6) a reservoir placed upon the boiler, which it constantly feeds and insures the con- stant formation of steam; (d) a covered steam chest or receiving vessel, placed above the reservoir and connected with the boiler by a cylindrical tube of large diameter (c); and (c) a hood, covering the re- ceiver and en- closing an air space, which is constantly sup- plied with es- cape steam. The hood and the steam jacket which it encloses prevent variations in temperature in the receiving vessel so long as the heat applied to the boiler remains unchangi d. A cheap and thoroughly efficient steam sterilizer Fig. 5. r »n. — Ohamberland Autoclave for Ster- ilizing by Steam under Pressure. (Novy-) adapted for individual work is shown in Fig. 558. This consists of an ordinary Hoffmann iron water-bath ten to twenty centimeters in diameter. On this is placed a copper pail (20 X20 cm.), which is provided with a perforated bottom. Two perforated rings on the inside allow the passage of steam, and prevent the cotton of the tubes from coming into contact wit h the side of the steamer. The tubes filled with media are placed in the pail, and this is then set on the water- bath, the water of which has been previously raised to active ebullition. In a few minutes steam will issue from the tube in the top of the cover. It is always advisable to take the temperature of the vapor as it issues from a sterilizer and to count the time of exposure from the moment that the vapor actually shows the temperature of steam, that is 100° C. 4. Sterilization by Steam Under Pressure. — This pro- cedure is used almost entirely by the French workers. Its usefulness is such as to merit a wide introduction into this country. The apparatus, which is designated as an autoclave, is shown in Fig. 559. It consists of a strong boiler, in the bottom of which a small quantity of water is placed. The articles to be steamed are placed in a wire basket, which is set on the bottom of the boiler. The lid is closed with a rubber gasket and securely held in place by thumb-screws. Inasmuch as the amount of aque- ous vapor in a given space, as well as the temperature, in the case of confined steam, is greater than with flowing steam, it follows that the autoclave is considerably more efficient. Thus steam at 130° C, under pressure, will destroy instantaneously spores which would resist flowing steam at 100° C. for five or six hours. The culture media can be sterilized by a single heating for fifteen to thirty minutes at 110° C. A higher temperature should be avoided, as it tends to alter the reaction of the-media. Glass apparatus, filters, rubber, etc., can be sterilized by heating at 120° C. for half an hour. In- fected animals can be subjected to 120° C. for the same length of time, or to 130° C. or more for a less period. It must be remembered that the autoclave requires more care than an ordinary sterilizer owing to the danger of explosion. The following points should be observed in its use : Enough water should be present; after the burners are lighted, the steam valve should be left open until the air has been expelled ; when the steam has flowed rapidly for one or two minutes the valve is closed; as soon as the de- sired temperature is indicated on the gauge, the burners are turned down, so that this temperature is maintained for the required time; the burners are then turned off, but the steam valve is not opened until the temperature has fallen below 100° G, after which the lid can be removed. The safety valve should be tested to open at about 125° C. It is a good rule not to leave the autoclave out of sight while the fi G . 560— Pnsteur-C'ham- temperature is rising. berland Filler. Obviously this piece of ap- paratus can also be used as a steam sterilizer with temperature at 100° C. In such case the steam valves above are opened and the water is heated to the boiling-point. If steam is generated more rapidly than it can make its exit, the pressure rises, conse- 896 REFERENCE HANDROOK OF THE MEDICAL SCIENCES ll.ii ii-rluliiuli ,.l Tpclinlciun guently the temperature goes above loo" ('. There- fore boil gently or raise cover enough to allow free escape of I he steam. .".. Sterilization by Filtration. — It is possible to remove completely all the organisms which may be present, in a liquid by filtration. Filler paper, of course, on account of the small size of the bacteria, cannot be used for this purpose. There are only two reliable filters for bacteriological work. That known as the Pasteur-Chamber- land filter is the best, and is made of unglazed porcelain. The form as used for filtering water for domestic use is shown in Fig. 5G0. The original French filters are to be preferred to the German imi- tations. They are made in two grades; that marked F is more porous than that marked B. The Kitasato filter, a narrow form of the above, is also made of unglazed porcelain, and is in- tended for the filtration of very small amounts of liquid. This can, however, be done also with the larger filter. It is shown in Fig. 561. The Berkefeld filter (Fig. 565) consists of closely packed in- fusorial earth. It can be ob- tained in several sizes, having the general shape of the Pasteur- Chamberland bougie. It is considerably more porous than the porcelain filter, and is therefore adapted for rapid filtration, but it should be borne in mind that it is more likely to allow the passage of bacteria. A useful form of apparatus for holding the Pasteur- Chamberland bougie, that of Martin, is shown in Fig. 56'J. It consists of a metal cylinder with a funnel-shaped top, which permits the filtration of the culture through filter paper previous to its passage through the bougie, and thus obviates or lessens the clogging of the latter. A rubber ring serves to make Fig. 561. — Kitasato's Filter. Fig. 562.— Martin's Filter. a tight joint when the bougie is held in place by the lower screw cap. The lower end of the bougie is connected with a piece of vacuum rubber tubing to a globe receiver. The entire apparatus is sterilized by heating in an autoclave. The filtration may be carried on by gravity, or an aspirator may be connected with the upper tube of the globe receiver. When Vol. I. — 57 the filtrate is o> be transferred, the drawn-out aide tube is scratched near the end with a file, and then broken off, after which the tube is (lamed and the liquid is drawn off into sterile tubes or flasks. This globe receiver can be used until the drawn-out tube is too short, when a new lube is fused on. A better form of a globe receiver is shown in Fig. 565. This is provided with three side tubes, which arc plugged with cotton, after which the receiver is sterilized in a dry-heat oven. When it is to be used, the cotton is removed from the tube D, which is then connected with the sterile bougie by means of a piece of sterile vacuum tubing. The horizontal tube F is similarly connected with t he sterile drawn-out glass tube G. The tube E, with its cotton plug in place, is connected with a Chapman pump. The filtrate may be withdrawn by means of a sterile bulb pipette, or in the same way as from the receiver of Martin. The advantage lies in the short rubber tubing, compactness, and the convenience in attaching the Fig. 563. — Novy's Filtering Apparatus. drawn-out tube. This vacuum receiver can be ob- tained in several sizes, such as one-quarter, one-half, one, and one and one-half liter capacity. Instead of a metal cylinder to hold the bougie, Novy has devised one of glass. This is shown in Fig. 563. The necessary tight joint between the bougie and the glass cylinder is made with a rubber ring, and the bougie is brought up tight into place by means of small vises, which act on the flange and on an iron washer. The arrangement is shown in Fig. 564. If desired the liquid can be filtered under pressure, in which case the rubber stopper at H is connected with a tank of compressed air. The Fig. 564- Conneetions for the Novy Apparatus, rings; 4, iron washer. 1, 2, 3, Rubber cylinders are made to withstand a pressure of over 100 pounds. The Berkefeld filter may be attached to the above glass cylinder by means of a rubber and iron washer and the clamps mentioned (Fig. 565). A more con- venient arrangement is to use a cylinder of brass of suitable length and width, threaded at each end. The lower end is provided with a screw cap, through 897 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES which the metal end of the Berkefeld bougie is passed. The upper end is also closed with a screw cap, provided with a three-eighths of an inch nipple, which serves to connect the cylinder with the compressed air. The tip of the Berkefeld is connected with a globe re- ceiver. The filtration can then be carried out by gravity, by aspiration, or by pressure. The filtration of liquids constitutes an exceedingly important part of bacteriological technique. By its means the soluble products of bacteria may be separated from the solid cells. In this way the toxins of many pathogenic bacteria are prepared. Again it is by the nitration process that it has been possible to demonstrate the existence of the so-called ultrami- croscopic organisms. While the common bacteria will not pass through a filter, there are a number of diseases in which the germ is so minute that it will go through the Berkefeld, and, at times, even through the Pasteur-Chamberland bougie. Yellow fever, sheep-pox, foot-and-mouth disease, contagious pleuropneumonia of cattle, chicken pest, rinderpest, horse sickness, molluscum contagiosum of birds, and the "mosaic disease of to- bacco" are of this class; so also is rabies. The fact that a given filtrate infects is not proof that the cause is always in this extremely minute form. It may be that the real organism is relatively large, as in the case of the rat trypanosome, and yet Berkefeld filtered cultures of this will often infect animals. This is due to the existence of a minute stage in the develop- ment of the organism. It is therefore to be expected that the pathogenic pro- tozoa, though they themselves may be large, may give rise to filterable sporo- zoites. 6. Sterilization by Chemicals. — This principle is applicable only to a limited extent to nutrient media. The addition of such substances as carbolic acid or mercuric chloride will serve to destroy the organisms which may be present; but since these compounds can- not be removed from the medium, it follows that it cannot then be used for culture purposes. A few substances have, however, been used with this object in view. Thus if chloroform is added to milk or blood serum, and is allowed to act long enough, it will bring about sterilization. The remaining chloroform can finally be driven off by means of gentle heat and by aeration. Ether has been used in the same way, and indeed this is a useful procedure for sterilizing such weak cultures as those of cholera. Glycerin, as is well known, is added to vaccine with the ob- ject of destroying the common pus-producing organisms which are so often present. It cer- tainly will in time destroy all of these accidental bacteria, but, unfortunately, prolonged exposure of the vaccine virus to the glycerin damages it as well. Chemical disinfection of drinking-waters has also been proposed, especially in connection with military operations. For this purpose various substances, such as bromine and the organic peroxides, have been suggested. In the laboratory this method is resorted to more or less io sterilize old used cultures, test-tubes, and animals. Five-per-cent. carbolic acid or 0.1-per- cent, mercuric chloride is employed. 898 The Incubator. — It is customary to divide bacteria into two large groups — the saprophytic and the parasitic — according as to whether they grow in nature on dead matter or in the living body. Among the latter are classed the disease-producing bacteria. In general the optimum temperature for the growth of the saprophytic organisms is about 25° C. (77° F.). whereas the pathogenic bacteria thrive best at the temperature of the body. In order to supply this requirement it is necessary to use an incubator or Fig. 565. — Berkeield Filter showing Manner of Attachment to Globe receiver. (Novy.) Fig. 566. — Koch's Incubator. thermostat, the temperature of which can be main- tained without variation at any desired level. Vari- ous forms of apparatus have been devised for this purpose; that of Koch is shown in Fig. 566. It consists of a double-walled box of copper, the sides and top being covered with felt. The space between the walls is filled with water. In the top is an opening communicating with the interior air space, and in it a thermometer is placed to indicate the temperature. The openings in the corners com- municate with the water space. One of these is intended to hold a thermoregulator, while the other serves for the addition of water. Inner and outer doors are provided, and in the better models provision is made for ventilation and for keeping the air moist. The apparatus may be heated with an Argand burner. The ordinary Bunsen burner is not used because of the danger of "shooting back." The Koch safety burner is to be preferred, for it automatically shuts off the supply in case the gas should by any chance Fig. 567. — Koch's Safety Burners. happen to be turned off. It consists of two iron spirals w-hich, as they are heated, expand, and in so doing communicate this motion to an arm which then swings under and supports the weighted lever of the valve. If by any accident the flame should become extinguished, the spirals cool and contract; this causes the supporting arm to swing out from under the lever, which then falls and thus shuts off the gas (see Fig. 567). In case gas is not available the incubator is heated with an oil lamp. The Sartorius model is especially REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique well constructed for this form of heating. A good substitute can always be found in the ordinary egg incubator. In a few places the heat is supplied by means of electric hot plates. By far the most important accessory to an incubator is a thermoregulator, which will automatically control the supply of gas and hence the temperature of the oven. Several of the more common forms are shown in Figs. 568-571. The Reichert form, though very widely used, is far from being the most satis- factory. The lower bulb is filled with mercury, which as the temperature rises shuts off the opening through which the gas enters. In order I.. prevent the flame from being extinguished a minute opening is made in the gas-delivery tube whereby a minimum flame can be maintained. Fig, 56S. — Novy's Thermo- regulator. Fig. 569.- -Reichert's Thermo- regulator. In the Bunsen form the lower compartment is nearly filled with a mixture of equal parts of ether and absolute alcohol, after which a sufficient quantity of mercury is added to act as a valve. The upper part is closed with a stopper, through which passes the gas tube. When the proper temperature is reached, this tube is pushed down till the gas flame drops. The minimum opening prevents total extin- guishment. By careful manipulation the regulator can be set at any temperature which may be desired. In both the Novy and Dunham forms the lower bulb is filled with absolute alcohol. As this expands it acts against a column of mercury, which in turn shuts off the supply of gas. The lateral screw per- mits the adjustment of the regulator to the desired temperature. In the former the minimum supply can be regulated to a nicety. This enables it to be used for a water-bath, or for a small or large incuba- tor. It can be obtained with the alcohol cylinder of different sizes, according to the use for which the apparat us is intended. The metallic regulator of Rous is intended for controlling the temperature of large water-baths and of incubator r , for which pure etter de\ ice can be found. It i made in tl "' , Fig. 570. — Dunham's Thernio-regulator. Fio. 571. — Bunaen'a Thermo-regulator. the straight and the U-shape, shown in Fig. 572. It consists of two metal bands having different coefficients of expansion. These are soldered toget her the full length. As the temperature rises, the free upper arm moves from and thus releases a spring valve, which shuts off the main supply of gas. A minute opening serves to supply a minimum amount of gas, and thus prevents extinguishment of the flame. dlib.'i >Amt . 1"'' ''■' -•-■ ■ ■■'■ ! '^ | Fig. 572. — Rous Metallic Thermo-regulator. The incubator described in its several modifications answers all ordinary purposes. In large laboratories it can, however, be dispensed with almost entirely, and its place is taken by the incubator-room. By this is meant a re. nn, usually about eight feet cube, which is maintained at a constant temperature. 899 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES This arrangement was first employed at the Pasteur Institute, where the heat is conveyed to the room by means of large pipes along the wall, filled with water, or better with glycerin. The circulating liquid is heated by a small gas stove placed on the outside of the room. A more simple and thoroughly efficient procedure is to place a small gas stove in the center of the room. Fig. 573. — Moitessier's Gas-pressure Regulator. This stove, which can be obtained of the French dealers, is so constructed that the gases of combustion are carried out of the room into a flue. Another procedure of limited application is to heat the room with steam coils. The regulation of the heat in this case is accomplished by means of an automatic steam valve operated by compressed air. The construction of the room requires no special care. The walls, whether of brick or of plaster, should be given several coats of white zinc. Shelves, water, gas and electric light, and a window should be provided. The regulation of the temperature in the rooms heated by gas is done by means of the Rous U- shaped regulator. All the connections should be of Fig. 574. — Murrill's Gas-pressure (Novy.) Regulator. Cross-section. metal to lessen the chances of fire. In order to have a temperature record it is advisable to place in the room a thermometrograph, the best form of which is made by Richard Freres, of Paris. Gas-pressure Regulator. — The best results with any form of thermoregulator are obtained when the gas pressure is constant or nearly so. When the varia- tion is considerable it is advisable to pass the gas through a pressure regulator before it reaches the thermoregulator. There are several forms of ap- paratus for this purpose. The Moitessier regulator is shown in Fig. 573. It consists of a cylinder A which is filled to the level of G with a mixture of equal parts of glycerin and water. On this is floated the metal shell B. The gas is admitted to the in- terior of B, through the tube K, the pressure being indicated by the manometer P. The gas flows into B until it is filled, when it raises it up and shuts off the supply of gas by closing the valve D. The pres- sure on the burner is regulated by the weights placed in the pan H, which is connected with B by the rod G. The amount of pressure on the burner is indicated by the manometer on the left of the apparatus. The burner is connected with the apparatus by means of a rubber tube attached to /, and the height of the flame is regulated by the stopcock M. A cheaper and more simple regulator is that devised in Novy's laboratory by Murrill and shown in Fig. 574. The gas passes into a cylinder which floats in liquid petroleum and leaves by two tubes at the bottom, one of which is connected with the thermoregulator, the other with a manometer. The cylinder is weighted so as to give the desired pressure to the outflowing gas. During the hot summer months it is desirable to have an apparatus which will keep a fairly constant low temperature, below that which would cause the gelatin cultures to melt. There are incubators con- structed for this purpose which furnish a supply of ice-cold water when the temperature rises above a given point. If the temperature drops too low, the electric lamp is turned on. When the temperature of the water as it leaves the ground is about 15° C. (59° F.) it is possible to use the simple apparatus shown in Fig. 575. This is made of galvanized iron. The inner box is held in place by means of a couple of stout rods. The water enters at the bottom through the small tube, which stops short on the inside of the outer box. The water then Fig. 575. — Novy's Low-temperature Incubator. flows under and around the inner box, and eventually reaches at the farther end the wide outflow tube. The end of t"his is turned up and is provided witha short piece of rubber tubing. By moving this up or down the level of the water in the box can be regu- lated. By regulating the flow of the water it ispossible to maintain a fairly constant temperature in the inner compartment. The Methods of Cultivation. — The fundamental basis of bacteriology may be said to be the fact that it is possible to cultivate artificially, and that in pure condition, nearly all of the known forms of bacteria. Until methods had been devised for this purpose it was not possible to determine definitely the part played by any organism either in the ordinary 900 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique phenomena of fermentation or in the more mysteriou processes of disease. To arrive at a demonstration of the causal relation of a given organism to the change which it is supposed to induce it is necessary to do two things: First, I he organism must be isolated in pure culture; and second the pure culture, once obtained, must be maintained by transplantation. The pure culture thus kept up through a series of transplantations, or generations as they are called, can then be tested upon animals to see if it will produce the disease, or upon suitable media to ascer- tain if it will cause the kind of fermentation, the pigment, or the light which it is supposed to produce. By a pure culture is meant one which is derived from a single cell. A given bacterium, small as it is, multiplies by division, and thus gives rise to two new individuals. These in turn grow and divide, yielding four cells. This process is kept up till many millions of organisms constitute the offspring of a single cell. Inasmuch as the division of bacteria is very rapid under favorable conditions, many dividing every half-hour, it follows that in a few hours a visible growth may be seen where at the beginning but a single cell was present. If the medium in which they are growing is liquid, it will usually become cloudy because of the disseminated bacteria. The early methods of cultiva- tion, as employed by Pasteur, made use of liquid media. Under these conditions it was exceedingly difficult to obtain pure cultures, and indeed it was largely a matter of chance and patience. Suppose that a given liquid contains two kinds of bacteria; in order to separate ra W ™ iff™ tnese so as t° have a single cell II as a starter for the pure culture it would be necessary so to di- lute the liquid that in all prob- ability a drop, or a cubic centi- meter would contain but one cell. This small quantity would then be taken and transferred to a sterile medium, and in this way it would be possible to obtain presumably pure cul- tures. Failure, however, was necessarily frequent and the element of doubt always re- mained. The introduction of the nutrient gelatin by Koch made it possible to secure pure cultures with the greatest of ease. All that was necessary was to inocu- late the liquefied gelatin with the mixture of bacteria, and after thorough agitation so as to separate each cell from its neighbor, to pour the liquid on to the surface of a sterile plate. The gelatin now solidifies, and imprisons, as it were, the separated cells. Each of these now multiplies and reproduces its kind; eventually, in the course of a day or two, a small growth, perhaps of the size of a small pinhead, appears. This is called a colony, and since it is derived from a single cell it constitutes a pure culture. Such is the principle of the dilution method for obtaining pure cultures. The isolation once accomplished, all that is necessary is to transplant the colony to sterile culture media so as to keep up the growth. The transferring of bacteria is usually done by means of a platinum wire. The wire, which should be about two inches long and fairly stiff, about No. 21 in size, is fused into the end of a glass rod. According to the object in view it is either straight, bent, or is provided with a loop as shown in Fig. 570. 576. — Platinum Fused in Glass At times a bunch of very fine platinum wires at- tached to a holder, the so-called Kruse's brush, is u -l to spread the material over tin- surface of the media. A glass rod bent at right angles is also very useful for i his purpose. The Roux spat ula of nickeled steel was first employed for the purpo e of transplanting bits of diphtheritic membrane to the culture lube. A similar spat ula made of thick iron wire is extremely useful for transferring moulds and coin pact growths, such as that of act inomyces. The Nuttall platinum spear is particularly useful for transferring bits of tissue, blood, etc., to the nutrient media. These two instruments are shown in fig. 577. The transferring of liquids, in large or in small quan- tities, can best be done by means of drawn-out glass tube pipettes, as is practised by the Pasteur School. This technique is at once simple and invaluable. The preparation of these pipettes will be understood from Fig. 578. The glass tubing, which has a diameter of about eighl millimeters, is cut up into lengths of about twelve inches. By means of the blast lamp a slight constriction is made at about two inches from each end. This serves to prevent the cotton plug from falling down, and also tends to keep the liquid from reaching the cotton. The ends of each tube are then care- fully rounded out in the flame. A piece of cotton is then pushed into the end of each tube. The tubes thus prepared (Fig. 578, a) are then sterilized in the dry-heat oven, after which they may be stowed away for future use. Whenever it is desired to make a pipette, one of these tubes is heated in the middle in a blast flame, and when the glass has thoroughly softened, the two halves are slowly drawn apart. A rela- tively wide, thick-walled capillary, about sixteen inches long, is thus obtained (Fig. 578, 6). This is then sealed in the flame in the mid- dle, and the result is two pipettes. For transferring large quantities of liquid a bulb is blown in the pipette (Fig. 57S, e). This is made by directing a narrow blast flame against the tube, which is at the same time rotated. As the glass softens the ends are slightly pushed together, so as to form a thick ring of glass. This is repeated once or twice. Finally a large blast flame is turned on, and when the thickened glass is perfectly soft, the end is brought into the mouth and the bulb is blown. The glass should be rotated during this operation, and in fact in all work of this kind. To use a pipette, the mouth end should first be rolled for a few seconds in a flame so as to insure sterility; the capillary end is then scratched with a file and the tip is broken off, after which the capillary is flamed. As soon as the tube has cooled, which fact can be ascertained by blowing through the pipette against the back of the hand, it is ready for use. The closure of the pipette when it is filled with the liquid is effected by means of the tongue pressed against the upper end. The great value of the pipette lies in the fact that it can be made in a few minutes, and can be used to transfer liquids from one tube to another, for drawing blood from the heart, fluids from the cavities, etc. It is indeed even more useful than a platinum wire. Plate Cultures. — Solid media, such as gelatin or agar, 901 Fig. 577. — a, Itoux spatula; b, Nuttall's platinum spear. Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cither plain or modified, are employed for this pur- pose. The starting-point in this method were the slide cultures used by Koch in his early investigations. The liquefied gelatin was poured upon the surface of sterile glass slides, which were levelled and kept cool by means of the apparatus shown in Fig. 579. The lower dish was filled with ice-water and the whole @S= Fig. 57S. — Pasteur Pipettes, showing Method of Preparation. (Novy-) was set true by the aid of a small spirit-level. A series of parallel streaks was then made on the solid gelatin by means of a platinum wire, which was dipped in the material to be planted. A number of slides were thus made, after which they were stacked on glass benches (Fig. 5S0), and placed in a moist chamber to develop (Fig. 581). The first streak, i Fig. 579. — Koch's Levelling Apparatus. on account of the large number of organisms planted, would probably yield a continuous solid growth. The next streak would have fewer germs, and the succeeding ones si ill less until eventually only single germs would be deposited, separated by an appre- ciable distance from the following ones. Wherever a single organism was deposited, as a result of multipli- 5N,u. — Glass Benches and Culture Slides. cation, a colony would soon make its appearance. (See Plate XII., 18) The slide method was soon improved by substitut- ing larger glass plates ( 10 x 13 cm.). Instead of mak- ing streak dilutions as just given, the gelatin was lique- fied, inoculated, and poured out upon the sterile plates, which were cooled on the plating apparatus. This method of plating may be used when the special Petri dishes, ordinarily employed, are not obtainable. The fact that the method required a lot of apparatus, slides, slide-box, levelling apparatus, ice, moist chamber, etc., as well as the fact that contamination from the air and from the dripping of the superposed plates was unavoidable, led Petri to introduce the modification which has almost entirely supplanted the older method. Gelatin Petri Plates. — In this * =s —^-^.-^m l nr > a method, as in the preceding, the gelatin is first melted by / immersion in warm water for a few minutes. By means of a sterile, looped, platinum wire a small quantity of the ma- terial to be examined is trans- ferred to a tube of liquefied gelatin, marked 1. By means d of the wire the material is thor- oughly mixed with the gelatin. Another tube, marked 2, is then placed beside the first, from which three loopfuls of gelatin are carried over to tube 2, with the contents of which they are well mixed (Fig. 582). A third tube, marked 3, is then placed beside number 2, and three loopfuls of gelatin are transferred from tube 2 to tube 3. It is evident from this procedure that even if the first tube received a million germs the second tube would contain only a small fraction, and Fig. 581. — Moist Chamber with Stacked Plates. the third tube would contain still less. The platinum wire must of course be sterilized whenever an inocu- lation is made into a new tube. A number of Petri dishes (Fig. 583), which are ten centimeters in diameter and one centimeter high, are Fig. 5S2. — Method of Holding the Tubes when Making Dilutions. previously sterilized by heating in a dry-heat oven for one hour at 150° C, or for a few minutes at 200° C, and allowed to cool. To pour the plate, the cotton is removed from one of the tubes, and the open end is rolled for a few seconds in the flame so as to sterilize it. 902 HKKKlil'AVi; iiwdii s h\ Tin; \| i; [ >|< ' \ |, scillXCES Bacteriological Technique In a few seconds the end of the tube becomes cool, after which the contents are poured oul into the Petri dish. The lid of the latter is removed just sufficiently l<> allow the gelatin in !»■ introduced By tilting, the gelatin is thru spread all mw the bottom of the dish. The latter is then sel aside in a cool place for the gelatin to set. With a g I gelatin this will take place even in the ordinary room within a few minutes. The remaining gelatin tube are poured in the same manner. Each plate should be numbered to correspond to the tube from which it was made. They should be marked also with the date and the kind of material used. A Faber 1 colored wax pencil is used for this purpose. Agar Petri Plates. — Inasmuch as gelatin melts at about 25° C. it follows that the method just gi\en cannot be used when the organism requires the temperature of the incubator. In such cases it is necessary to resort to the use of agar. The nutrient agar is first melted by heating in a water-bath at 100° C. The flame is then turned out and the tubes are allowed to cool in the water-bath until a tempera- ture of about 45° C is reached. The agar solidifies at about 40° C, and consequently the dilution must be made rapidly and the plates poured before that point is reached. Dilution cultures are made in the same way as just given for gelatin. The three agar tubes are then poured out into the corresponding sterile Petri dishes. The agar promptly solidities, and for that reason the spreading of the agar over the bottom must be hastened. The agar plates are then set aside to develop either at the temperature of the room or at that of the incubator. Esmarch Roll-tube Culture. — This modification of the plate method does away with the use of any special container other than, the test-tube. The dilutions in gelatin are made in the usual way. 9 : . \ Fig. 583.— Petri Dish for Plating. According to the original directions the cotton plug was cut off short, and the end of the tube was covered with a close-fitting rubber cap. The tube was then immersed and rotated in an almost horizontal position in ice-water. The gelatin solidified in an even film over the inside of the test-tube (Fig. 584). A more convenient way of rolling the tubes was devised by Booker. With the aid of a large test-tube filled with warm water a groove is melted into a block of ice. The gelatin tubes are then rolled in this groove until the gelatin solidifies in a smooth, even film. Nuttall has modified this procedure by replac- ing the ice block with a marble block provided with grooves for the test-tubes. Running tap water serves to cool the tubes. If the tubes are not rolled smoothly they can be softened by gentle warming and be rerolled. < toe advantage of this method lies in the fact that desicca- tion can be retarded more than with the other methods. Air contamination is likewise diminished. On tin- other hand, the presence of a few liquefying bacteria may spoil the tube. The Esmarch roll tubes should be kept in a cool place to prevent melting. When the colonies develop they may be examined by placing the tube on the stage of the microscope. To transplant the colonies a platinum wire, pro- vided with a hook, as shown in Fig. 576, should be used. Shake Cultures. — Dilutions are made in gelatin or V* agar as heretofore de cribed, I are 1 hen solidified in an upright position and I to develop. If it is desired to trait plant a given colony I he te i tube I d bi cral ehed n it h a dia mom about the level of the colony. On touching the scratch with a hot rod the crack can be led around the tube, after which the t wo part can bi eparated. Bj means of a sterile knife the medium can be cut ami i In- colony expo ed. In t he i i ol i •• t he entire cylinder of agar can be forced out of the tube into a sterile di h l>\ the cautious application of a Same to I he loner end of the t ube. The method offers a convenient means of determin- ing whether or not the organism planted generates gas. If such is the ease gas bubble- will make their appear- ance in the medium. As will be seen later this method is also use- ful in connection with the cultiva- l ion of anaerobic bacteria.. Streak CultiiriK. This proced- ure, w hich is essentially the same aS that Used by Koch in his slide cultures, is very frequently made use of at the present time. Thus, sterile gelatin or agar may be poured into sterile Petri dishes, and after the material has solidi- fied a series of parallel streaks may be made with an infected platinum wire or platinum spatula. The Kruse platinum brush maybe used to spread the organisms over the surface. A narrow glass rod, bent and flattened at the end, has been used for spreading gonorrheal pus over plates. Cotton swabs are used for the same purpose in the case of diphtheria. As in the case of the Esmarch roll tube, the Petri dish may be omitted in this method. In that event the gelatin or agar is melted and allowed to solidify in an in- clined position. The streaks are then made on the surface of the inclined medium. Potato tubes are inoculated in the same way. (See Plates XI. and XII.) To obtain perfectly isolated colonies by this method the same wire should be used to make parallel streaks on each of four or five tubes. When the colonies develop, trans- plantations can be made by means of a bent. wire. Hanging-drop Cultures. — A con- cave or well slide, shown in Figs. 599 and 600, is used. The cover- glass must first be sterilized by passing it several times through a "*■-'.— - flame. A large drop of sterile Fig. 584. — Esmarch 's bouillon is then placed in the mi- Roll Culture, ter, and this is inoculated with the germ to be studied. The slide with a ring of vaseline is then inverted and brought down upon the cover- glass, after which the preparation is turned over. Care must be taken to see that the vaseline closure is perfect. This method of cultivation is used to study the multiplication of the bacteria under the microscope. Hanging-block Cultures. — In order to be able to study the morphology and the multiplication of the diphtheria bacillus to better advantage than that afforded by the hanging drop, Hill devised the following procedure: Melted nutrient agar is poured into a Petri dish to a depth of about one-eighth to one-quarter inch. When cool, a block of agar is cut out, about one-quarter to one-third inch square, and IJ '0. KM 003 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES \ of the thickness of the agar layer in the dish. The block is placed, under surface down, on a slide and Eroteeted from dust. A suspension of the growth to e examined is then made in sterile water or a bouillon culture is used. The suspension is spread over the upper surface of the block as if making an ordinary cover-slip preparation. The slide and block are then set aside in the incubator at 37° C. for five or ten minutes, to dry slightly. A clean sterile cover-slip is then placed on the inoculated surface of the block in close contact, avoiding large air bubbles. The slide is then removed from the under surface of the block, and the cover-slip is inverted so that the agar block is uppermost. With the aid of a platinum wire a drop or two of melted agar is run along each side of the agar block, to fill the angles between the sides of the block and the cover-slip. This seal hardens at once and prevents slipping of the block. The preparation is again placed in the incubator for five or ten minutes to dry the agar seal. Finally the preparation is inverted over a moist chamber or suitable well slide. The cover-slip is sealed in place with white wax or paraffin. Vaseline cannot be used because it softens at 37° C. The "hanging block," thus prepared, is examined on a warm stage or in the incubator-room. Transplantation of Colonies. — The entire object of making plate culture by any one of the several methods given is to obtain single isolated colonies; these can be transplanted to other media, and the organism present can then be studied in perfectly pure condition. The colony as indicated is pre- sumably derived from a single cell, and consequently is a pure culture. The transplantations or sub- cultures can be made to gelatin, agar, serum, bouillon, milk, etc. When the colonies are on a plate or in a Petri dish a straight wire is used. The plate is first carefully examined under the microscope, and a colony is selected which is clearly single. If possible it should be the only one in the field of the No. 3 or one-third inch objective. The farther apart the colonies are the less likely are they to intermingle. As originally directed, the colonies were touched under the microscope by a sterile platinum wire, and in this way a few of the bacteria were removed. Care had to be taken that the wire did not touch the objective or any other part of the gelatin. This operation of "fishing," as it is called, obviously requires considerable practice and care. An equally good procedure is to pick out the desired colony under the microscope. The tube of the microscope is then raised, and the point of the sterile wire is brought down so that it cuts the colony and nothing else. The tube is then again lowered and the site of the colony examined to make sure that nothing but the colony was touched. If such is the case the wire is then used for the subculture. Stab Cultures,. — A tube of solid gelatin is taken, the cotton plug is seized by the right little finger and removed. The mouth of the tube is then flamed, after which the wire, laden with the bacteria, is inserted and carefully passed down the center of the gelatin. The organisms are thus planted along the line of inoculation. The cotton plug is replaced and the tube is labelled and set aside. The form of the growth is then noted from day to day, also the presence of gas, liquefaction, pigment, etc. The characteristics of the stab cultures are of the very greatest importance in the identification of bacteria. If the gelatin is old and partially dried, the passage of the needle is likely to cause a split in the medium. This can be avoided by melting and resolidifying the gelatin. (See Plates' XI. and XII.) Streak Cultures. — These are also known as "smear cultures." The gelatin or agar tubes are melted and solidified in an inclined position. Similarly solidified blood serum is also used; so also are the potato tubes. The infected platinum wire is drawn along the 904 middle of the surface of the medium by making one single streak. The growth develops along the line of inoculation, and spreads in a more or less character- istic manner. (See Plates XI. and XII.) Flask Cultures. — Flat flasks may be used for the cultivation of bacteria en masse where the organisms are desired in large quantities. The flask possesses an advantage over the Petri dish in that it is much less likely to become contaminated from without. For this purpose the Kolle culture flask, or any similar flat flask with a smaller mouth, may be employed. To a properly plugged and sterilized'flask, sufficient fluid gelatin or agar medium is added to form a layer about a quarter of an inch in thickness over one side. It is again sterilized by steaming and the medium is allowed to solidify with the flask lying on its side. When solid the free surface of the medium may be inoculated with organisms in broth or salt solution suspension by spraying or brushing over with a Kruse's brush. After the growth has suffi- ciently developed, it is removed by being scraped off. A spatula, glass rod with angle at end, or similar instrument may be used for this purpose. Sterile broth or salt solution may be used to aid in washing the culture free. For the cultivation of bacteria on a large scale, Novy and Vaughan introduced large metallic tanks with tightly fitting covers. Liquid Cultures. — The tubes of sterile bouillon, milk, ™rum, etc., are inoculated by simply introducing some of the material from a colony by means of the sterile wire. The subcultures from tube to tube are made in the same way as just given. The drawn-out glass-tube pipettes and spatulas can be used to transfer the material from one tube to another or to flasks. Anaerobic Cvlti ration of Bacteria. — The methods just given are essentially aerobic, since there is free access of air. As is well known there are two classes of bacteria with reference to their oxygen requirements. The aero- bic bacteria live in the presence of air, while the anaerobic thrive only in the absence of oxygen. In order to cultivate the latter, special methods must, therefore, be employed which will supply the needed conditions. Numerous procedures have been de- vised for this purpose, and to give all of these would be beyond the scope of this article. It will be sufficient to indicate the principles which serve as a basis for these methods, and to describe those which are most widely used. 1. Exclusion of Oxygen. — This was accomplished by Pasteur in his early work by pouring a layer of oil upon the culture fluid. This served to ex- clude the air and allowed the bacteria to develop. Koch obtained anaerobic conditions by covering the surface of the gelatin plates witli a thin sheet of mica, have done the same with glass plates. The Liborius method of cultivation in deep layers falls under this head. It is simple and is constantly used. Ordinary stab cultures are made in the suitable media, preferably glucose agar. Another tube of agar is liquefied, cooled to about 50° C, and the contents of this are then poured on top of the stab culture. Care must be taken to flame the mouths of both tubes so as to avoid contamination. The upper layer of agar serves to keep out the air. The cultures can be prepared equally well by employ- Fig. 5S5.— Liborius Deep Stab Culture, showing Growth of the Tetauua Bacillus. Others Reference Handbook OF THE Medical Sciences. Plate XI. 14. 15. 16. 17. 18. 19. 20. Micrococcus Staphylococcus of Osteo- The same Staphylococcus Streptococcus Streptococcus Streptococcus Tetragenus. m gelatine. pyogenes pyogenes. of erysipelas. of Puerperal myelitis. albus. Fever. TEST-TUBE CULTURES. Reproduced from Huber & Becker's "Untersuchungs-Methoden " REFERENCE BANDBOOK OF Till-: MEDICAL SCIENCES Bacteriological Ti< hnloni- ing agar or gelatin tubes filled with the medium to a depth ol about two inches. It is well to place the tubes in boiling water for some time to drive off the absorbed oxygen, then solidify rapidly by chilling. Use a tightly fitting stopper in the tube to exclude the air. After the stab is made, the line of puncture etoscs up itself, and the growth then develops in the Lower pari of the tube, as shown in Fig. 585. Isolated colonies ean also be obtained by this method. The liquefied medium is inoculated and dilutions are made as for shake cultures. The tubes are then solidified, and if necessary an additional layer of medium is poured on top. When the colonics develop they can be reached according to the directions given under shake cultures. Another pro- cedure is to make Esmarch roll tubes and then fill the inside with gelatin or agar. The drawn-out glass-tube pipettes (Fig. 578) have been used by Koux for this same pur- pose. The liquefied medium is inoculated and drawn up into the pipette, which is then sealed above and below the contents. The colonies which develop can be reached by cutting the glass. A somewhat similar pro- cedure was devised by Wright. A short glass tube with constricted ends is used. Each end has a piece of rubber tubing attached. One of these is connected with a glass tube which projects through the cotton plug of the test- tube. The test-tube contains bouillon, and this contrivance is sterilized and inoculated. The bouillon is then drawn up into the con- stricted tube, which is sealed by simply push- ing down on the tube, so that both rubber ends are bent back on themselves. 2. Displacement of Air. — This is accom- plished by passing through the tube or a suit- able container an inert gas till all the air has been displaced. Hydrogen is the least injur- ious gas for this purpose. It can be generated from zinc and sulphuric acid in a Kipp's gen- erator. The gas should be washed by passing successively through alkaline lead acetate, six per cent, potassium permanganate, and finally through a solution of silver nitrate. After passing through the apparatus the gas is sent through a small wash bottle which serves as a valve to prevent air from entering when the current slows up. Such a wash bottle is shown in Fig. 5S7, //. After the gas has passed for an hour or more it should be tested by ap- plying a light as it leaves the wash bottle. If the flame burns with explosions it is evident that all the air has not been displaced. The operation is continued until the gas burns evenly at the mouth of the tube. Owing to the danger of explosion the light should never be applied to the outflowing gas without the safeguard of the water valve for the pui po e oi obtaining plat e cull ires. Kita employed a flal bottle, Inning a tube fused al the lower end. The dilutions were mad.- in the ordinary tubes, after which the material was poured into these Basks, which were connected in series and hydrogen passed through. Finally the ends ■ -inled by fusing in the flame, while the neck of each flask was closed with a clam lied rubber I ill, e. Several modifications Of this bottle have been made, but they are linle used, since methods were soon per- fected whereby it was possible to make Petri plates in hydrogen. One 01 the earliest attempts in this direction was thai of Blucher, who made use of a funnel which was weighted with lead and inverted over the plates in a larger dish. Air was excluded by means of glycerin water. Hesse inverted a glass vessel in a circular trough filled with irv. Liborius used a copper bell- jar which was com- pn I 1 against a rubber gasket by means of set-screws; others made use of bell-jars in- verted upon a ground-glass surface. In many respects the Botkin apparatus is useful. It is shown in 1 ig. 587. It consists of a metal rack on which are placed the Petri dishes. This is set in a large outer dish which contains about. an inch of liquid petrolatum. A bell-jar is inverted over the stand. The inflow and out- flow tubes are of rubber stiffened by a copper wire on the inside. After the hydrogen has been passed for a sufficient length of time, the tubes are withdrawn and the apparatus is then set aside. The Novy apparatus shown in Fig. 588 leaves little to be desired. The hollow stop- per has two perforations, one of which is con- nected with a glass tube which extends almost to the bottom of the bottle. In the case of the plate apparatus the tube may be continued by means of a piece of rubber tubing. A perfect seal is obtained by simply turning the stopper through an angle of 90°. The bottle (Fig. 588, A) is made in two sizes, 8X16 and 10X20 centimeters, which dimensions do not include the neck. A piece of cotton should be placed on the bottom. The ordinary test-tubes containing any medium are inoculated in the usual way. The cotton plug is then cut off square, and by means of a pair of crucible tongs the tube is lowered into the bottle. It is advisable, if the cotton plug is very tight, to loosen it up by partially pulling it out. A single jar ean be filled in this way with a large number of tubes containing either solid or liquid media. The stopper is then put in place and the ap- paratus connected with a hydrogen generator. When the gas has passed for a sufficient length of time the bottle is closed by giving the stopper a turn. As will be seen, this jar can Fig. 586. — Fraen- One of the earliest attempts at making tube kel's Modification of cultures by this method was that of Liborius. the Liborius Tube be used likewise for the pyrogallate method. He made use of a special test-tube with a deli v- for Anaerobes. The plate apparatus shown in Fig. 5SS, B, ery tube fused into the side. After inoculation consists of two parts. The inner dimensions of the liquid medium, gas was passed through, and of the lower part are 12X12 centimeters. The Petri finally the neck of the test-tube, as well as the end of the delivery tube, was sealed in the flame. This method is of only very limited application, and re- quires much time and is expensive. Fraenkel's modi- fication is a distinct improvement. Ordinary large test-tubes are used. These are provided with rubber stoppers and delivery tubes, as shown in Fig. 586. After the inoculation of the medium and expulsion of the air, the tubes are sealed in the flame. If it is desired to obtain colonies, the tube can be converted into an Esmarch roll tube. This principle has been adapted in various ways plates are stacked into this compartment. The flanges are covered with a mixture of beeswax and olive oil (1:4). The two parts are then brought together and a rubber band is slipped over the outer edge of the flanges. Two or three clamps or small vises are now applied. The jaws of these should be covered with a piece of rubber tubing. Gas is passed as in case of the bottle, and at the conclusion of this operation the stopcock is given a turn so as to seal the apparatus. The other modification (Fig. 5SS, C) has a special stopper, which enables it to be used for vacuum 905 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES cultures. It can, however, be employed equally well for hydrogen cultivation. Moreover, both forms of the plate apparatus, as well as the bottle, can be used for the pyrogallate method. 3. Absorption of Oxygi n. — The most convenient ab- sorbent for this purpose is an alkaline solution of pyrogallic arid. The principle was first utilized by Buchner for tube cultures, as shown in Fig. 589. The large outer tube is provided with a closely fitting rubber stopper. On the bottom of the tube is placed about a gram of pyro- gallic acid and a suit- able support. The tube containing the nutrient medium is in- oculated in the usual way and placed on this support. Finally 10 c.c. of a ten-per-cent. solution of potassium or sodium hydrate are added from a pipette, as rapidly as possible, and the tube is then quickly closed with the stopper. As mentioned above, the Novy apparatus can be employed for the pvrogallate method. In the case of the jar a wide "tube is introduced which contains about two grams of the acid. After the culture tubes have all been inserted, about 20 c.c. of a twenty-five-per-cent. solution of sodium hydrate are introduced into the pyrogallate tube from a pipette, and the stopcock is then inserted as quickly as possible and turned. In the case of the plate apparatus a crystallizing-dish, about ten centimeters in diameter and about two centimeters high, is placed on the bottom, and about four grams of Fig. 5S7. — Botkin's Apparatus for Plate Cultures of Anaerobes. quired which fit one into the other like the halves of a Petri dish. They should be about two and one-half centimeters in height and with relative diameters such that when put together a space of one-half centimeter exists between the sides; the maximum diameter should be about ten centimeters for convenience in handling, although any other size may be used. After sterilization of the dishes the inoculated agar is poured into the smaller, the same as in ordinary Petri-dish plating, and again covered with the larger dish. The apparatus is in- verted when the agar is hard, the smaller dish is lifted out of the larger, and placed on a moist surface to pre- vent contamination. About three grams of pyrogallic acid are placed in the bottom of the larger dish, which stands open. The smaller dish, still in- verted, is placed into this, and sufficient five- per-cent. solution of sodium hydrate is added (between the sides) to fill the dish about one-half full. At once, liquid paraffin is run into the space between the si can bo placed on (lie side of I he concnv e slide. After the cover is in place the slide can be tilted so as to bring the two liquids together. A special slide for this purpose was devised by Braatz (Fig' 590). The hanging drop is made and placed over Hi' 1 well. The Hat. flask contains the pyrogallio acid ami communicates with the space below the drop. Strong alkali is finally added and the flask is closed with a stopper. 1'yrogallic acid can also be employed in con- nection with Hill's "hanging-block" culture. Another apparatus lor anaer- obic hanging drops is that of kuhne. It is very serviceable and can be used for either the gas or pyrogallic process. 4. Exhaustion of .1"'. —Pasteur em- ployed U-shaped tubes, from which the air was removed by means of an air pump. Gruber applied the princi- ple to the tube culture. He uesd a stout glass tube, which was provided with a stopper, through which passed a short glass tube by which connection was made with the air pump. The test-tube was constricted just below the stopper so as to facilitate the sub- sequent sealing process. The tube was filled in the usual way with the nutrient medium and inoculated. It was then connected with the pump, and as soon as the air was exhausted the tube was sealed at the constriction. The plate apparatus shown in Fig. 588, C, is in- tended for vacuum as well as gas or pyrogallate cultures. It can be used for tube or plate cultures. 5. Mixed Cultures. — This method of cultivating anaerobic bacteria corre- sponds to the way in which these organisms grow in nature. If the anaerobic is planted together with an aerobic, the latter will consume all the oxygen in the immediate neighbor- hood, and as a result the anaerobe will grow. Thus, if tetanus and hay bacilli are planted at the same time into a tube of bouillon, they will both develop. Other aerobic bacteria, such as Bacillus prodigiosus and Proteus vulgaris, can be used for the same purpose. The mixed culture method is also applicable to the cultivation of certain protozoa (amebas). But per- haps this is due to altered medium rather than any oxygen requirement. Musgrave and Clegg found that amebas could be cultivated upon a special medium when grown with pure cultures of certain intestinal organ- isms, as B. coli. 6. Cultivation in Air. — This of course is apparent rather than real. If a tube of glucose gelatin, prefer- ably colored with litmus, be inoculated with an anae- robe and then set aside in the incubator, an abundant growth will develop (Novy's method). Similarly, when deep stab cultures are made of the anaerobes, it will be found quite frequently that the water of condensation on the top of the medium is cloudy from the growth of the germs. The explanation in the one case is that air is excluded partly by the viscosity of the liquid and partly by the evolved gases. The gas formation accounts for the growth of the germs in the water of condensation. The culture in glucose litmus gelatin is by far the simplest way of growing anaerobes. Moreover, the cultures thus obtained retain their vitality for many years. In some cases the author has recovered cultures from tubes five and six years old. Collodium Sacs. — This method of cultivating has been used extensively by the Pasteur School for exalt- A Fig. 5 8 9.— Buchner's Pyro- gallate Method. ing the virulence of bacteria. The underlying Idea is to grow the organisms in the peritoneal cavity of an animal, and under such condition-, that the v. a te products of the germs will be removed, an abundant upply of nutrient material furni hed, and the germs themselves protected again t the action of phago- cytes. This is accomplished b i g the bacteria in an hermetically sealed sac, the walls of which are permeable to the waste products of the germ and to the soluble proteins of the peritoneal fluid. Several Russian workers have employed for this purpose the inner lining membrane of reeds, bul the best procedure is to make the sacs of collodium. Various methods have been devised for the rolling of the sac, but un- doubtedly the best and simplest, is that preferred in \.e j ' . laboratory by < iorsline, The rolling tube employed for making sacs is about twelve to fifteen inches long, and of any width that may be desired. For ordinary purpo e awidthof half an inch is sufficient. One end of this tube IS rounded off like a test -I ube, and has a two-millimeter opining at the tip. This opening is first closed with collodium cither by touching it with the cork which has been '"..red with the solution, or the collodium may be applied with the finger. Care must be taken to see to it that the collodium does not ^ei inside of the tube. In a few se ids the layer is dry enough 1 < > go ahead. The collodium used is the United Slate.-- Pharmaco- poeia solution, which by exposure to the air has I concentrated by one-third or one-half. It should be perfectly clear, and if not it must be filtered through cotton by the aid of a pump. The collodium can be kept in a glass-stoppered cylindrical vessel, such as is used for the collection of blood. The collodium is in- clined till it comes within a few inches of the opening. The rolling tube, with the opening freshly closed, is dipped in the collodium and rolled several times in the liquid. It may be rolled so that only the lower side of the tube touches the collodium. If the sac is to be very thin it is sufficient to roll the tube but Fin. 500. — Braatz'.s Slide for Anaerobic Hanging-drop Examinations. two or three times, after which it is raised from the liquid and rolled in the ether atmosphere in a hori- zontal position till the collodium has set. If the layer is not thick enough the tube can be returned to the collodium, but care must be taken to avoid the forma- tion of air bubbles. The coated tube is finally rolled in the air until it has reached the proper consistence. This can be ascertained by touching the thickest part with the finger. The collodium layer should be rather firm. The tube is then immersed in distilled water for a minute or two. If the collodium is not suffi- ciently hard, it wall cloud or become milky on contact with the water. It should remain perfect ly clear, and when finished a thin sac placed in water is almost invisible. To detach the sac the tube is filled with distilled water, and by blowing into the open end the water can be forced through the opening below and upward between the sac and the tube. By slight manipula- tion with the fingers the detachment can be effected readily on all sides. The free end is then trimmed square, after which the sac is placed in distilled water, where it remains until it is ready to be attached to the glass tube. An ordinary test-tube having a diameter slightly less than the sac is constricted in the blast flame at about two inches from the end. A scratch is then 907 Bacterio.ogical Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES made, about half an inch below the constriction, with a diamond, and with the aid of a hot rod the end is removed. The resulting tube has the form shown in Fig. 591, a. The cut end should be rounded in the flame so as to remove the sharp edge. The inside of the neck of the sac is dried by means of filter paper, after which the end of the tube is inserted. This can be done more easily if the end of the tube is previously dipped in alcohol. The next step, that of shrinking the sac upon the tube, is very important and requires care. Most of the shrinking is done by rotating the tube, in a horizontal position, some distance above a small spare-flame burner. In this way the collodium can be made to contract down Fig. 591. — Preparation of Collodion Sacs. (Xovy.) upon the glass, but the operation must be done slowly and at some distance above the flame, otherwise there is danger of igniting the sac. The adhesion is rendered more complete by the application of a hot glass rod. Finally a silk thread is wound as closely as possible over the glass neck, and this in turn is covered with a layer of collodium. The sac now lias the appearance shown in Fig. 591, b. The finished sac is now filled with distilled water and placed in a test-tube on foot, which also contains water (Fig. 591, e), and the whole is sterilized by steaming in an autoclave for half an hour at 110° C. When the sac is to be used, the water is removed from the inside by means of a drawn-out pipette and replaced in like manner with bouillon which has been inoculated with the organism to be tested. The threaded part is then wrapped in a piece of sterile filter paper, for convenience in handling, and the con- striction is sealed in a sharp-pointed flame. The sealed sac is then placed in a sterile test glass. The rabbit or guinea-pig which is to receive the sac is now attached to a holder and the hair is removed from the abdomen. The field of the operation is thor- oughly washed with lysol or mercuric chloride. After the animal is anesthetized an incision is made in the abdominal wall, and through this the sac is in- troduced into the peritoneal cavity. The incision is then sewed up and covered with cotton and a little collodium. The sac is allowed to remain in the animal for a few or even for several months. To remove it the annual is killed with gas. The sac is freed from the adhesions and transferred to a sterile test glass with the glass end downward. By means of a hot rod an opening is burned into the end of the sac, and through (llis ll " - contents arc removed by means of a drawn- out tube pipette. When large sacs are to be inserted mi 'i an animal it is advisable to strengthen them by 908 placing within a perforated glass tube as shown in Fig. 591, d, e. The collodium sacs can be used not only as just de- scribed, but also with marked advantage for dialyzing experiments. For this purpose the sacs can be made an inch or more in diameter and twelve or fifteen inches long. The thin collodium membrane is con- siderably more permeable than parchment paper Separation of Spore-forming from N on-spore-forming Organisms by Heal.— Heat is sometimes employed in the separation of spore-forming from non-sporelform- mg species of bacteria when both are present in mixed '•iilture. For this purpose the mixed culture con- taining spores, is heated for fifteen minutes at ,so° C. The vegetative forms are destroyed while the heat-resisting spores remain viable and will develop under proper conditions. If more than one species of spore-forming organisms are present, they may lie separated further by the plating method, or by animal inoculation. Mechanical Separation of Bacteria from Fluids. — For this purpose various types of the centrifuge are used. It is essential that they run smoothy, and revolve at a high speed. The type best adapted for the separation of bacterial and other cells from fluids, pathological exudates, etc., are those equipped with slender glass tubes with conical ends to collect the sedimenting material. They are usually driven by means of water or electric motors. The electric- motor type is more satisfactory and may be procured to be driven by cells, storage battery, direct or alternating current. The ordinary clinical centri- fuge driven by hand may be used, but in most cases this is exceedingly slow in sedimenting organisms. Drying of Bacteria, Toxins, Antitoxins, etc. — In the chemical or biological study of bacteria and their prod- ucts, it frequently becomes necessary to remove the water content. Since the labile constituents would be destroyed if dried by heat, as in ordinary chemical manipulations, other means must be used. This can best be done by drying in vacuo in the presence of certain substances, as phosphoric anhydride (P„0 5 ) or concentrated sulphuric acid (H 2 S0 4 ) which readily absorbs the water vapor. The temperature may be kept at that of the working-room or even lower. Most suitable for this purpose is the ordinary heavy glass vacuum desiccator. This is partially divided, with an upper and lower chamber, by means of a movable perforated porcelain plate which forms a shelf for receptacles. Either in the wall or cover of the desiccator a heavy glass tube with cock is fused or passed by means of a ground-glass stopper. This forms a means of communication with the interior of the vessel. The apparatus must be of heavy con- struction to prevent breakage from the external air pressure when air content is exhausted. For use, first place in the bottom chamber a layer of con- centrated sulphuric acid, or, better, phosphoric an- hydride, filling the chamber about one-quarter to one- half full. The material for drying should be previously spread or poured in a flat dish, such as the halves of a Petri dish. Now place the dish on the porcelain shelf over the water-absorbing substance. Adjust the cover and firmly seal in position with an adhe- sive paste. It is well also to use the same paste on the glass stopcock to prevent leakage at that point. Such a paste may be prepared by taking one part of pure rubber (black elastic rubber tubing cut in small pieces), one part of paraffin, and three parts of vase- line. Mix together and heat until dissolved. Take extra thick-walled rubber tubing and connect an air pump (of the large type) to the exhaustion tube of the desiccator. Open the glass stopcock and pump out the air to produce vacuum. At once close the glass stopcock of desiccator tube, and observe if any air leaks are evident. If not, detach pump. It is necessary to pump out the desiccator at least once a day until the substance is entirely dry. The ordinary i;i;ii:i:i:nci: handbook ok tiik mkdkal scikxces Bacteriological Technique water pump cannot be used owing to the water vapor which is always present and travels back during exhaustion. The alici\ e ni. 'I hod fur I he de iccal ion of main ia] is open to certain objections. Among these may be mentioned: the time period required in reducing any considerable volume of immune serum, toxic broth, etc., to the dry state; the changes resulting in blood serum during the process which makes re-solution difficult in most instances; and, in the case of labile Fig. 592. — Syringe Holder and Sterilizing Pan. (Novy.) components, as toxins, complement, etc., a great depreciation, or even a total loss of value may result. A method of drying, proposed by Shackell, offers, at least, a partial solution of the above difficulties. By his method, which has been further improved by Harris, the material to be dried is thoroughly frozen as rapidly as possible by means of a salt-ice mixture, or by means of carbon dioxide snow. The frozen sub- stance, in an open dish, is at once placed in the bottom of a Scheibler's vacuum jar (which has also been thoroughly chilled, by being partially immersed in a salt-ice mixture), then an open dish containing con- centrated sulphuric acid (cold) is placed upon a wire gauze support in the upper portion of the jar. The jar is sealed at once with the exception of a connec- tion which is made with a Geryk vacuum pump. The pump is put in operation immediately to exhaust the air from the vacuum jar. When this is accomplished in so far as possible, the connection is cut off by means of the stop-cock. Care must be taken to exclude all air leaks, which is not difficult if a proper lubricant is used. Occasionally the vacuum jar is rotated gently in order that the sulphuric acid may be kept well mixed, and its absorption ability kept at its highest degree of efficiency. By this method, Harris found that even a rabbit brain (rabic) would become thoroughly dry in from thirty-six to forty-eight hours. Desiccated serum readily passed into solu- tion after this means of treatment. Care should be taken to seal the materials, when finished, to exclude the air since the dried material is quite hygroscopic. Inoculation of Animals. — According to the nature of the experiment these are made with pure or impure cultures of bacteria, or with the chemical products elaborated by them. The use of impure material is met with in diagnostic work. Thus in suspected glanders the discharge is introduced into animals in order to ascertain if the bacillus of glanders is present. The same is often done in tuberculosis, pneumonia, bubonic plague, anthrax, tetanus, rabies, etc. In all these experiments the animal serves as a plate, since it eliminates all the saprophytic bacteria which may be present in the original material and allows the disease-producing ones to develop in pure or almost pure cultures. The inoculation with pure cultures is made to test their identity, to study their effect upon animals, to ascertain the diverse means of infection, and for purposes of immunization. The inoculation with the chemical products enables one to ascertain t be pre cue, oi poi onous substam produce vaccines or antito The inoculations may be made with a fine need! lance, I ii 1 1 i e ott en with the aid ol a syringe. The drawn-out glass-tube pipette is also used a .. introducing infectious material. The syringe used varies with different workers. The Germans are especially favorable to the Koch svringe, which consists of a glass cylinder, graduated, tin row end of which connects with the i die whili upper end tits into the metal collar of a rubber bulb. The advantage claimed is thai the cylinder and Deedle can be effectively sterilized by dry heat. As a mat ter of fact the Koch syringe is extremely inconveni and unsatisfactory, and equally good results with less time and annoyance are obtainable with the ordinary hypodermic. The all-glass type of hypodermic syringe is perhaps the i satisfactory for inoculation purposes. The latter models, of course, must be sterilized by boiling in water for ten or fifteen minutes. A convenient holder for the syringe is shown in Fig. 592. When large quantities of liquids are to be introduced, as when injecting horses with diphtheria toxin in the preparation of antitoxin, an apparatus similar to that shown in Fig. 593 can be used. The necessary instruments, such as knives, scissors, needles, etc., are sterilized by boiling in water, or better in a saturated solution of borax. A very con- venient sterilizer for this purpose is that shown in Fig. 598. In all operations the animal must be secured in some way or another. Various kinds of holders have been constructed for this purpose. That of Latapie, shown in Fig. 594, is very convenient, and is to be preferred to the ordinary models. It can be used for guinea-pigs, rabbits, birds, etc. The Voges holder, shown in Fig. 595, is useful for taking temperatures and for injecting small animals. A good substitute can be made by using a glass cylinder. Special holders have been devised for rats and mice. These, however, can be handled best by means of a pair of compression or artery forceps. The animal is seized by the nape of the neck with the forceps, which is then transferred to the left hand. The tail and the hind legs are also held by this hand. Fig. 593. — Graduated Cylinder for Injecting Liquids. (Novy.) The animal in this way is put upon the stretch, and the inoculation can then be made with the right hand. Even full-grown wild rats can be handled in this way without the help of an assistant. After inoculation the animals are placed in special jars or cages. The ordinary glass battery jars, pro- vided with a galvanized-wire top; weighted with lead, serve to confine rats and mice, and can even be used for guinea-pigs (Fig. 59G). If the animals are 900 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES inoculated with a very dangerous organism, such as the pest bacillus, it is advisable to place the jar inside of a ten-gallon crock. In special cases, as in animals infected with trypanosomes, bubonic plague, etc., it is well to cover the cage with a piece of mos- quito nrtting or cheese-cloth as a safeguard against insects spreading the infection. Guinea-pigs, rabbits, and the like can be kept in the Vaughan cage shown in Fig. 597. The cage proper is thirty centimeters high, thirty-eight centimeters deep, and fifty-four centimeters wide. The feet are twelve centimeters high. Fig. 594. — Latapie's Animal Holder. (Novy.) 1. Cutaneous Application. — Ordinarily bacteria do not penetrate the unbroken skin or mucous mem- brane, but the direct application of some organisms, even in the absence of any known lesion, leads to infection. This is the case when the virus of the foot-and-mouth disease or the bacillus of plague is brought into contact with the mucous membrane. The pus germs, when rubbed into the skin by the aid of vaseline, may cause infection. 2. Subcutaneous Application. — For this purpose the hair is removed from the region where the inocula- tion is to be made. The place is then rubbed with a disinfectant. In the rat this is usually on the back, at the root of the tail; in the guinea-pig it is on the side. A nick is made with sterile scissors, and then with a narrow scalpel or spatula a pocket is made Fig. 595.- Hulder for Small A n i m als. (Novy.) under the skin. A piece of tissue, a bit of earth, blood-laden wire, etc., is then introduced into the opening, which if made small requires no special closure. 3. Subcutaneous Injection. — The suspended material is introduced under the skin by means of a syringe. The hair should first be clipped close and the place of inoculation touched up with a disinfectant. 4. Intravenous Injection. — In the case of the rabbit this is easily done. The marginal branch of the posterior auricular vein is selected, although it may appear to be narrower than the needle. The hair may be removed and the surface of the ear rubbed freely to stimulate circulation. A clamp is then applied at the base of the ear so as to distend the vein. The needle is then inserted at a very slight angle to the vein. In other animals the jugular can be exposed and the injection made without any difficulty. 5. Intraperitoneal Injection. — This procedure is very commonly resorted to. The skin over the abdomen should be raised and the needle of the syringe is then introduced into the cavity. Care should be exercised in order not to penetrate the hollow viscera in small animals. In such case the fluid may enter the intestine, for example, and be discharged without producing any effect. In the case of the horse, while the animal is standing a trocar is introduced through the skin at a point a few inches anterior to the crest of the ilium. 6. Intrapleural Injection. — The needle is introduced into the right pleural cav- ity, care being taken to prevent any injury to the lung or to the heart. Large amounts of liquid can- not be tolerated by the animal. 7. Intracranial Injection. — This method was intro- duced by Pasteur as a means of surely infecting animals with rabies. The procedure is followed out when inoculating animals either for diagnosis or for the purpose of preparing the vaccine for hydropho- bia. It is usually practised on rabbits and guinea- pigs. The skin from between the ears forward is shaven clean and disinfected. An incision about an inch long is then made. Those of the Pasteur school apply a hand trephine, and make an opening into the skull. A small trephine, operated by a dental engine, Tig. 596.— Rat Cage and Forceps. Fig. 597. — Vaughan Cage. (Novy.) is much more convenient. In the absence of either an opening may be made into the skull with a stout scalpel. By means of a hypodermic syringe a few drops of the brain or cord suspension are then intro- duced under the dura. At times the injection is made into the brain proper, in which case it is spoken of as intracerebral. After the injection a suture or l wo are applied, and the wound is covered with collo- dium and cotton. 910 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES narlrrliiloKlcal lYrlinlquo 8. Intraocular Injection. — Cocaine is first applied to the eye, after which this is fixed with forceps and tilt' material is injected into the anterior chamber. ]f desired, an opening can be made with a cataract knife or narrow scalpel and the solid material can be introduced in this way. 9. Injection into the Lymphatics. — This is usually made by introducing the material into the testicles. 10. Respiratory Infection. — While the preceding methods may be looked upon as wound inoculations, this concerns itself as nearly as possible with duplicat- ing the natural infections along the respiratory tract' The direct method consists in causing the animal to inhale the finely divided material, w hich can be readily done by means of an atomizer. In some cases I he animal is caused to inhale irritating fumes, such a bromine vapor. This excites a slight inflammatory reaction of the respiratory mucosa, and causes the animal to become more liable to infection. When the atomizer is used to produce a spray, the operator must take special precaution to protect him- self against infection. The animal should be placed in a specially constructed tight box. All openings for air should be loosely packed with absorbent cotton which acts as an air filter. The spray can be throw n in through an opening admitting the tube of the atomizer with sufficient cotton wool about it to pre- vent escape of spray from the aperture. Another procedure may be called the intratracheal injection. This is carried out by making an opening into the trachea, and through this introducing the infectious agent. 11. Alimentary Infection. — Since water and food serve to introduce the pathogenic agent of many diseases into man and animals, it is necessary at times to resort to a similar method of infection. The animal may receive the infectious agent in water. milk, or in solid food. Thus bread may be soaked in a bouillon culture of the organism. At other times it may be necessary to introduce the material into the stomach by means of a rubber tube. In order to prevent the animal from biting the tube. it is well to pass it through a perforated cork or plug of soft wood. Under exceptional conditions a lapa- rotomy may be made and the material injected into the intestines. This is spoken of as the intraduodenal injection. Observation and Autopsy of Injected Animals. — The matter of suitable caging of animals has already been touched upon. Attention may be called to the need of daily observations of the infected animals, so as to note the symptoms manifested. The animals must have plenty of food and drink, and must be kept in as clean a condition as possible. Their weight and temperature should be taken daily, for in this way the best information can be gained as to the physical condition of the animals. When the animal dies it should be autopsied at once, or else it must be put aside in an ice-box. The need of immediate examination is shown in some of the trypanosomatic infections, as nagana and caderas, where the organisms may disappear from the blood within an hour or so after death. Moreover, delayed examination may lead to the invasion of the organs of the cadaver by the intestinal bacteria, in which case the search for the specific germ is rendered more difficult, if not impossible. The animal is prepared for autopsy by being placed on its back and tacked down on a board. A conven- ient board of this kind is one which is about thirty- four by fifty-four centimeters and has a raised border. The cracks, if any, should be filled with paraffin. After the animal is laid out , the hair should be thor- oughly moistened with mercuric-chloride solution. The necessary instruments can be sterilized in a copper sterilizer, such as is shown in Fig. 598. In the absence of such an arrangement the instruments may be sterilized by heating directly in the flame, but this, of course, injures them. A searing iron, several drawn-out pipettes, and sterile dishes, as well as the necessary media, should be conveniently at hand. Willi a sterile scalpel an incision is made along the entire length of the body from the neck to the pubis. Lateral incisions are then made in the direction of each of the extremities, and the two large flaps thus resulting are t urned back. The condition of the sub- cutaneous tissue, the presence Of edema, bloody ■ ■I! ii ions, enlarged lymphatic glands, etc., are noted. The glands or portions of the ti ue maj be trans- ferred by means of sterile instru nts to a sterile dish. Cover-glass smears or streaks can be made and examined eil her at once or later. The abdominal and thoracic cavities are usually opened at the same time. 'I lie abdominal wall in the lower part of the body is slightly rai ed and nicked with Sterile scissors; then the lower blade is inserted and the incision prolonged upward to the pit:. 598. — Iustruiueut Sterilizer. diaphragm. The ribs are then cut as low down as possible, and the wedge-shaped piece of the wall of the thorax is removed. The condition of both cavi- ties and of the organs is carefully noted. Cover- glass streaks are made from the peritoneal surfaces and from the cut surfaces of the organs, and examined either at once or later. Any fluid which is present in the cavities may be transferred to sterile tubes by means of the pipette. Cultures should always be made from an intact organ. For this purpose it is cut open with sterile scissors, and a piece of the pulp removed on a sterile wire or by the aid of a Nuttall spear or spatula (Fig. 577). The heart blood is usually given preference for culture purposes. The pericardium should be opened, after which the surface of the heart is seared with a hot iron. An incision is then made into the ventricle, from which the blood can be removed by the aid of a looped wire. The best way of removing the heart blood is by means of a sterile Pasteur bulb pipette. The end of this is broken, flamed, and when cool it is inserted into the heart, and by suction the blood is drawn up into the pipette. The contents of the tube can then be used to inoculate culture media or for making blood streaks. After the autopsy the animal should be placed in a vessel and steamed or autoclaved, and eventually burned. The board should be washed with mercuric chloride, and all instruments and utensils should be sterilized by steaming. Throughout the autopsy care must be taken to prevent infection either by the scattering of material on the floor or by its being carried away by insects. Examination of Bacteria. — In order to gain some definite information regarding the bacteria which develop on the nutrient media or in the ani- mal body, recourse must be had to the microscope. 911 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES The organisms may be examined in the living con- dition or in stained preparations. The former pro- cedure is resorted to so as to learn all that is possible regarding the living cell: its form, size, color, granula- tions if any, motion, grouping of the cells, presence of spores, etc. Such facts are ascertained by making a preparation in which the bacteria will continue to live for some time. Living Bacteria. — 1. The simplest procedure is to place a drop of the bacterial liquid on a slide, after which the cover-glass can be applied and the prepara- FlG. 5U9. tion examined under the microscope. This method is usefiii for rapid orientation, but it has certain draw- backs, chief among which is the fact that evaporation takes place along the edge of the glass, and as a result currents are established in the liquid. Such currents tend to interfere with the observation of any one organism or group of cells. Again, a prepa- ration of this kind cannot be kept under observation for any length of time on account of the desiccation which soon takes place. 2. The examination in a hanging drop, as it is called, obviates the difficulties mentioned. A rather thick slide with a concave well is used (Fig. 599). A ring of vaseline is spread around the edge of this well. A clean cover-glass, about three-fourths of an inch in diameter, is placed on the table, and a drop of water is applied to the middle by means of a looped platinum wire. It is desirable that the drop should spread out flat, and if it does not it is because the cover-glass is not clean. The drop of water is then inocuiated with a little of the culture. Just enough material is added so that, the liquid is slightly cloudy. The vaseline-ringed slide is then inverted and brought down upon the cover-glass. The preparation is turned over, and, if need be, pressure is applied to the border of the glass so as to have an air-tight hang ing drop. Under these conditions evaporation does not take place, and consequently the specimen may be examined for hours, if necessary, without any inter- ference by currents due to evaporation. As men- tioned above, this method can be used for the cultiva- tion of bacteria, and thus their growth and multi- plication can be followed out. In that case it is necessary to use a flamed cover-glass and a sterile liquid. Instead of the concave slide a so-called well-slide can be used (Fig. 000). This is essentially a square bit of glass with a circular opening, which is cemented to an ordinary glass slide, and the hanging drop is then made in the manner described. One disadvantage in either method lies in the fact that the drop is more or less convex, and consequently when using higher powers it is difficult to examine the deeper portions. This difficulty can be overcome by employing the Ranvier slide, which has a circular trough, Mud the portion within the circle is ground down so thai its level is about 0.1 mm. below that of I lie slide, When a drop of liquid is placed within the circle and covered with a cover-glass, the liquid 912 o. c -Concave Slide showing Hanging Drop. A, Surface view; B, side view. spreads out into a thin layer, every part of which can be examined under the microscope. A ring of vaseline is placed along the edge so as to prevent evaporation. By flaming the slide and cover-slip, and using sterile liquid the preparation can be ob- served for several days if need be. This method is especially to be recommended for studying trypano- somes, malaria parasites, etc. Staining of Bacteria. — In order to obtain good stains it is necessary to have good clean cover-glasses. The cover-slips, as purchased in the market, are unfit, for use until they have been cleaned. One method of doing this is to heat the slips in a beaker with concentrated sulphuric acid and potassium bichromate. The cover-glasses are then washed in running water, after which they are kept in alcohol. Another procedure which gives very satisfactory results is to soak the cover-glasses first in alcohol, after which they are wiped with soft, washed linen, placed in an Esmarch dish and heated in a dry-heat sterilizer at about 200° C. for an hour or two. This high heat completely destroys ■ the organic matter that may be on the glasses. A" cover-glass is not clean if a small drop of water, when spread over the surface, does not remain even, but gathers into droplets. Several kinds of forceps have been devised for holding cover-glasses while staining. The Cornet forceps (Fig. 601, a) is well known, and is useful though rather awkward. Stewart's modification is widely used (Fig. 601, b). A much more convenient type of forceps is shown in Fig. 601, c. The lower blade has a thin edge which permits one to pick up the cover-glass without contact with the fingers. The upper blade is bent in order to avoid capillarity, and is narrowed to a point so that the specimen is held by point contact. A catch serves to hold the cover-slip in place. Aniline Dyes. — The aniline dyes which are em- ployed for staining purposes are either basic or acid in character. The former contain amido groups and are spoken of as nuclear stains, since they color the nuclei of cells as well as bacteria. The latter contain hydroxyl groups and do not stain bacteria but are used chiefly for contrast coloring, and to some extent for decolorizing. The basic dyes are usually employed as salts of hydrochloric acid, while the acid dyes occur as sodium or potassium salts. A', .• 3 Fig. 600. — Cell Slide showing Hanging Drop. A, Surface view; B t side view; b, edge of cell; c, hollow of cell; d, cover glass; e f hanging drop. Among the basic aniline dyes which are commonly employed may be mentioned fuchsin, gentian violet, methyl violet, crystal violet, methylene blue, thionin, safranin, methyl green, neutral red, and vesuvin or Bismarck brown. These are all more or less crystal- line powders, and while some are definite chemical compounds, others are mixtures. For this reason various brands are met with on the market, and it will be readily understood why the exact duplica- tion of stains is not always possible. Reference Handbook OF THE Medical Sciences. Plate XII. 1. 2. 3. 4. 5 6 7 Bacillus of Bacillus ot The same Finkler-Prior's Deneciie's Miller's Bacillus iA' Tuberculosis. Cholera Asiat- ics. in gelatine. Comma Ba- cillus. Bacillus Bacillus Typhoid Fever 8. 9. 10. 11 12. 13. 14 Pneumococcus. Bacillus or Bacillus of The same Bacillus of Bacillus of Bacillus of Glanders. Anthrax. in gelatine Malignant Oedema Septicaemia of Mice Septicaemia of Rabbits 15. 16. Bacillus of Bacillus of Chicken Pigeon Cholera. Diphtheria n. Slide Culture (reduced? Plate Culture treducedJ TEST-TUBE CULTURES. Reproduced from Huber & Becker's "Untersuchungs-Methoden. REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique It is advisable to keep on hand not only ihe solid dyes, but also stock solutions which are saturated alcoholic solutions. The amount iv<|iiircd to .satu- rate will vary from two to live per cent. The concentrated alcoholic solutions are never used as such, luii serve for the preparation of the dilute dyes which are the stains proper. Tin; latter are made by placing a few cubic centimeters of the con- centrated dye in a small tincture bottle, and adding ten to twenty parts of water. This bottle is then provided with a cork and a piece of glass lulling which Fig. 601. — Cover-glass Forceps, a, Cornet's; 6, Stewart's; Novy's. serves as a pipette. The different dilute dyes can be kept in a stand, such as is shown in Fig. 602. The dilute dyes after a while undergo alteration and yield deposits. In that event they should be filtered before use, or else new dilutions should be made. The acid aniline dyes are represented by eosin, acid fuchsin, and fluorescein. The concentrated and the dilute dyes are prepared as above. The staining solutions may be used as such, or their properties may be accentuated by the addition of substances which act more or less directly as mordants. A number of these solutions are in daily use, and for that reason their preparation is here given. Loffler's methylene blue is made by adding 30 c.c. of concentrated methylene blue to 100 c.c. of a 0.01- per-cent. solution of potassium hydrate. A similar solution with less alkali was first used by Koch. The alkali not only serves to make the cell more permeable, but also increases the staining power by liberating the free base from the dye. Carbolic fuchsin, or Ziehl solution, is made by add- ing 1 gram of fuchsin and 10 c.c. of alcohol to 100 c.c. of a five-per-cent. carbolic-acid solution. The stain is very widely used for simple as well as double stain- ing. Czaplewski modified it by substituting glycerin for the alcohol. His solution is prepared by rubbing up in a mortar 1 gram of fuchsin with 5 grams of car- bolic acid, and to this 150 grams of glycerin and 100 c.c. of water are added. Carbolic methylene blue, first employed by Kiihne, consists of 1.5 grams of methylene blue, 10 grams of absolute alcohol, and 100 c.c. of a five-per-cent. solution of carbolic acid. Carbolic thionin consists of 10 parts of a saturated solution of thionin and 100 parts of a one-per-cent. solution of carbolic acid (Nicolle). Carbolic gentian violet is"made the same as the pre- ceding (Nicolle). Vol. I.— 58 Aniline Water, Gentian Violet, etc. The carbolic acid, like the alkali, favors the penetration ol the tain. Aniline water acts in like manner and was in i used by Ehrlich. To prepare the aniline water a few cubic centimeters of aniline are placed in a test- tube, and this ia then filled with distilled water and thoroughly shaken. The milky liquid i filtered through a moist lilt or. To the water-clear filtrate enough concentrated fuchsin or gentian violet D then added to make the Liquid opaque, and bo that it just begins to form on the surface a slight metallic film of precipitated dye. The solution is then used as such, but if the deposit is very marked it may be necessary first to filter it. The aniline-water dye do not keep very well, and for that reason it is well to make a fresh solution every time thai it is to be used. Oil of cloves has been suggested by London as a substit ule for aniline. The aniline-water stains were first, employed by Ehrlich for coloring the tubercle bacillus, and are still used for that, purpose, They are, however, employed especially for staining whips and in con- nection with drain's stain. In the latter case, after I lit; preparation litis been stained with the solution, a mordant is applied, known as Lugol's solution, which serves to form a difficultly soluble compound between the dye and the cell contents. Lugol's solution consists of 1 part of iodine, 2 parts of potassium iodide, and MOO parts of distilled water. The Staining of Cover-glass Preparations. — Thee may be considered under the head of (1) simple, -') double, and (3) special stains. For the simple stains, when it is desired to have a heavily colored prepara- tion, either fuchsin or gentian violet is used. When it is desired to bring out structural characteristics, it is advisable to employ solutions which stain more feebly, such as methylene blue or thionin. In either case the simple or reinforced stains, given above, may bo employed. To make a stained preparation of a pure culture the procedure is as follows: A drop of water, preferably distilled, is placed upon a clean cover-glass, which either lies on a board or is held in a pair of forceps. By means of a sterile platinum wire a minute amount of the bacterial growth is picked up and transferred to the water. Only enough should be added so as to impart to the water a slight cloudiness. The remain- der on the wire is then burned off. The drop is then spread over the whole surface of the glass and allowed Fig. 602. — .Stand for .Staining Solutions. to dry in the air, or the process may be hastened by passing it above a flame. Care must be taken not to dry too rapidly as, in such case, vacuolation of the protoplasmic contents of the cell results. The air- dried preparation must now be fixed in order that the bacteria may not be washed off in the subsequent treatment. The fixing is done by passing the cover- glass three times through a llame. Care must be taken not to scorch the specimen, for in that case the dye will not act. It is well to turn down the 913 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES flame so that it is at most but two inches high. The properly fixed cover-glass is now covered with the Main, which is allowed to act for ten to twenty seconds. The dye is then washed off under the tap and the cover-glass inverted upon a glass slide. Any water which ma3' be on the surface of the slip should be removed bj r means of a piece of filter paper. The preparation can now be examined under a No. 7 objective, or with the one-twelfth-inch oil immersion lens. If the specimen is such as to merit preserva- tion a drop or two of water may be applied to the edge, and in this way the slip can be floated off with- out damaging the film. The excess of water can then be touched off with a piece of filter paper, after which the specimen is dried in the air or by passing it over the flame. The thoroughly dried film is then inverted upon a drop of Canada balsam placed on the center of a clean slide. By gentle warming or by pressure the balsam can be made to spread out evenly. Smear or streak preparations made from the fluids or organs of the body are stained in the same way. In selecting a stain for such preparations perhaps Loffler's methylene blue solution is the most satis- factory. It does not stain the tissue material so deeply a- some of the other commonly used bacterial stains. Also Pappenheim's pyronin and methyl-green mix- ture may be used for the same purpose. It is com- posed of 3 to 4 parts of saturated aqueous solution of methyl-green to 1 to 1J parts of saturated solution of pyronin, and applied the same as the above stain. With this stain bacteria take a bright red coloration; the nuclei of the body cells take a bluish stain. The fixation of the cover-glass when it contains much pro- tein matter, as in the case of blood streaks, requires special care. The best results are obtained by im- mersing the slip for a few minutes in a mixture of equal parts of absolute alcohol and ether. Fixation is thus accomplished without any injury to the blood cells. It is sometimes advisable, instead of adding the dye to the cover-glass, to float the latter upon the dye in a watch-glass. To make good blood preparations requires consider- able care and experience. A small drop of blood is placed on a perfectly clean cover-glass, which is held in a pair of forceps. A second cover-slip is then applied evenly and without pressure, and as soon as the blood has spread out the two glasses are drawn apart. The blood cells must not be crushed and should lie in a single layer. The smears from the cut surface of an organ are made by gently applying the cover-glass, without pressure, and then drawing it away; or a piece of the organ may be taken up in the forceps and streaked over the cover-glass, care being taken to leave only the thinnest film possible. The ordinary dass slide is often used in place of the cover-glass. The streaks or blood smears are made as in the case of the latter. When the growth is hard, as in the case of actinomyces, it is well to crush it between two glass slides. Double Staining. — This procedure is resorted to when staining the tubercle bacillus and the allied acid-resisting bacilli. It is also used for staining spores, and in differentiating bacteria by means of Gram's stain. Other special methods are given under gonorrhea and meningitis. The group of acid-resisting bacilli, the type of which is the tubercle bacillus, is stained with more or less difficulty by the simple stains. The dye, however, can be forced into the cell by the aid of heat, and especially if the reinforced stains, such as carbolic fuchsin or aniline-water gentian violet, are used. On subsequent treatment with acid and alcohol the ordinary bacteria which chance to be present are readily decolorized, whereas the acid-resisting retain th -lain. A contrast color, such as methylene blue, will then stain the background and the ordinary bacteria a light blue. Staining of the Tubercle Bacillus. — The cover-glass is air-dried and fixed in the usual manner, after which any one of several methods may be used. The Ziekl-Neelsen method is usually employed. It is carried out as follows: The cover-glass, held in the forceps, is covered with carbolic fuchsin and heated over the flame so that vapors are given off for one or two minutes. It is then rinsed in water and dipped for a few seconds in a twenty-per-cent. solution of nitric acid, after which it is washed in dilute alcohol i sixty per cent.) till it is almost colorless. Methyl- ene blue is then applied for a few seconds and washed off. The specimen is transferred to a slide, the surface dried, and examined under the microscope. The tubercle bacilli will appear red on a blue back- ground. The ordinary bacteria will appear blue. The Koch-Ehrlich method consists in staining with aniline-water fuchsin or gentian violet with the aid of heat for a few minutes. The specimen is then decolored in thirty-five-per-cent. nitric acid for about a quarter of a minute, washed in dilute alcohol till nearly color- less, after which methylene blue or Bismarck brown is applied for a contrast color. In the Fraenkel-Gabbet method the preliminary staining is effected with carbolic fuchsin as above. The decoloration and contrasting is done at once by immersing the cover-glass in a saturated solution of methylene blue in the following: Sulphuric acid 25 parts, alcohol 50 parts, distilled water 1,000 parts. It is then rinsed with water and examined. Czaplewsky's method differs from the preceding in the way the decoloration is effected. He employed for this a solution of one gram of fluorescein and five grams of methylene blue in 100 c.c. of alcohol. The specimen is first stained with carbolic fuchsin; then, without rinsing in water, it is placed for a few seconds in the fluorescein methylene blue solution. Finally it is dipped ten or twelve times in a solution of 5 parts of methylene blue in 100 parts of alcohol. It is then washed witli water and examined. Numerous modifications of the above methods have been proposed, but they possess no special advantage over those given. Herman's method for the staining of the tubercle bacillus is said to possess advantages over the carbol- fiuhsin method. For this stain a three per cent, solution of crystal violet (6B) in ninety-five per cent, of alcohol is combined with a mordant consisting of a one per cent, solution of ammonium carbonate in distilled water; the proportions are one part of the former to three parts of the latter solution. The fixed smear of the material is warmed, then the stain is poured on and held over flame until vapors rise for one-half to one minute. The deeolorization is carried out in ten-per-cent. nitric acid, until the color is prac- tically gone followed by ninety-five-per-cent. alcohol. The smear is then washed, and counterstained with Bismarck brown, methylene blue, or other suitable dye. Staining of Spores. — The cover-glass preparation is treated for some minutes with hot carbolic fuchsin, either on the forceps or by floating on the dye. It should then be rinsed and examined in water. If the spores are colored, the next step is taken; if not, then the heating with the dye is continued until they are stained. The specimen is then decolorized in dilute acid and alcohol until the spores stand out red on a colorless background. • Methylene blue is then applied for a contrast, washed off, and the preparation is ready for examination. The bright red spores are seen within the light blue cells. This method requires considerable care, and every step must be controlled by frequent examinations under the microscope. In order to enable the dye more readily to enter the spore, Moller treated the cover-glass, first, for a minute or two with a five-per-cent. solution of chro- mic acid, after which essentially the above procedure was followed. By repeated passage through the 914 REFERENCE HANDBOOK OF THE Mr.HH \I. SCI1 Bacteriological i •• bnlqac flame <>r by heating with strong sulphuric acid for a few seconds the substance of the spore can be disinte- grated so that on subsequent staining with carl fuchsin the spores will readily lake the dye. Thi treatment, however, destroys tl riginal cell, and hence contrast coloration is not possible. Klein varies the procedure of spore staining given above by adding an equal volume of carbol-fm l solution to a suspension of the spore-bearing organism in physiological salt solution. The mixture is gently warmed for six minutes. Cover-glass preparations are then made, dried, and fixed. They are then de- colorized in one-per-cent. sulphuric acid solution, and counter-stained in the regular manner. This method may be useful in staining those varieties which are especially resistant. By the Abbott method the above order of staining is reversed in that the spores are stained blue, while the bodies of the cells are red. The cover-glass E reparation is deeply stained with methylene blue y heating about one minute at a point where the staining fluid is kept almost constantly boiling. The stain is washed oft in water, then in ninety-tive-per cent, alcohol containing between two- and three- tenths per cent, of hydrochloric acid to decolorize; again wash in water, then stain in aniline fuchsin solution for about ten seconds. Wash, dry, mount for observation. The Gram Stain. — This is one of the most vale methods in bacteriology, since it often serves to dis- tinguish between organisms which otherwise resemble each other very closely. The cover-glass prepara tion is floated for a few minutes on aniline-water gentian violet or on carbolic gentian violet. Heat may be applied, but in that case the excessive staining will interfere with the subsequent decoloration. 'I lie specimen is then rinsed in water and immersed in Lugol's iodine solution for two or three minutes. After rinsing in water it is then placed for a few min- utes in strong alcohol until most of the dye has been washed out. Very dilute eosin solution is now applied for about five seconds. After thorough washing with water it is ready for examination. The organism will appear a deep violet on a pink background. Gram's method is applicable to the bacilli of ant hrax. symptomatic anthrax, diphtheria, leprosy, malig- nant edema, mouse septicemia, rouget, tetanus, tuberculosis, the Fraenkel diplococcus, Micrococcus telragenus, the various staphylococci and streptococci, actinomyces, moulds, and yeasts. It is not given by the bacillus of glanders, typhoid fever, hog cholera. Asiatic cholera, chicken cholera, influenza, plague, Friedlander's bacillus, colon bacillus, gonococcus, rhinoscleroma, and recurrent fever spirillum. The Staining of Flagella. — Special care must be given to the preparation of the cover-glass. The cultures should be made on freshly inclined, moist agar, and should, as a rule, be less than twenty-four hours old. A very dilute suspension of the growth is made, and when spread over the cover-glass is allowed to dry in the air. The fixation must be done with the least amount of heat possible. This can best be done by passing the cover-glass, held between the thumb and forefinger, through the flame. In Loffler's method the specimen is covered with a mordant solution which consists of 100 parts of a twenty-per-cent. tannic-acid solution, 50 parts of a cold saturated ferrous-sulphate solution, and 10 parts of alcoholic fuchsin. The cover-glass is heated over the flame so that vapors are given off for a minute or two. Every trace of the mordant must then be removed by washing with water, and if it has dried down around the edge it should be removed with a knife. The last traces of the mordant can be removed by momentary immersion in absolute alcohol. The specimen is then heated with aniline-water fuchsin for a couple of minutes, washed with water, and examined. The chief difficulty in this method lies in the formation "i a heavy deposit of foreign matl which masks the bad I i i I" i i light modification of thai .,f Loffler. It consists of •_' grams of di \ tannin, 20 of water, I I I and 1 C.C of concentrated alcoholic fuchsin. The aniline water fuchsin is made by adding about .", grams of fuchsin, and 1 c.c. of a one-per-cent. solution of sodium 1 to Kill c.c. of aniline water. Bunge employed a mordant consisting of 7.". parts of concentrated tannin solution. _'."> parts of a tivc- per-cent. olution of ferric chloride, and Mi part- of a com entratedaque * uchsin solution. After stai ing some days hydrogen peroxide I until a reddish dp i is obtained. Pitfield makes use of a Million of mordl and dye. Two solui first prepared: (1) con- sisting of 1 ce. of saturated alcoholic gentian violet and 10 c.c. of saturated aqueous alum; ting of 1 gram of tannic acid and II) <-.i-. of distilled water. two solutions are filtered and then combined. 'I he mixture is heated on I he covei -gla - over a tin for about a minute, and then washed off. Van Ermengem's method i- essentially differ. The cover-glass is wan 1 for about five minutes with a fixing solution consisting of till c.<-. of a twenty-per- cent, tannin solution, 'M) c.c. of two-per-cent. osmic- acid solution, and four to five drops of glacial acetic acid. It is then washed with water, rinsed in alcohol, and dipped for one or two seconds in a sensitizing solution of silver nitrate (one-half to one per cei After this it is placed for a few seconds in the reducing solution which consists of 5 parts of gallic acid, 3 parts of tannic acid, 10 parts of sodium acetate, and ' 350 parts of distilled water. It is again placed in the silver-nitrate solution, in which it is moved about until the liquid darkens, after which the preparation is washed with water, dried, and examined. Of the numerous other modifications which have been proposed that of Gemelli only need be given. Gemeili cleans the cover-glasses in a boiling mixture of potassium bichromate (three per cent.), and sul- phuric acid (five per cent.). After washing in water they are kept in alcohol. Before use each cover-glass is flamed several times. Gelatin cultures developed at 37° C. are said to give the best results. A loopful is transferred to 5 c.c. of water in a watch-glass, and from this suspension a drop is taken and spread over a cover-glass, which is then set aside over calcium chloride to dry. The specimen is then placed for ten to twenty minutes in a one-fourth-per-cent. solution of potassium permanganate. The preparation is now washed well in distilled water, after which it is placed in a three-fourths-per-cent. solution of calcium chlo- ride, to which has been added a one-per-cent. solution of Griibler's neutral red in the proportion of twenty to one. After remaining in this for fifteen to thirty minutes the specimen is washed, dried, and mounted. The method is said to give excellent and sure results without the annoying precipitates which form in the other procedures. Staining of Capsules. — Welch's method consists in treating the cover-glass with glacial acetic acid for a few seconds. The excess of acid is drained off with filter paper, after which the specimen is washed in aniline water gentian violet, and finally in a sodium- chloride solution (0.S5 to 2 per cent.). The heavily stained bacillus will be found to be surrounded by a pale violet halo. Nicolle treats the cover-glass with a mixture of one- per-cent. carbolic acid (10(1 parts) and saturated alco- holic (95 per cent.) gentian violet solution , III parts). It is then washed in absolute alcohol containing one- third its volume of acetone, rinsed in water, dried, and mounted. Hiss' copper-sulphate method consists of preparing films by mixing the organism with a drop of diluted serum on a cover-glass. If the organism has been 915 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES grown upon ascitic or serum medium, the addition of serum is not neeessar_v. the film being made direct from culture. The film is dried in air and fixed with heat. An aqueous solution of gentian violet (5 c.c. saturated alcoholic solution gentian violet to 95 c.c. distilled water) or fuchsin may be used, as stain. The stain is placed on the fixed cover-glass preparation, and carefully heated over a flame for a few seconds until steam rises. The stain is then washed off with a twenty-per-cent. solution of copper sulphate (crystals). The stained preparation is dried between filter papers and mounted for examination. Rosenow's method for the staining of capsules is especially applicable to the pneumococcus and the Streptococcus mucosus. -Make a thin smear of the material upon a perfectly clean slide or cover-glass. In the case of sputum, "if too thick, add sufficient distilled water so that an even spread may be made, or if growth from solid medium (blood agar, Loffler's blood serum) is used, remove a small amount and mix with a drop of serum upon a slide. Spread the material by means of fine tissue paper. When the smear is nearly dry, cover with a five to ten per cent, aqueous solution "of tannic acid for ten to twenty seconds; wash in water and blot; stain with carbol (1 part sat. alcoholic sol. gentian violet, 4 parts five per cent, aqueous sol. phenol) or aniline-gentian-violet, gently heat over flame without boiling for one-half to one minute; wash in water, place in Gram's iodine solution for one-half to one minute, decolorize in ninety-five per cent, alcohol; stain with saturated alcoholic (sixty per cent.) solution of Griibler's eosin from two to ten seconds depending upon the thick- ness of the smear; wash in water and blot. Examine directly, or clear in xylol and mount in balsam. Pneumococci stained by this method appear sharply differentiated from the capsule; the cell-body takes a deep brownish-black, the capsule a pink stain. If the organism is Gram-negative, Loffler's or aqueous methylene blue may be used as a contrast stain. Staining of the Babes-Ernst Granules. — Neisser rec- ommends the following method as a means of differen- tiating the diphtheria bacillus from like organisms. A culture grown on Loffler's serum should be used. Tne specimen is treated for one to three seconds, or a little longer, with the following solution: one gram of methylene blue, 20 c.c. of absolute alcohol, 50 c.c. of glacial acetic acid made up to one liter with distilled water. It is then washed with water and stained with Bismarck brown (two-per-eent. aqueous solu- tion) for three to five seconds. Finally it is washed with water and examined. The blue granules will stand out in the light brown bacilli. Piorkowski heats the preparation for one-half to one minute with an alkaline solution of methylene blue, then decolors for five seconds in alcohol con- taining three per cent, of hydrochloric acid. A one- per-cent. aqueous eosin is applied for contrast, after which the preparation is washed and examined. Impression Preparations of Colonies. — It is very often desirable to reproduce or preserve the charac- teristic surface colonies. The selection of the surface colony is made under the microscope, after which the tube of the instrument is raised and a cover-glass is dropped down upon the colony. Gentle pressure is applied, the cover-glass lifted off, air-dried, fixed, and stained with methylene blue in the usual way. Staining of Protozoa. — The study of the protozoa and kindred microorganisms is so closely associated with bacteriological methods that it will not be amiss to discus^ briefly the more useful stains employed in con- nection with this important class. Many advances have recently been made along this particular line of work which has thrown much light upon diagnosis and i be el iology of disease. Romanowsky' s Chromatin Stain. — This method is extremely valuable for staining protozoal parasites, such as those of malaria and the trj-panosomes. It may also be used for staining Treponema (Spiro- chieta pallidum. When properly carried out it gives an admirable differentiation of the chromatin, which appears red on a blue background. Nocht's modi- fication gives very good results, and is briefly as follows: A solution of one-per-cent. methylene blue and one-half per cent, sodium carbonate is kept at about 60° C. for several days to "ripen." The change which takes place is one of slow oxidation, and as a result a number of products form, among which is the one which is essential to this method. This active red constituent has been designated as methyl- ene azur. To about 2 c.c. of water in a watch-glass two to three drops of a one-per-cent. solution of eosin are added, and then the altered blue, drop by drop, till the eosin tint just disappears. The specimen is floated on this dye for five to ten minutes, after which it is washed and examined. Independently Wright, Leishman, and Reuter arrived at a simple modification. The ripened or polychrome methylene blue is treated with an eosin solution to slight excess. The precipitate, which Reuter has called a methylene-blue eosin, is then filtered, washed, and dissolved in methyl alcohol. This solution can now be obtained from Grubler. Thirty drops of this are added to 20 c.c. of distilled water in a large watch-glass or Petri dish. The spec- imen, which can be fixed with ether alcohol or with formaldehyde alcohol (10 :90), isimmersed in the dye for fifteen to thirty minutes. It is well gently to agitate the liquid from time to time. It is then washed, dried, and mounted. Wright's modification has been recommended by Musgrave and Clegg as giving the best results in staining the ameba of dysentery. The Leishman stain has been prominently brought forward by Wright and Douglass in their staining of white blood cells (phagocytes) while studying the opsonic action of blood serum. As a phagocytic cell stain, this apparently possesses no advantage over Wright's or certain other modifications of the Romanowsky stain. These stains, ready for use, can be procured from dealers. Laveran employs 1 c.c. of a one-per-cent. solution of azur, 2 c.c. of a 0.1-per-cent. solution of eosin, and 8 c.c. of water. The specimen is stained for ten minutes then washed and immersed for two or three minutes in a five-per-cent. tannic acid solution, after which it is washed, dried, and mounted. Giemsa has made several modifications of the stain. The following is one, which, in the hands of Williams and Lowden, has given excellent results in the study of the finer morphological characteristics of "Negri bodies." It is composed of azur II-eosin, 3.0 grams; azur II., 0.8 gram; glycerin (Merck's chemically pure), 2.50.0 c.c; methyl alcohol (chemically pure), 250.0 c.c. The glycerin and alcohol are heated separately to 60° C. The dyes are put into the alcohol, and the glyc- erin is slowly added while stirring. The mixture is allowed to stand at room temperature for about twenty-four hours, when, after filtration, it is ready for vise. The technique followed by Williams in the study of "Negri bodies" was to prepare smears of brain tissue (cortex from near the fissure of liolando. Amnion's horn, and cerebellum), and air-dry. The smear is fixed in methyl alcohol for five minutes. The stain is added to distilled water, which has previously been made alkaline by the addition of one drop of a one-per- cent, solution of potassium carbonate to each 10 c.c. of the water. The stain is used in the proportion of one part of stain to one part of the slightly alkaline water. This solution is poured over the fixed smear at once, and allowed to stand from one-half to three hours, but a longer time brings out the structure better. The stain is washed off in running tap water from one to three minutes, and dried between fine filter papers. In this method of staining, the cytoplasm of the 916 REFERENCE HANDBOOK < )!•' THE MEDICAL BCIENI Bacteriological Technique "bodies" stains blue and their central bodies and chromatoid granules stain a blue-red <> far as this method is concerned, but they can .-till be found by means of Gram's method. Duval has cultivated an organism directly from human leprous tissue which he considers to be B. lepra. Fortius purpose special artificial media are used. He has in- fected such animals as the Japanase dancing mouse, guinea-pig. and the monkey (Macacus rltcsus) with the cultures grown on artificial media. 9. Cerebrospinal Meningitis. — The Diplococcus in- 919 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES tracellularis meningitidis is found in the cerebro- spinal fluid. Hence during life it is necessary to re- move some of the fluid by lumbar puncture. This fluid should be planted abundantly on glycerin, or better on serum agar. Cover-glass preparations made direct will show the typical organism resembling the gonococcus in form and in its presence within the leucocytes. It is not stained by Gram's method, but can be given a double stain by that of Pick and Jacob- sohn, or by the modification suggested by Fraenkel. The dye is made by adding to 20 c.c. of water eight drops of a saturated solution of methylene blue, and then forty to fifty drops of carbolic fuchsin. The dye is allowed to act for five minutes. The cocci are blue on a red background. 10. Pneumonia. — In all pneumonic conditions the blood-streaked sputum should be examined by making simple and Gram stains. In this way it becomes possible to recognize the pneumonic form of plague. Ordinarily, however, pneumonia is due to the Fraen- kel diplococcus and at times to the Friedliinder pneumobacillus. The form, staining, and cultural properties of these organisms permit ready differentia- tion and identification. The lance-shaped diplo- coccus of Fraenkel, as found in the body, is surrounded by a capsule, and is stained by Gram's method. The colonies and cultures on glycerin agar are very faint and dewdrop like, and tend to die out in a few days. Their vitality and virulence are best preserved by cultivating them on rabbit blood or serum agar. Calcium broth may be used for the same purpose. In doubtful cases the material should be injected under the skin of the ear of a rabbit or subcutaneously in white mice. If death results the diplococcus will be found in large numbers in the heart blood and organs of the animal. 11. Rabies. — The cause of this disease is as yet unknown, but it is to be found, in pure condition so to speak, in the brain and spinal cord of the affected person or animal. The diagnosis rests upon animal inoculation with such material. A few drops of a suspension of the brain or cord are injected subdurally into a rabbit or guinea-pig. The method has been already described. The histological changes in the nervous system are very slight, and it has been suggested that the diag- nosis of rabies may be hastened by making an examina- tion of sections of the cord and ganglia. The lesions are not sufficiently marked in all cases to permit diagnosis, and for that reason this method should not be relied upon to the exclusion of the only positive test, that of animal inoculation. The work of Williams upon "Negri bodies" has called attention to the fact that a rapid diagnosis may be made from smear preparations of the brains oi animals which have suffered from rabies. After a long series of observations, both clinical and experi- mental, the Department of Health of New York City has adopted this method of diagnosis. Their present method of procedure is as follows: Make smear preparations from the cortex taken from the region corresponding to the fissure of Rolando, Amnion's horn, and the cerebellum. Fix the smears while moist in a solution composed of methyl alcohol (pre- viously neutralized with sodium carbonate) containing one-tenth of one per cent, of picric acid. After allow- ing to act about one minute, pour off the fixing fluid, and blot with fine filter paper. The stain is prepared by adding five drops saturated alcoholic solution of methylene blue, and one drop saturated alcoholic solution of basic fuchsin, to 10 c.c. distilled water. This should be freshly prepared just before using. Pour stain on slide; warm until it steams; pour off; rinse smear in water; blot and allow to dry. Upon examination under the oil-immersion lens, the "Negri bodies" will be found in the nerve cells; some also are free. The cytoplasm of the "bodies" takes a distinctive red color; their inner structures a dark blue. The nerves are light blue, and the blood cells a pale salmon-red. At room tem- perature this stain is not permanent, but it has the advantage of being a very rapid method for the diagno- sis of rabies. If "Negri-bodies" are not found by this method of examination, some of the brain tissue of the suspect animal is then inoculated into guinea-pigs by the regular procedure, as a further aid in diagnosis. 12. Tetanus. — The point of inoculation must be found first. This may not always be easy, for the original wound may have healed over. The portal of entry may be a bad tooth, or the wound produced by an old rusty nail, a splinter of wood, or the powder grains of a pistol. Cover-glass preparations should be made from the pus, if there is any; and, if not, from such serum, blood, or tissue as can be obtained from the wound. They should be stained with carbolic fuchsin. The specimen should be examined for "drum sticks" or rods with terminal spores, and particularly for the presence of rather narrow, long bacilli. These are present even when no spores can be found. Cultures should be made on glucose litmus gelatin, and at the same time a series of glucose agar plates should be made and developed at 37 C°., either in hy- drogen or in the pyrogallate apparatus. The original tissue should be planted under the skin of a white mouse and of a guinea-pig. The cultures when developed are carefully searched for the 'drum-stick forms. 13. Tuberculosis. — The pulmonary form is usually recognized by an examination of the sputum, prefer- ably that which has been collected in the morning on rising. The cheesy particles, if such can be recog- nized, should be picked out by means of the wire and spread over the cover-glass. The specimen is then stained either by the Ziehl-Neelsen or the Herman method. The organisms if present are readily recog- nized by their contrast color against the counter- stained background. The same method is employed in the examination of pleuritic fluid, pus, urine, milk, etc. In all these examinations, however, two facts should be borne in mind. In the first place the tubercle bacilli may be present, but in such small numbers that they escape detection. Again, acid-resisting organisms, such as the leprosy, smegma, timothy-grass bacillus, etc., may be present, and may be easily mistaken for the tubercle bacillus. In either case it is the animal experiment which will serve to remove the doubt. When the tubercle bacilli are few or doubtful, it is well to submit the material to preliminary centrifugation; or first subject the material to antiformin digestion. This preparation consists of a strongly alkaline solution of chlorinated soda, which has the power to dis- solve such substances as mucus, animal cells fibers, etc., also most bacteria other than those which are acid-fast. In the case of sputum, good results may be had by mixing equal parts of sputum with thirty per cent, of the antiformin, and digesting at room temperature for one hour. Centrifuge, and decant the supernatant fluid from the sediment. The sediment is washed with sterile distilled water, and again cen- trifuged; the sediment may be stained for the tubercle bacillus or injected into a guinea-pig. If the anti- formin digestion is permitted to continue too long, the tubercle bacillus loses some of its staining ability, also its viability. The injections should be made subcutaneously into the guinea-pig. If tubercle bacilli are present in the material used, even if so scarce as to be unrecognized by the microscope, the animal will develop the disease and will die in the course of a month or two. The tuberculous organs and glands can be examined then for tubercle bacilli, and cultures can be made on glycerin agar, potatoes, and on either Dorset or Lubenau egg medium. Hesse's Heyden agar also proves quite satisfactory for isolating the 920 REFERENCE HANDBOOK OF THE MEDICAL SCI] Bacteriological TeduUqae tubercle bacillus from sputum.. The acid-resisting bacilli, other than the tubercle bacillus, are not fatal to animals, and, moreover, the histological changes which they induce are quite different from those cau ed by the tubercle bacillus. 14. Typhoid F< ver. — The verification of the diagno- sis is usually ma. \ number of infections due to moulds and allied forms and also to yeast-like bodies have been de- scribe,!. The former are represented by the strepto- thrices, or. more correctly, by the actinomyces of Madura foot and of cattle farcy. The yeast or blast o- mycotic affections have been noted in certain forms of dermatitis, and may even be systemic in charai In all these diseases the examination of the pus and of sections of t issue, as well as the culture of the organ- ism, must be carried out. 16. Protozoal Diseases. — Several very important diseases are due to organisms of this class. The ex- amination for amebas in tropical dysentery has al- ready been touched upon. The sporozoa include among others the Plasmodium of malaria, the piro- plasma of Texas fever, and of horses, sheep, and dogs. The flagellata cause the various trypanosomatic diseases, such as the surra of Asia anil of the Philip- pine Islands, nagana or the tsetse-fly disease of South Africa, dourine or "maladie du coit" of the Mediter- ranean littoral, caderas of South America, the (1am- bian fever and the sleeping-sickness, the last two being diseases of man. Moreover, many animals harbor in the blood parasites of this group, as in the case of the wild rat. In all suspicious cases the blood should be examined for these two groups of organisms. Tin- plasmodium of malaria is found especially within the blood cells. The trypanosomes are free in the plasma. Tho blood may be examined direct under the cover-glass, or in hanging drop, or in a Rainier slide. Stained preparations can be made with methylene blue, thionin, or best with some modification of the Roman- owsky method. The preparation of the specimens and the staining methods have already been described. The trypanosomes of the rat and of nagana. have been cultivated artificially by Nbvy and McNeal. Their presence is best detected by direct examination of the blood, though at times they may be very difficult to find, and may require daily examinations for several weeks. DETERMINATION of TnE Thermal Death Point of Bacteria. — In this work and also in testing disin- fectants it is necessary to have almost homogeneous suspensions of the organism to be tested. Water suspensions should be used first, and later those of bouillon, serum, etc. The liquid is introduced by means of a bulb pipette into the tube of an agar culture. The growth is rubbed up as much as possible and the suspension is then transferred to a sterile glass-wool filter. In this way the masses of bacteria are removed. The cloudy filtrate may be used as such, or it may be diluted so as to have fewer organisms in the test. It may be used as such for determining the action of moist heat and for testing disinfectants. 921 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Again, for dry-heat work and for many disinfecting tests the suspension is allowed to dry upon the surface of sterile glass slips, glass or garnet beads, silk threads, muslin squares, etc. To test the action of dry heat a number of cover- glasses on which the test organism has been dried are placed in a sterile Petri dish and exposed to a given temperature. At given intervals a specimen is re- moved and planted in bouillon. To test the action of moist heat the best procedure is to draw up the liquid into sterile capillaries, as shown in Fig. 603. The tube is sealed below and above the liquid. The advantage of this method lies in the fact that the heat promptly penetrates every part of the suspension. A number of tubes thus equipped are placed in a water-bath, the temperature m:) t> Fig. 603. — Filling of Capillary Tubes for Thermal Death-point Determinations. c. Tube filled ready to be sealed at x; 6, emptying of tube. (Novy.) of which is kept at a constant point by means of a regulator. At intervals a capillary is removed, cooled, opened at one end, and the contents are ex- pelled into a tube of bouillon by gently toucliing the closed end to a flame. Testing of Chemicals. — In this work it is necessary to distinguish between the antiseptic and the disin- fecting action of a substance. The former refers to the amount of the substance which wid inhibit the growth, but not necessarily kill the organisms. The latter implies the actual destruction of the test object. Obviously a substance which will kill bacteria, when diluted sufficiently will merely restrict their growth, and when the dilution is excessive will have no action whatever. The antiseptic action is determined by adding to the suspension in bouillon varying amounts of the chemical so as to make different dilutions, for ex- ample: 1 in 500, 1 in 1,000, 1 in 5,000, 1 in 10,000, etc., solutions. The tubes thus equipped are then placed in the incubator for several days. The very weak solutions will show growths, while the very concentrated ones will show none. The amount which just inhibits the growth represents the an- tiseptic power of the substance. The germicidal action of a gas, such as formalde- hyde, is determined by exposing cover-glass prepara- tions, silk threads, bit of muslin, etc., impregnated witli the suspension, dry and moist, to the action of the gas in a tight room. At the end of the exposure the preparations are transferred to sterile tubes of bouillon and incubated. The germicidal action of liquids is ascertained, either by adding the solution to the bacterial suspen- sion or by immersing in the solution the dried cover- slip preparations mentioned. In the former case, at stated intervals, a small loop of the liquid is trans- ferred to bouillon, while in the latter case the slip or thread is first rinsed in sterile water and then placed in the bouillon. The Serum Agglutination Test. — The serum of an animal which has been immunized to a germ when brought into contact with a suspension of that germ will cause the organisms to gather in masses. The fact is utilized in the Widal test for typhoid fever. A drop of the scrum from a typhoid patient is diluted with tin, twenty, thirty, fifty, one hundred drops respectively of water in a watch-glass. A drop of each mixture is then transferred to a cover-glass and inoculated with a very small amount of a fresh agar culture of the typhoid bacillus, care being taken to avoid an excess of the organisms. Hanging drops are then made and the preparations examined under the microscope. The limit of the reaction is in- dicated by the dilution which is just able to cause paralysis of motion and clumping in one hour. In- stead of diluting with water some prefer to use a very young bouillon culture. The agglutination test is most delicate when carried out under the micro- scope. Very good results, visible to the unaided eye, may be obtained by adding the serum to bouillon culture of the organism. The tubes thus treated should be set aside for some hours at 37° C. when the agglutinated masses will settle to the bottom and leave the liquid clear. When applying the test to a suspected case of typhoid fever it is not always possible to obtain large amounts of the serum. In such instances the blood may be placed in single drops on a sheet of filter paper, or, better, tinfoil. The dilutions can then be made with these drops of dried blood as with the serum itself. The appli- cation of this test to the recognition of the typhoid bacillus in drinking- water, feces, etc., has been given. The Complement Fixation Text. — This test is one of importance not only in clinical diagnosis, but also in general bacteriology. It affords a most delicate means, under proper conditions, for the differentiation of varieties of a bacterial species. However, its accuracy depends much upon the proper preparation of the materials to be used in the test and the methods used in carrying it out. The test is based upon the so-called Bordet- Gengou phenomenon. Those investigators observed that when an antigen, its specific antiserum, and com- plement were brought together and incubated, the latter component was fixed or bound — it could not functionate again in similar reactions. As an indica- tor of this complement binding with bacterial anti- gens and their antisera, sensitized red blood cells are added later to the above combination. If the comple- ment is bound no hemolysis occurs on the second incubation, but if not bound it combines with the sensitized blood cells and causes a definite hemolysis. As evident this test can be used for the recognition of specific antibodies, or, conversely, the specific anti- gens giving rise to antibodies. In order to carry out the test, say for example, with the serum of an animal immunized against a given organism, the following materials are necessary: (1) normal red blood cells; (2) a specific hemolytic serum against the blood cells; (3) complement; (4) an antigen prepared from the specific organism. Usually the normal blood cells are those drawn from the jugular vein of the sheep. After defibrination of the blood the cells are washed several times in physiological salt solution by the centrifuge method to remove all traces of serum. The specific hemolytic serum may be derived from a rabbit by giving repeated injections of thoroughly washed sheep erythrocytes. Generally an active hemolytic serum is obtained if three or four injections are given intraperitoneally, spaced about three days apart; the initial injection may be 5 c.c. packed corpuscles; the doses are gradually increased until the final injection amounts to 15 or 20 c.c. The animal should not be bled until about ten days after the last injection. The blood is allowed to clot, then the clear serum is separated and placed in sealed bottles for use. The serum is inactivated by heating for thirty minutes at 56° C. before standard- izing. It is standardized by taking decreasing amounts (i.e. 0.01 to 0.001 c.c.) and placing in a series 922 REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriological Technique of test tubes; to each tube n ]o c.c. complementing serum is added, then all brought to a constant volume with 0.9 per cent, sodium chloride solution, aftei which one centimeter of 5 per cent, blood suspension is added; the system is incubated in water bath for one hour at .17° ('. After removal from the water bath, the tubes are placed in an ice chest until the intact cells settle to the bottom of the tube. That amount of the hemolytic serum which just completely dissolves all of tin- corpuscles in the test tube is called the hemolyt ic it amboceptor unit. For complen freshly clotted out guinea-pig serum best serves the purpose. In the complement fixation test proper, the normal guinea-pig scrum should also hi' standard- ized since the complement content is variable. This is done by finding that amount (one unit) which just produces complete hemolysis when added to a mix- ture of one unit of hemolytic serum, and 1 c.c. of 5 per cent, suspension of sheep erythrocytes, after incubating one hour at 37° C. In preparing the bacterial antigen for the test, the best results are had by using a filtrate (Berkefi I I derived from slant agar growths which have been partially autolyze.d in distilled water. The antigen must be standardized against a definite amount (0.1 to 0.2 c.c.) of a specific antiserum in order to determine the amount which will fix perfectly wit hout showing anticomplementary action in the regular test. The quantity thus found is used as the antigen unit in the test proper, but should be sufficiently low that double the amount will not be anticomplement- ary. Having provided and standardized the neces- sary components for the complement fixation test, it is carried out as follows: to a series of test tubes are added decreasing amounts (0.10, 0.09, 0.08 .... 0.01 c.c.) of the inactivated serum for examination; to each tube one unit of the bacterial antigen is added; then two units of the complement; finally, sufficient physiological salt solution is added to bring to a con- stant volume throughout. The following controls are also run in the complement fixation test: one tube containing double amount of the bacterial antigen used in the series, plus the hemolytic system; one tube with double the highest quantity of antiserum used in the series, plus the hemolytic system; one tube with a known positive serum, and one with a negative serum, both of which are carried through in parallel with the test serum; finally, one tube with only the regular hemolytic system. The test series (with the positive and negative control sera) of tubes are incubated for thirty- minutes in water bath at 37° C. After incubation to each (including control are added two or three units of the hemolytic immune serum (amboceptor), and then 1 c.c. of a 5 per cent, suspension of sheep erythrocytes. The tubes are shaken, and again returned to the water bath at 37° C. for one hour. At the end of this period they are re- moved and placed in an ice chest until the blood cells settle to the bottom of the tube, then the readings are made. If the controls are satisfactory, the results of the test are recorded. .Since in the ease just con- sidered, the serum being tested was derived from an immunized animal, some if not all of the tubes would show no hemolysis. In those showing no hemolysis, the complement was bound by the antigen-antibody complex, and none remained free to act upon the sen- sitized corpuscles added later. If the serum under examination were not of especially high value, those tubes of the series which received the smaller quanti- ties of the serum would show hemolysis — that is, free complement which acted with the hemolytic system present. Preparation of the Soluble Bacterial Toxins. — Solu- ble or extracellular toxins are produced by a number of pathogenic bacteria (B. diphtheria-, B. tetani, B. botttlini, etc.) when grown upon proper culture media, under favorable conditions. For the purpose of practical immunization of animals, it is necessary io have highly eon. entrated to i fore, pre- cautions mu i he taken in cultivating, to brink; about the proper conditions. Vltl .■. ,,f toxin production is as v.i QO | fully understood, has shown that certain media are more " able than ot he, ,,i tai trains of I be organism vary in their ability to elaborate t< In the preparatii f diphtheria toxin lark recom- mends as a suitable culture medium a nutrient broth prepared in the regular manner from young veal, i ■• each liter add two per cent peptone | \\ sufficient alkali to give an alkalinity equivalent to the addition of 8 c.c. of normal solution of potassium hydrate above the m lU8 , Sufficient nutrient broth is placed in thin layers 'a* mehes deep) in large-necked Erlenmeyer Basks, to access of air. After inoculation with H. the flasks are incubated between :;.V and : '0° C. PI on of toxin is p cut between the tilth and eighth days of bacterial growth. After the tenth day, at incubator tempera- ture, tin' toxicitj decreases mop. or less rapidly, o to its labile character. After one week's growth, a test for purity of culture is made by microscopical and culture methods. If found pun", the bacteria are killed by the addition of ten per cent, of a five-per- cent, solution of carbolic acid. After standing for forty-eight hours, the dead bacilli settle to the bottom, and -t of them may be removed by filtering the broth through ordinary Sterile filter paper. Bottles are filled with the so-called toxin, sealed, and stored in the ice chest until n led. A hypodermic in- jection of 0.01 c.c. or even less should kill a 250-gram guinea-pig. The bacillus of tetanus also produces a very power- ful poison under artificial means of cultivation. Since the bacillus of tetanus is anaerobic in character, its cultivation for toxin production must he varied from that of the diphtheria bacillus. Park's met ho. I consists in using a nutrient beef broth of slight alkalinity, containing one per cent, peptone t Witt. , 0.5 per cent, common salt, and one per cent, glucose. The broth thus prepared is placed in flasks until they are about two-thirds filled, then sufficient molten paraffin (melting-point about 45° C.) is added to form a semi-solid covering one-half to one inch in thickness. The whole is sterilized and when ready for use the flask is sufficiently heated to liquefy the paraffin layer. A shake culture of B. tetani in agar is dropped in the warm medium. The heated broth will cause the agar to dissolve and liberate the organisms and spores. When cool the paraffin hardens over the broth and seals it off from the air, thus producing anaerobic conditions. The agar shake culture is best removed from the test-tube by quickly heating until the agar about the wall dis- solves: then it may he poured into a flask. Precau- tion should be exercised to prevent outside con- taminations. The culture is incubated at a tem- perature of 37° C. for five to six days. After the necessary tests for bacterial purity are made, the liv- ing organisms and spores are removed by first lil- tering through paper pulp (funnel and suction), then through a Berkcfeld filter. To the filtered toxin 0.5 per cent, carbolic acid is added; flasks are then completely filled, sealed, and kept in a cool tlark place. The strength of this toxin is quite variable, much depending upon the conditions of prep- aration. According to Park, under best conditions the amount of toxin produced in cultures on the fifth day may be such that 0.000005 C.C is a fatal dose for a "fifteen-gram mouse. Tetanus toxins as prepared by the above method may show such a degree of toxicity that 0.001 to 0.0001 c.c. will cause death within four days to a guinea-pig weighing from 300 to 350 grams. The other soluble bacterial toxins may be prepared in a similar manner, but the composition of media and 923 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES conditions must be altered to meet the special re- quirements of the organism under cultivation. Methods of Immunization. — Only the general princi- ples of active immunization can be considered. The injections are made subcutaneously, intraperitoneal]}', or intravenously. When immunizing a horse for the production of antitoxin serum, the injection of toxin should always be made subcutaneously. Experience has proved that the antitoxin is formed much more rapidly and reaches a higher concentration in the blood under such procedure. The primary dose of toxin for a normal animal must be very small. An initial dose of 0.01 c.c. of diphtheria toxin has proved fatal to a horse. Therefore, in immunizing a previously un- treated horse, it is necessary to begin the injections of diphtheria toxin (also tetanus toxin) with a dose under one one-hundredth of a cubic centimeter, to keep within bounds of safety. A repeated injection of toxin should not be given until the animal has practi- cally recovered from the reactionary symptoms of the previous dose. In the routine immunization of horses against diphtheria Park recommends that the initial dose be about 20 c.c. of fairly strong toxin; the second and third doses are slightly increased. But with each of the first two injections about 10,000 units of the antitoxin is given. In this way the animal is protected until it has an opportunity to elaborate its own anti- bodies, then the injections of antitoxin should be dis- continued. This procedure aids in bringing an animal without danger up to a high degree of immunity in a relatively short time, as compared with the older method. In either case, after a few months' treat- ment, a horse may withstand several hundred cubic centimeters of highly potent toxin, at a single in- jection, without serious results. When a soluble poison is injected, a true antitoxin develops in the animal and is present in the blood and hence in the serum. This is the case in diphtheria, tetanus, and venom immunity. On the other hand, when the solid cell is injected, the serum may acquire anti- infectious properties, the best instance of which is seen in the antipest serum. The organisms may be killed by exposing them to the action of ether, of chloroform, or of moist heat at 60° C. In special cases the attenuated living germ is used, and at times even the most virulent form is employed. By the injection of cells other than bacteria, diverse cytolytic sera are obtained. Thus the injection of the red blood cells gives rise to a hemolytic serum. The tempera- ture and the weight of the animal must be taken daily, since they afford the best indication of the condi- tion of the animal. Testing the Strength of Antitoxin. — The strength of an antitoxin is expressed in immunity units. A unit, according to the old definition of Behring and Ehrlich, represents that amount of serum which will be just sufficient to protect a 250-gram guinea-pig against 100 minimum fatal doses of a given diphtheria toxin. Thus if 0.1 c.c. of serum protects against this dose of poison, then it will contain one immunity unit, and 1 c.c. of such serum will contain ten immunity units. To determine the antitoxic value of a serum accord- ing to the earlier method, the first essential is to ascertain the minimum lethal dose (M. L. D.) of the toxin, by which is meant the amount of toxin which will kill a 250-gram guinea-pig on the fourth or at most on the fifth day. Varying amounts of the serum are then added to portions of the toxin representing 100 minimum fatal doses. These mixtures are then injected into guinea-pigs of the weight given. That fraction of a cubic centimeter of the serum which just suffices to save a guinea-pig under these condi- tions represents, as stated above, one immunity unit. This method is subject to some error, inasmuch as it has been found thai a serum which has been tested against one toxin will show a different value when tested against another. This is due to the fact that the toxin undergoes changes on keeping, and is con- verted into a non-poisonous body or toxoid, which, however, retains the power of combining with the antitoxin. For this reason Ehrlich proposed a new method of testing the antitoxic value of a serum. A standard dried antitoxin is made the basis of the measurement. This is diluted so that a gn r en amount just represents one immunity unit. The test dose (L +) of toxin is then ascertained and represents the amount of toxin which, mixed with one immunity unit of serum, will cause death on about the fourth day. The serum to be tested is then diluted, mixed with the test dose of the toxin, and injected into a guinea-pig. If the animal dies in a day or two it is evident that the serum contains less than one immu- nity unit. If, on the other hand, it lives for seven or eight days, or even recovers, it shows that the amount of serum taken contains more than one unit. By using suitable dilutions of the serum, eventually tin; point will be reached where the amount taken will represent exactly one unit. It is possible to secure an antitoxic serum from horses immunized against diphtheria toxin which contains over 1,000 immunity units in 1 c.c. But this is quite exceptional. Usually the serum of horses, as com- monly immunized, averages between 300 to 500 units per cubic centimeter. Gibson succeeded in preparing a concentrated preparation of diphtheria antitoxin by precipitating the proteins, and separating the globu- lins from antitoxic serum by the addition of certain salts. The globulin fraction which contains the anti- bodies, is finally freed from the salts, etc., by dialysis. By the Gibson method a preparation (fluid) may be obtained which contains 1,500 to 1,800 units per cubic centimeter. Recently Banzhaf has improved the method to the extent that the protein concentration is materially reduced, while at the same time the anti- toxic content is increased. By this improved method a preparation may be obtained which contains 3,000 units per cubic centimeter, with a protein con- centration of only twenty per cent. These so-called antidiphtheritic globulins or concentrated antitoxins are prepared by different serum laboratories. Opsonic Technique. — The fact that certain cells of the body will take up and destroy microorganisms has been known for years. The phagocytic theory of immunity is based upon this phenomenon. Dcnys and Leclcf were the first to demonstrate the presence of a substance in immune serum which made the corre- sponding organism more susceptible to phagocytosis by leucocytes. They showed that this substance acted upon the organism and not on the leucocytes. Later Wright and Douglas called attention to the fact that such sensitizing substances are present in fairly constant amounts in the normal blood. This substance, which they call opsonin, exists in smaller amounts or widely fluctuating amounts in the blood of a patient suffering from specific bacterial infec- tion. The opsonic content may be increased by prop- erly vaccinating with killed cultures of the specific organism. Bacterial vaccines are beginning to play an important role in the newer therapeutics. It is obvious that such means of treatment must be carefully controlled, or, instead of being of material aid to the body, they become a damaging factor. Therefore, in order to follow the vaccination treat- ment, a means must be found by which a fairly ac- curate measurement can be made of the opsonins in normal blood and in the blood of a patient suffering from any bacterial infection. Wright and Douglas have practically overcome this difficulty by a tech- nical method by which they derive the so-called "op- sonic index." This "index" simply shows the relation existing between the opsonic content of a patient's blood as compared with the opsonic content of the blood of a normal person. The general method used in deriving the opsonic index calls for the following materials: Blood serum 924 REFERENCE HANDBOOK OF THE MEDICAL SCI] \' I - Bacteriological Technique from patient, control scrum from normal person, normal trashed corpuscles, and the bacteria] emulsion. The same technique is used in preparing serum from both the patient's and normal blood. A puncture is made in the lobe of the ear or one of the tinners with a needle, ami pressure is used to cause the blood to How. When the blood begins to exude, eight or ten drops are drawn up into a pipette, and at once transferred to a small test-lulie, about one- quarter inch in diameter and two inches in length. The blood is allowed to clot, thus permitting the scrum to separate. To secure t he leucocytes, the blood is draw n directly into a small test-tube containing about H» c.c of a one-and-one-half per cent, solution of sodium citrate in physiological salt solution. This solution prevents the blood from clotting. One cubic centimeter of blood will furnish a sufficient number of leucocytes for the test. The corpuscles are centrifuged until the solution above the packed cells appears transparent . The solution is carefully removed with a capillary pipette, then about 10 c.c. of physiological salt solu- tion are added and well shaken to wash the cells. It is centrifuged again to throw down the corpuscles, and the salt solution is removed with capillary pipette. Care should be taken not. to disturb the superficial creamy layer of blood cells, as this layer contains the greater share of the leucocytes. When the fluid has been removed, the leucocyte layer of cells should be taken up carefully with a capillary pipette, and the thick emulsion reserved for the test. Blood which shows any clotting must be rejected. The bacterial emulsion should be a uniform suspen- sion, but it is very difficult to avoid some clumping of organisms. Different organisms vary in this respect. Tubercle bacilli are extremely hard to get into a uni- form suspension. To prepare an emulsion of such organisms as staphylococci, streptococci, pneumo- cocci, and such bacilli as typhoid and colon, cultures are grown on the most favorable agar medium, and used fresh, i.e. not older than twenty-four hours. A portion of the culture is removed with a medium- sized platinum wire, and transferred to a small test- tube containing 3 or 4 c.c. of physiological salt solu- tion. The mass of organisms is carelully rubbed with the wire against the wall of the tube at the surface of the salt solution until a turbid suspension results. Cen- trifuge until the larger particles of bacteria are thrown down, but discontinue before the finer suspension is sedimented. Experience will indicate the proper de- gree of turbidity which is desirable. Wright recom- mends that the bacterial suspension be such that four to live cocci are found for each cell in the final mixture. For emulsion of tubercle bacilli some workers culti- vate the organism on glycerin agar and kill the organ- isms by exposure to direct sunlight for twenty-four hours, or by other means. Some of the growth is re- moved from the culture tube, and placed in a small agate mortar, where it is thoroughly rubbed up with 1..") per cent, salt solution. The resulting suspension is centrifuged to remove clumps. Other workers prepare their emulsion of tubercle bacilli from dried and ground-up bacilli. In preparing the emulsion, the procedure is the same as the above. In each case when the emulsion is finished, the upper portion is remove from the centrifuge tube, with a pipette, and reserved for use. Wright states that the tubercle emulsion should be of such thickness that one or two organisms are found to each cell in the final smear. Now, having prepared the necessary materials for the work, the next step is to measure out the blood cells, serum, and bacterial emulsion for mixtures. Best for this purpose is a pipette made by taking glass tubing with about five millimeters internal diameter and about fifteen centimeters in length. It is drawn out in the flame in the same manner as described under Pasteur pipettes (Fig. 5096, 6), with the exception that no end constriction is made. The capillary portion of each should i»- about twelve to fifteen centirm long and about one millimeter in diameter. A rubber nipple, such as is used on an ordinary medicine dropper, is slipped ovei the large end. The capillar; cud IS cut off squarely and a mark IS made with a glass marking pencil about three to four centimeters from the end. By mean, c ■ f the nipple, Quid can easily be drawn up into the capillary tube. The mix- ture is made by drawing up the heavy suspension of blood corpuscles (containing leUCOCytl I <" the pencil mark; a little air is drawn in by raising the blood column, then an equal volui f serum is drawn in by tilling up to t he pencil mark; again an air bubble is allowed to enter; then finally an equal volume of tin' bacterial suspension is drawn in. In this way the different suspensions can be equally and accura measured. The whole content is blown out of the pipette on a clean, hollow-ground slide, where it is thoroughly mixed by drawing up and ejecting from the pipet 1 1> several times. Finally, the whole mixture kept free from air bubbles is drawn up into the pipe! te and the capillary end is scaled olf in a flame. The pipette containing the mixture is placed in an incu- bator at ::7 ('.for fifteen minutes to permit phagO- < \ tic action to take place. After removing from the incubator the sealed tip of the pipit tc is broken off, and the suspension is well mixed on a clean hollow- ground slide. Drops of moderate size are placed upon each of a number of clean slides. Each drop is spread by means of the end of a second slide, as is done in ordinary blood work. The smear is allowed to air- dry completely, then stained with aqueous methylcne- blue solution, or with a polychrome dye such as the Wright or Leishman stain. In the case of tubercle bacilli the films are fixed in saturated aqueous solution of mercuric chloride ten minutes. The films are washed in water, stained with Czaplew T sky's carbol- fuchsin solution, and again washed in water. They are decolorized in two-per-eent. sulphuric acid, washed well, and counterstained one minute with one-per- cent, aqueous solution methylene blue. The stained preparations are dried and examined under high-power objective. The bacillary index is found by taking the total number of phagocyted bacteria counted in a series, and dividing it by the number of leucocytes making up the series. Fifty or more leucocytes should make a series. The opsonic index is derived by divid- ing the value (bacillary index) of the patient's serum by the value found for the normal serum used as con- trol. It is an advantage to collect the normal serum from three or four healthy persons and mix all together. This gives more reliable results in finding the opsonic value for the normal condition. In making counts for the opsonic index, the per- sonal equation is frequently pronounced, but by con- tinued experience this factor ma}' become lessened and fairly constant. It also must be noted that marked discrepancies exist between results of ex- perienced workers when estimating the opsonic index of the same sample of serum. Simon recommends that the percentage of phagocyting leucocytes be estimated in connection with the bacillary index. He states that this will act as a check upon the bacillary index, and will reveal errors in counting. A close correspondence exists between the bacillary index (Wright) and the percentage index of Simon. Examination of air. — The bacteria which chance to be present in the air are in a dried condition, and tend to settle when the motion of the air is lessened. The simplest method consists in exposing a plate of gelatin or agar to the air for a given length of time. Si ime of the organisms settle on the gelatin and eventually give rise to colonies. Koch improved slightly upon this by placing the gelatin plate in the bottom of a sterile cylinder of known volume. After opening the cylinder in a given locality it is closed with a cotton plug and set aside, when the organisms contained in 925 Bacteriological Technique REFERENCE HANDBOOK OF THE MEDICAL SCIENCES that volume of confined air settle to the bottom on the surface of the plate. The results, it will be seen, are crudely quantitative (Fig. 604). Hesse's method consists in drawing the air through a large Esmarch roll tube (Fig. (305). The volume of the air drawn through can be de- termined from that of the aspirating bottles. The bacteria in the air im- pinge upon the gelatin surface, where they develop into colonies which can be counted and studied. The apparatus of Petri, although very expensive, may be said to give the best results. It consists in the first place of an air pump, which automatically registers the movements of the piston, and thus gives the volume of the air which has been drawn through. The air is aspirated through a tube (Fig. 606) containing several layers of sterile sand. The suspended bacteria are thus held back. At the close of the operation the sand is transferred to a Petri plate, where the bacteria will form colonies and thus become accessible for study. Instead of sand, Sedgwick and Tucker employed a filter of sugar. The special tube employed by them is shown in Fig. 607. After the air has been drawn through, the sugar is tapped down into the wide portion of the tube, then gelatin is added and warmed Fig. 604. — Koch's Cylinder for Air Analysis. Fig. 605. — Hesse's Apparatus for Air Analysis. until the sugar dissolves, after which an Esmarch roll culture is made in the same tube. Other workers have filtered the air through liquid media or through gelatin. The most convenient form of apparatus of this kind is that of Wurtz, shown in Fig. 608. A suitable amount of gelatin is placed in the sterile tube, then a known volume of air is drawn through, after which the gelatin is solidified over the inner wall of the tube, thus forming a roll culture. Examination of Soil. — By means of a small sterile platinum spoon a definite volume of the soil may be transferred to a Petri plate, where it is thoroughly 926 mixed with the medium. The colonies which develop can then be examined. In this way it is possible at times to demonstrate the presence of the anthrax bacillus in the soil of an infected locality. The de- tection of other pathogenic bacteria, as for instance those of tetanus and malignant edema, can best be made by introducing a quantity of the soil under the skin of a guinea-pig or rabbit. Examination of Water. — This is a very important procedure, and an enormous amount of work has been done to perfect the methods of work. The method followed will necessarily depend upon the immediate \ i /* Fig. 606. Fig. 607. Fig. 60S. Fig. 606.— Petri Sand Filter for Air Analysis. Fig. 607. — Sedgwick and Tucker's Aerobiocscope. Fig. 608. — Wurtz's Apparatus for Air Analysis. object in view. Thus the detection of the cholera, vibrio is carried out in a different way from that used for the colon bacillus. The isolation of the cholera and typhoid organisms from water has already been described. The water which is to be tested bacteriologically must be received into a sterile glass-stoppered bottle, and should be examined at once. If the examination is not carried out at once, the bacterial count will not be reliable. Samples of highly polluted water, when kept cool for some time, show a marked de- crease of intestinal organisms. The first step in the examination is to make gelatin plates. By means of a sterile pipette 1 c.c. of water is added to a tube of gelatin, mixed thoroughly, and the gelatin is then poured out into a Petri plate. In the same way plates are made with 0.5 c.c. and with one drop of the water. The gelatin plates are developed at 20° C. for several liKFEItEXCH IlAXlU'.ooK < >F Till: MEDICAL SCIENCE K.ii lrrlul\ sis days. Tin' colonics are thru counted and examined in the usual way. When only a few colonies are pres- ent on a plate they can be readily counted with the eye. When the number is Large special counters are made use of. That of Wolffhugel (1 ig. 609) is ruled in squares of one centimeter and fractions thereof. Another form is that of I.afnr. A very useful and cheap substitute is mad.' by printing the divided circle on card paper. To make a count, the number of colonies in ten or more squares is ascertained, and the average per square centimeter is obtained. The ana of the gelatin on the plate is taken and then the total number of colonies on the plate determined, and the result is expressed per cubic centimeter of water. Fig. 609. — Wolffhugel's Colony Counter. Instead of using Petri plates, the Esmarch roll tube can be made. To count the colonies in such a tube Esmarch devised the counter shown in Fig. G10. When the number of colonies is likely to be ex- tremely large, as in the examination of pollute,! water. it is advisable to dilute a portion of the sample with a known volume of sterile water. If the colonies are very numerous on a plate, the counting can be carried out best under a microscope. Ehrlich stops are placed in the eye-piece or the special Ehrlich ocular may be used. The size of the opening in the ocular must be determined by means of a stage micrometer. The average number of colonies for a given-sized opening is determined, and from this the total number on the plate is calculated. The above method of examination gives approxi- mately the number of bacteria which are present in a Fig. 610. — Counter for Esmarch 's Roll-tube Cultures. water, and to some extent information as to the kind of bacteria. It is of great value, therefore, in con- trolling the work done by the water filters. In order to ascertain the presence of pathogenic and other bacteria special methods must be resorted to. The method which has been employed during a number of years in the Hygienic Laboratory of the University of .Michigan consists in planting a cubic centimeter and a drop of the water in tubes of bouillon, which are then incubated at 39° C. If no growth forms, as often is the case, pathogenic bacteria may be said to be excluded. When a growth does form, a portion (1 e.c.) is injected into a guinea-pig. In ease the animal dies the heart blood is examined for the kind of organism present. If no ill effects follow the injec- Fio. 611 - 1 itation Tube. tion, the watei maj be aid i<> !»■ free from pathogenic 'Ha. Sewage contamination Is u ually Indicated by the presence of colon bacilli and ol tn ptococci. presence i,t t lie former i • te ted i u bj mean "ft he Smith fermentation tube (1 is 61 I ater is added to glui ose bouillon in t In- fermental ion : which is then set aside at :;? C. The formatio gas indicates the probable dp sence of tin- colon Bacillus, while the non-production of gas points to the ab ence of t his organism. 1 url hi for indent ifical ton. Litmus-lactose agar plates should be mad.' directly from the water and also from the fei atation tube when gas production is present. The formation of red colonii ttive of the colon bacillus, i i.i organi m ferments lac- erea tj phoii i like I iactei ia do not. For the same purpose lac tose bouillon is some! imes empli 13 ei 1 in the fermenl ation tul ie. Another procedure is to plant 1 he water in carbolic bouillon, or in Parietti's solution, in order to elim- inate many of the more common iria. Neutral red bouillon and agar are also used for cultivating the sua pected colon bacillus. The water may be planted direct, or the red colonies which form On the plate may be used for inoculation. Some of the special media such as Endo's fuchsin agar, Harri- son's oesculin bile salt agar, etc., may be Used', with good results, by the plating method. Jackson's lactose bile medium is highly recommended by some water analysts. The coagulation of milk and the production of the indol reaction are additional tests of identification. F. ('.. Now. Revised by L. W. I'amui.exer. Bacteriolysis. — Under certain circumstances bac- teria are dissolved. This process is called bacterioly- sis and the substances which bring it about are termed bacteriolysins. Bacteriolysis may be a sort of self-digestion, brought about, according to some authorities, by a ferment contained within the cell, an endotryptase. Bacteri- olysis occurring in this manner is known as autolysis. Autolysis takes place only when the conditions are unfavorable for the growth and development of the organisms. For instance pneumococci will grow vig- orously for a time when planted in a suitable medium, but after a few days they gradually disappear leaving few or no traces. This disappearance is due to the fact that the cocci have been injured by the accumu- lation in the medium of their waste products and have then undergone lysis. If the temperature is too high or too low or in the presence of mild disinfectants such as chloroform, toluol, thymol, or salicylic acid, autolysis readily occurs. If, how- ever, the heat is too great or if the disinfectant added is too strong, such as would be the case with phenol or corrosive sublimate, then the ferment also is injured and autolysis is prevented. Even in physiological sail solution a certain amount of autolysis occurs, due probably to the insufficiency of food material. Bacteriolysis may result from the action of added substances, so-called chemical bacteriolysins. Alka- lies, antiformin, strong salt solutions, bile salts, cobra venom, and oleic acid belong to this group of chemical agents. There is a very great difference in the way the different organisms read to these lysins. The pneumococcus yields with comparative ease while the tubercle bacillus is unaffected even when treated with strong alkalies or antiformin. The true menin- gococcus is dissolved by bile and by taurocholic acid while the Jager meningococcus and the pus cocci are 927 Bacteriolysis REFERENCE HANDBOOK OF THE MEDICAL SCIENCES Bacteriuria not affected. Glycerin acts upon many bacteria but not upon the protozoa or the filterable viruses. In ral spores are the most resistant to bacteriolysis, with the acid-fast and Gram positive bacteria ranking next. The Gram negative organisms are the most susceptible. A notable exception is the pneumococ- cus which, although Gram positive, is very susceptible to most bacteriolytic agents. The reaction of bacteria to the lytic action of the digestive ferments differs somewhat from both of the above varieties of bacteriolysis. The living cells are attacked to a very slight degree if at all. When killed, the different varieties react in different ways. The Gram negative bacteria, when killed by a tem- perature of 75°-S0° C, are readily digested by artificial gastric juice and even more readily by trypsin. When killed by the weaker disinfectants such as chloroform, however, this digestion takes place to a much less marked degree. The Gram positive bacteria are much more resistant, many not being attacked by trypsin, even if they have been killed. Many normal sera possess a certain amount of bacteriolytic power which is more or less specific but which is capable of action on a fairly large number of organisms. When, however, an animal is inoculated with bacteria, specific bacteriolysins may be produced in large quantities. Specific bacteriolysins are anti- bodies of Ehrlich's third order and are much more com- plicated than the bodies of the first and second orders. They are amboceptors, relatively thermostabile and require the presence of complement for their action. Their manner of action is analogous to that of all the cytolysins. Bacteriolysis was first described by Pfeiffer who demonstrated the process by the aid of the following experiment: Two guinea pigs, one normal and one immunized were injected intraperitoneally with living cholera vibrios. The peritoneal exudate was with- drawn from time to time and examined. While the cholera vibrios in the peritoneal exudate of the normal animal were unaffected and the animal suc- cumbed to the infection, those in the exudate of the immunized animal behaved very differently. They first began to lose in motility, then broke up into small granules, and finally disappeared and the animal recovered. He later found that the same lytic power was present in the serum of the immunized animal. Bacteriolysis thus constitutes one of the important defenses of the body against infection. The process however is not without danger to the animal. If there are a large number of bacteria present in the blood when a dose of bacteriolytic serum is admin- istered, their sudden lysis may result in the setting free of a large quantity of endotoxin which may be powerful enough to cause death even though the in- fection itself has been cured. At might be supposed from the behaviour of bacteria to other bacteriolytic agents, not all the organisms are able to stimulate an animal to the production of bacteriolysins. For such as are thus able, however, the bacteriolytic serum con- stitutes a much more real immunity than the anti- toxic immunity produced as a result of the inoculation of other bacteria. It is easily seen that a, serum which contains merely substances which neutralize bacterial poisons may leave unharmed in the body the organ- isms which produced the toxins and these bacteria may later develop again into virulent forms. Because of the difficulty in their production, however, bacterioly- tic sera are not in very general use. The bacterioly- sis which takes place in serum whether or not it con- tains specific bacteriolysins, has proven an attractive subject around which have collected many theories. TIm' nature of the complement, the role of the leuco- cyte, the question as to the part played by the lipoids, all these are closely connected with the main problem, and about them we know practically nothing. In the article on Immunity the reader will find a more de- tailed discussion than is possible here. Ralph G. Stillman. Bacteriotropins. — Wright observed that among the antibodies which were produced by an animal which had been inoculated with bacteria were some which rendered the bacteria in question more susceptible of phagocytosis. These bodies he called opsonins. He recognized the fact that there were opsonins resi- dent in normal sera and that they were less specific than the immune opsonins. Neufeld, however, found that the immune opsonins were much more thermos- tabile than the normal opsonins and came to the con- clusion that they were entirely different substances. To the immune opsonins he gave the name bacterio- tropins. Bacteriotropins exert their influence en- tirely upon the bacteria, for if a bacterial emulsion be mixed with a serum containing these substances and then centrifuged to remove the serum the bacteria will be found to be more readily subject to phagocy- tosis than organisms not so treated. Their nature is unknown. There has been an effort to identify them with the antiaggressins of Bail but not on sound experimental grounds. Their importance in im- munity is obvious, as a serum of high bacteriotropic value would sensitize a large number of organisms and thus virtually enormously increase the power of the leucocytes to destroy them. The technique of determining the bacteriotropic power of a serum is identical with that of obtaining the opsonic index, for which the reader is referred to the article on Opsonins. The relation of these bodies to the other antibodies will be discussed in detail in the article on Immunity. Ralph G. Stillman. Bacterium. — A genus of the family Bacteria* / , containing cylindrical rod-shaped or ellipsoidal organisms, without flagella, sometimes with endo- spores, and often grouped in zoogleea masses. The genus is not well defined, many of the species being classed by some bacteriologists among the bacilli; Bad. coli, for example, being more commonly called Bacillus coli communis, and Bad. influenza;, B. in- fluenza. Bad. termo is a collective term now practi- cally obsolute, applied to a number of the putre- factive bacteria. The term bacteria (the plural form of bacterium) is also commonly employed in a general sense as synonymous with Schizomycetes, or the fusion-fungi. T. L. S. Bacteriuria. — If a urine is rich in bacterial content when it is voided, the subject is said to suffer from bacteriuria. The clinical evidence of this condition is usually held to be a turbidity which cannot be made to disappear by filtration, centrifuging, warming, or the addition of acids or alkalies. The claim has been made, however, that bacteriuria may be present with clear urine. Under the microscope a drop of the fluid is seen to be swarming with bacilli and cocci in a state of rapid movement. The turbidity can be made to clear up by agitation with barium carbonate and filtration through asbestos. The reaction in bacte- riuria may be acid or alkaline, and the urine rapidly undergoes either the alkaline or acid fermentation. The condition is an expression of some purulent affec- tion at some point in the urogenital tract, of hem- atogenous infections of the kidneys (scarlatinal neph- ritis), and certain systemic affections — diabetes, Weil's disease. The bacterial flora show a wide range, but are doubtless for the most part saprophytes. E. P. END OF VOLUME I. 928 II I I II D 000 207 268 4 W 13 R332 1913 v.l A Reference handbook of the medical sciences. MEDICAL SCIENCES LIBRARY UNIVERSITY OF CALIFORNIA, IRVINE IRVINE, CALIFORNIA 92664